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June 19, 2019
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https://www.sciencedaily.com/releases/2019/06/190619134832.htm
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Scientists chart course toward a new world of synthetic biology
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Genetically engineered trees that provide fire-resistant lumber for homes. Modified organs that won't be rejected. Synthetic microbes that monitor your gut to detect invading disease organisms and kill them before you get sick.
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These are just some of the exciting advances likely to emerge from the 20-year-old field of engineering biology, or synthetic biology, which is now mature enough to provide solutions to a range of societal problems, according to a new roadmap released today (June 19) by the Engineering Biology Research Consortium, a public-private partnership partially funded by the National Science Foundation and centered at the University of California, Berkeley.The roadmap is the work of more than 80 scientists and engineers from a range of disciplines, representing more than 30 universities and a dozen companies. While highly technical, the report provides a strong case that the federal government should invest in this area, not only to improve public health, food crops and the environment, but also to fuel the economy and maintain the country's leadership in synthetic biology. The report comes out in advance of the year's major technical conference for synthetic biology, 2019 Synthetic Biology: Engineering, Evolution & Design, which takes place June 23-27 in New York City.Engineering biology/synthetic biology encompasses a broad range of current endeavors, including genetically modifying crops, engineering microbes to produce drugs, fragrances and biofuels, editing the genes of pigs and dogs using CRISPR-Cas9, and human gene therapy. But these successes are just a prelude to more complex biological engineering coming in the future, and the report lays out the opportunities and challenges, including whether or not the United States makes it a research priority."The question for government is, if all of these avenues are now open for biotechnology development, 'How does the U.S. stay ahead in those developments as a country?'" said Douglas Friedman, one of the leaders of the roadmap project and executive director of the Engineering Biology Research Consortium. "This field has the ability to be truly impactful for society, and we need to identify engineering biology as a national priority, organize around that national priority and take action based on it."China and the United Kingdom have made engineering biology/synthetic biology -- which means taking what we know about the genetics of plants and animals and then tweaking specific genes to make these organisms do new things -- a cornerstone of their national research enterprise.Following that lead, the U.S. House of Representatives held a hearing in March to discuss the Engineering Biology Research and Development Act of 2019, a bill designed to "provide for a coordinated federal research program to ensure continued United States leadership in engineering biology." This would make engineering biology a national initiative equivalent to the country's recent commitments to quantum information systems and nanotechnology."What this roadmap does and what all of our collaborators on this project have done is to imagine, over the next 20 years, where we should go with all of this work," said Emily Aurand, who directed the roadmapping project for the EBRC. "The goal was to address how applications of the science can expand very broadly to solve societal challenges, to imagine the breadth and complexity of what we can do with biology and biological systems to make the world a better, cleaner, more exciting place.""This roadmap is a detailed technical guide that I believe will lead the field of synthetic biology far into the future. It is not meant to be a stagnant document, but one that will continually evolve over time in response to unexpected developments in the field and societal needs." said Jay Keasling, a UC Berkeley professor of chemical and biomolecular engineering and the chair of EBRC's roadmapping working group.The roadmap would guide investment by all government agencies, including the Department of Energy, Department of Defense and National Institutes of Health as well as NSF."The EBRC roadmap represents a landmark achievement by the entire synthetic biology and engineering biology community," said Theresa Good, who is the deputy division director for molecular and cellular biosciences at the National Science Foundation and co-chair of a White House-level synthetic biology interagency working group. "The roadmap is the first U.S. science community technical document that lays out a path to achieving the promise of synthetic biology and guideposts for scientists, engineers and policy makers to follow."Some products of engineering biology are already on the market: non-browning apples; an antimalarial drug produced by bacteria; corn that produces its own insecticide. One Berkeley start-up is engineering animal cells to grow meat in a dish. An Emeryville start-up is growing textiles in the lab. A UC Berkeley spin off is creating medical-quality THC and CBD, two of the main ingredients in marijuana, while another is producing brewer's yeast that provide the hoppy taste in beer, but without the hops.But much of this is still done on small scales; larger-scale projects lie ahead. UC Berkeley bioengineers are trying to modify microbes so that they can be grown as food or to produce medicines to help humans survive on the moon or Mars.Others are attempting to engineer the microbiome of cows and other ruminants so that they can better digest their feed, absorb more nutrients and produce less methane, which contributes to climate change. With rising temperatures and less predictable rain, scientists are also trying to modify crops to better withstand heat, drought and saltier soil.And how about modified microbes, seaweed or other ocean or freshwater plants -- or even animals like mussels -- that will naturally remove pollutants and toxins from our lakes and ocean, including oil and plastic?"If you look back in history, scientists and engineers have learned how to routinely modify the physical world though physics and mechanical engineering, learned how to routinely modify the chemical world through chemistry and chemical engineering," Friedman said. "The next thing to do is figure out how to utilize the biological world through modifications that can help people in a way that would otherwise not be possible. We are at the precipice of being able to do that with biology."While in the past some genetically engineered organisms have generated controversy, Friedman says the scientific community is committed to engaging with the public before their introduction."It is important that the research community, especially those thinking about consumer-facing products and technologies, talk about the ethical, legal and societal implications early and often in a way different than we have seen with biotech developments in the past," he said.In fact, the benefits of engineering biology are so vast that it's an area we just cannot ignore."The opportunity is immense," Friedman said.Report:
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Genetically Modified
| 2,019 |
June 10, 2019
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https://www.sciencedaily.com/releases/2019/06/190610111557.htm
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Ancient DNA from Roman and medieval grape seeds reveal ancestry of wine making
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A grape variety still used in wine production in France today can be traced back 900 years to just one ancestral plant, scientists have discovered.
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With the help of an extensive genetic database of modern grapevines, researchers were able to test and compare 28 archaeological seeds from French sites dating back to the Iron Age, Roman era, and medieval period.Utilising similar ancient DNA methods used in tracing human ancestors, a team of researchers from the UK, Denmark, France, Spain, and Germany, drew genetic connections between seeds from different archaeological sites, as well as links to modern-day grape varieties.It has long been suspected that some grape varieties grown today, particularly well-known types like Pinot Noir, have an exact genetic match with plants grown 2,000 years ago or more, but until now there has been no way of genetically testing an uninterrupted genetic lineage of that age.Dr Nathan Wales, from the University of York, said: "From our sample of grape seeds we found 18 distinct genetic signatures, including one set of genetically identical seeds from two Roman sites separated by more than 600km, and dating back 2,000 years ago."These genetic links, which included a 'sister' relationship with varieties grown in the Alpine regions today, demonstrate winemakers' proficiencies across history in managing their vineyards with modern techniques, such as asexual reproduction through taking plant cuttings."One archaeological grape seed excavated from a medieval site in Orléans in central France was genetically identical to Savagnin Blanc. This means the variety has grown for at least 900 years as cuttings from just one ancestral plant.This variety (not to be confused with Sauvignon Blanc), is thought to have been popular for a number of centuries, but is not as commonly consumed as a wine today outside of its local region.The grape can still be found growing in the Jura region of France, where it is used to produce expensive bottles of Vin Jaune, as well as in parts of Central Europe, where it often goes by the name Traminer.Although this grape is not so well known today, 900 years of a genetically identical plant suggests that this wine was special -- special enough for grape-growers to stick with it across centuries of changing political regimes and agricultural advancements.Dr Jazmín Ramos-Madrigal, a postdoctoral researcher from the University of Copenhagen, said: "We suspect the majority of these archaeological seeds come from domesticated berries that were potentially used for winemaking based on their strong genetic links to wine grapevines."Berries from varieties used for wine are small, thick-skinned, full of seeds, and packed with sugar and other compounds such as acids, phenols, and aromas -- great for making wine but not quite as good for eating straight from the vine. These ancient seeds did not have a strong genetic link to modern table grapes."Based on writings by the Roman author and naturalist, Pliny the Elder, and others, we know the Romans had advanced knowledge of winemaking and designated specific names to different grape varieties, but it has so far been impossible to link their Latin names to modern varieties."Now we have the opportunity to use genetics to know exactly what the Romans were growing in their vineyards."Of the Roman seeds, the researchers could not find an identical genetic match with modern-day seeds, but they did find a very close relationships with two important grape families used to produce high quality wine.These include the Syrah-Mondeuse Blanche family -- Syrah is one of the most planted grapes in the world today -- and the Mondeuse Blanche, which produces a high quality AOC (protected regional product) wine in Savoy, as well as the Pinot-Savagnin family -- Pinot Noir being the "king of wine grapes."Dr Wales said: "It is rather unconventional to trace an uninterrupted genetic lineage for hundreds of years into the past. Instead of exploring broad patterns in genetic ancestry, as in most ancient DNA projects, we had to think like forensics scientists and find a perfect match in the database."Large databases of genetic data from modern crops and optimized palaeogenomic methods have vastly improved our ability to analyse the history of this and other important fruits."For the wine industry today, these results could shed new light on the value of some grape varieties; even if we don't see them in popular use in wines today, they were once highly valued by past wine lovers and so are perhaps worth a closer look."The researchers now hope to find more archaeological evidence that could send them further back in time and reveal more grape wine varieties.The research is funded by the Danish Council for Independent Research, the Danish National Research Foundation, and the French National Agency of Research, and published in
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Genetically Modified
| 2,019 |
June 4, 2019
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https://www.sciencedaily.com/releases/2019/06/190604131137.htm
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Would you eat genetically modified food if you understood the science behind it?
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Jonathon McPhetres, a newly minted PhD in psychology from the University of Rochester, admits he's "personally amazed" what we can do with genes, specifically genetically modified food -- such as saving papayas from extinction.
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"We can makes crops better, more resilient, and more profitable and easier for farmers to grow, so that we can provide more crops around the world," he says.Yet the practice of altering foods genetically, through the introduction of a gene from a different organism, has courted controversy right from the get-go. While genetically modified organisms (GMOs) are considered safe by an overwhelming majority of scientists, including the National Academy of Sciences, the World Health Organization, and the American Medical Association, only about one third of consumers share that view.One reason for the divide is that critics of genetically modified food have been vocal, often decrying it as "unnatural" or "Frankenfood" -- in stark contrast to a 2016 review of published research that found no convincing evidence for negative health or environmental effects of GM foods.A team of psychologists and biologists from the University of Rochester, the University of Amsterdam in the Netherlands, and Cardiff University in Wales, set out to discover if the schism could be overcome; that is, to see if consumers' attitudes would change if the public understood the underlying science better.The short answer is "yes." The team's findings were recently published in the "Political orientation and demographics inform attitudes and we can't change those," says McPhetres, the study's lead author. "But we can teach people about the science behind GMOs, and that seems to be effective in allowing people to make more informed decisions about the products that they use or avoid."Previous research has shown that more than half of Americans know very little or nothing at all about GM foods.In a series of studies, the team discovered that people's existing knowledge about GM food is the greatest determining factor of their attitudes towards the food -- overriding all other tested factors. In fact, existing GM knowledge was more than 19 times higher as a determinant -- compared to the influence of demographic factors such as a person's education, socioeconomic status, race, age, and gender.The team replicated the US findings in the United Kingdom and the Netherlands, where opposition to modified food has tended to be higher than in the United States, and where GM food is highly regulated in response to consumer concerns.In one study, using a representative US sample, participants responded on a scale of 1 (don't care if foods have been genetically modified), 2 (willing to eat, but prefer unmodified foods), to 3 (will not eat genetically modified foods). Next, the team asked 11 general science knowledge questions -- such as whether the universe began with a huge explosion, antibiotics kill viruses as well as bacteria, electrons are smaller than atoms, and how long it takes for the earth to orbit the sun. In study 2, participants took an additional quiz about their knowledge about the science, methods, and benefits of GM foods and procedures.The team found that specific knowledge about GM foods and procedures is independent from a person's general science knowledge -- making the first (GM knowledge) a nearly twice as strong predictor of GM attitudes.The researchers followed up by conducting a five-week longitudinal study with 231 undergraduates in the US to test, first, if a lack of knowledge about GM foods could be overcome by teaching participants the basic science behind GM technology, and second, if greater knowledge would alter attitudes. McPhetres worked with Rochester colleague Jennifer Brisson, an associate biology professor, who vetted the students' learning materials.The team discovered that learning the underlying science led to more positive attitudes towards genetically modified foods, a greater willingness to eat them, and a lowered perception of GM foods as risky.Their findings, argues the team, lend direct support for the deficit model of science attitudes, which -- in broad terms -- holds that the public's skepticism towards science and technology is largely due to a lack of understanding, or absence of pertinent information.The team's online modules avoid confrontational approaches "which threaten preexisting beliefs and convictions," suggesting a relatively simple guide for how to overcome skepticism about GM foods: focus on the actual underlying science not the message.For McPhetres, the studies tie neatly into his larger research focus on people's basic science knowledge and general interest in science -- and how to improve both.Knowledge and appreciation of science -- "that's the kind of information that people need to make informed decisions about products they use, and the food they eat," say McPhetres who's now heading to Canada for a joint post-doctoral appointment between the University of Regina in Saskatchewan, and the Massachusetts Institute of Technology.
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Genetically Modified
| 2,019 |
May 30, 2019
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https://www.sciencedaily.com/releases/2019/05/190530141501.htm
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Transgenic fungus rapidly killed malaria mosquitoes in West African study
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According to the World Health Organization, malaria affects hundreds of millions of people around the world, killing more than 400,000 annually. Decades of insecticide use has failed to control mosquitoes that carry the malaria parasite and has led to insecticide-resistance among many mosquito strains. In response, scientists began genetically modifying mosquitoes and other organisms that can help eradicate mosquitoes. Until now, none of these transgenic approaches made it beyond laboratory testing.
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In a research paper published in the May 31, 2019, issue of the journal "No transgenic malaria control has come this far down the road toward actual field testing," said Brian Lovett, a graduate student in UMD's Department of Entomology and the lead author of the paper. "This paper marks a big step and sets a precedent for this and other transgenic methods to move forward.""We demonstrated that the efficacy of the transgenic fungi is so much better than the wild type that it justifies continued development," said Raymond St. Leger, a Distinguished University Professor of Entomology at UMD and co-author of the study.The fungus is a naturally occurring pathogen that infects insects in the wild and kills them slowly. It has been used to control various pests for centuries. The scientists used a strain of the fungus that is specific to mosquitoes and engineered it to produce a toxin that kills mosquitoes more rapidly than they can breed. This transgenic fungus caused mosquito populations in their test site to collapse to unsustainable levels within two generations."You can think of the fungus as a hypodermic needle we use to deliver a potent insect-specific toxin into the mosquito," said St. Leger.The toxin is an insecticide called Hybrid. It is derived from the venom of the Australian Blue Mountains funnel-web spider and has been approved by the Environmental Protection Agency (EPA) for application directly on crops to control agricultural insect pests."Simply applying the transgenic fungus to a sheet that we hung on a wall in our study area caused the mosquito populations to crash within 45 days," Lovett said. "And it is as effective at killing insecticide-resistant mosquitoes as non-resistant ones."Lovett said laboratory tests suggest that the fungus will infect the gamut of malaria-carrying mosquitoes. The abundance of species that transmit malaria has hindered efforts to control the disease, because not all species respond to the same treatment methods.To modify the fungus Metarhizium pingshaense so that it would produce and deliver Hybrid, the University of Maryland research team used a standard method that employs a bacterium to intentionally transfer DNA into fungi. The DNA the scientists designed and introduced into the fungi provided the blueprints for making Hybrid along with a control switch that tells the fungus when to make the toxin.The control switch is a copy of the fungus' own DNA code. Its normal function is to tell the fungus when to build a defensive shell around itself so that it can hide from an insect's immune system. Building that shell is costly for the fungus, so it only makes the effort when it detects the proper surroundings -- inside the bloodstream of a mosquito.By combining the genetic code for that switch with the code for making Hybrid, the scientists were able to ensure that their modified fungus only produces the toxin inside the body of a mosquito. They tested their modified fungus on other insects in Maryland and Burkina Faso, and found that the fungus was not harmful to beneficial species such as honeybees."These fungi are very selective," St. Leger said. "They know where they are from chemical signals and the shapes of features on an insect's body. The strain we are working with likes mosquitoes. When this fungus detects that it is on a mosquito, it penetrates the mosquito's cuticle and enters the insect. It won't go to that trouble for other insects, so it's quite safe for beneficial species such as honeybees."After demonstrating the safety of their genetically modified fungus in the lab, Lovett and St. Leger worked closely with scientific colleagues and government authorities in Burkina Faso to test it in a controlled environment that simulated nature. In a rural, malaria-endemic area of Burkina Faso, they constructed a roughly 6,550-square-foot, screened-in structure they called MosquitoSphere. Inside, multiple screened chambers contained experimental huts, plants, small mosquito-breeding pools and a food source for the mosquitoes.In one set of experiments, the researchers hung a black cotton sheet coated with sesame oil on the wall of a hut in each of three chambers. One sheet received oil mixed with the transgenic fungus Metarhizium pingshaense, one received oil with wild-type Metarhizium and one received only sesame oil. Then, they released 1,000 adult male and 500 adult female mosquitoes into each chamber of MosquitoSphere to establish breeding populations. The researchers then counted mosquitoes in each chamber every day for 45 days.In the chamber containing the sheet treated with the transgenic fungus, mosquito populations plummeted over 45 days to just 13 adult mosquitoes. That is not enough for the males to create a swarm, which is required for mosquitoes to breed. By comparison, the researchers counted 455 mosquitoes in the chamber treated with wild-type fungus and 1,396 mosquitoes in the chamber treated with plain sesame oil after 45 days. They ran this experiment multiple times with the same dramatic results.In similar experiments in the lab, the scientists also found that females infected with transgenic fungus laid just 26 eggs, only three of which developed into adults, whereas uninfected females laid 139 eggs that resulted in 74 adults.According to the researchers, it is critically important that new anti-malarial technologies, such as the one tested in this study, are easy for local communities to employ. Black cotton sheets and sesame oil are relatively inexpensive and readily available locally. The practice also does not require people to change their behavior, because the fungus can be applied in conjunction with pesticides that are commonly used today."By following EPA and World Health Organization protocols very closely, working with the central and local government to meet their criteria and working with local communities to gain acceptance, we've broken through a barrier," Lovett said. "Our results will have broad implications for any project proposing to scale up new, complex and potentially controversial technologies for malaria eradication."Next, the international team of scientists hope to test their transgenic fungus in a local village or community. There are many regulatory and social benchmarks to meet before deploying this new method in an open environment such as a village, but the researchers said this study helps make the case for such trials.
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Genetically Modified
| 2,019 |
May 28, 2019
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https://www.sciencedaily.com/releases/2019/05/190528140106.htm
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New genetic engineering strategy makes human-made DNA invisible
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Bacteria are everywhere. They live in the soil and water, on our skin and in our bodies. Some are pathogenic, meaning they cause disease or infection. To design effective treatments against pathogens, researchers need to know which specific genes are to blame for pathogenicity.
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Scientists can identify pathogenic genes through genetic engineering. This involves adding human-made DNA into a bacterial cell. However, the problem is that bacteria have evolved complex defense systems to protect against foreign intruders -- especially foreign DNA. Current genetic engineering approaches often disguise the human-made DNA as bacterial DNA to thwart these defenses, but the process requires highly specific modifications and is expensive and time-consuming.In a paper published recently in the Johnston is a researcher in the Vaccine and Infectious Disease Division at the Fred Hutchinson Cancer Research Center and lead author of the paper. He said that when a bacterial cell detects it has been penetrated by foreign DNA, it quickly destroys the trespasser. Bacteria live under constant threat of attack by a virus, so they have developed incredibly effective defenses against those threats.The problem, Johnston explained, is that when scientists want to place human-made DNA into bacteria, they confront the exact same defense systems that protect bacteria against a virus.To get past this barrier, scientists add specific modifications to disguise the human-made DNA and trick the bacterium into thinking the intruder is a part of its own DNA. This approach sometimes works but can take considerable time and resources.Johnston's strategy is different. Instead of adding a disguise to the human-made DNA, he removes a specific component of its genetic sequence called a motif. The bacterial defense system needs this motif to be present to recognize foreign DNA and mount an effective counter-attack. By removing the motif, the human-made DNA becomes essentially invisible to the bacterium's defense system."Imagine a bacterium like an enemy submarine in a dry-dock, and a human-made genetic tool as your soldier that needs to get inside the submarine to carry out a specific task. The current approaches would be like disguising the spy as an enemy soldier, having them walk up to each gate, allowing the guards to check their credentials, and if all goes well, they're in," Johnston said. "Our approach is to make that soldier invisible and have them sneak straight through the gates, evading the guards entirely."This new method requires less time and fewer resources than current techniques. In the study, Johnston used Staphylococcus aureus bacteria as a model, but the underlying strategy he developed can be used to sneak past these major defense systems that exist in 80 to 90 percent of bacteria that are known today.This new genetic engineering tool opens up the possibilities for research on bacteria that haven't been well studied before. Since scientists have a limited amount of time and resources, they tend to work with bacteria that have already been broken into, Johnston explained. With this new tool, a major barrier to breaking into bacteria DNA has been solved, and researchers can use the method to engineer more clinically relevant bacteria."Bacteria are the drivers of our planet," said Dr. Gary Borisy, a Senior Investigator at the Forsyth Institute and co-author of the paper. "The capacity to engineer bacteria has profound implications for medicine, for agriculture, for the chemical industry, and for the environment."This research was facilitated by an 'NIH Director's Transformative Research Award' (R01OD024734) granted to the research team in 2017 through the National Institute of Dental and Craniofacial Research (NIDCR).
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Genetically Modified
| 2,019 |
May 23, 2019
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https://www.sciencedaily.com/releases/2019/05/190523130203.htm
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Engineered bacteria could be missing link in energy storage
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One of the big issues with sustainable energy systems is how to store electricity that's generated from wind, solar and waves. At present, no existing technology provides large-scale storage and energy retrieval for sustainable energy at a low financial and environmental cost.
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Engineered electroactive microbes could be part of the solution; these microbes are capable of borrowing an electron from solar or wind electricity and using the energy to break apart carbon dioxide molecules from the air. The microbes can then take the carbon atoms to make biofuels, such as isobutanol or propanol, that could be burned in a generator or added to gasoline, for example."We think biology plays a significant role in creating a sustainable energy infrastructure," said Buz Barstow, assistant professor of biological and environmental engineering at Cornell University. "Some roles will be supporting roles and some will be major roles, and we're trying to find all of those places where biology can work."Barstow is the senior author of "Electrical Energy Storage With Engineered Biological Systems," published in the Adding electrically engineered (synthetic or non-biological) elements could make this approach even more productive and efficient than microbes alone. At the same time, having many options also creates too many engineering choices. The study supplies information to determine the best design based on needs."We are suggesting a new approach where we stitch together biological and non-biological electrochemical engineering to create a new method to store energy," said Farshid Salimijazi, a graduate student in Barstow's lab and the paper's first author.Natural photosynthesis already offers an example for storing solar energy at a huge scale, and turning it into biofuels in a closed carbon loop. It captures about six times as much solar energy in a year as all civilization uses over the same time. But, photosynthesis is really inefficient at harvesting sunlight, absorbing less than one percent of the energy that hits photosynthesizing cells.Electroactive microbes let us replace biological light harvesting with photovoltaics. These microbes can absorb electricity into their metabolism and use this energy to convert CO2 to biofuels. The approach shows a lot of promise for making biofuels at higher efficiencies.Electroactive microbes also allow for the use of other types of renewable electricity, not just solar electricity, to power these conversions. Also, some species of engineered microbes may create bioplastics that could be buried, thereby removing carbon dioxide (a greenhouse gas) from the air and sequestering it in the ground. Bacteria could be engineered to reverse the process, by converting a bioplastic or biofuel back to electricity. These interactions can all occur at room temperature and pressure, which is important for efficiency.The authors point out that non-biological methods for using electricity for carbon fixation (assimilating carbon from CO2 into organic compounds, such as biofuels) are starting to match and even exceed microbes' abilities. However, electrochemical technologies are not good at creating the kinds of complex molecules necessary for biofuels and polymers. Engineered electroactive microbes could be designed to convert these simple molecules into much more complicated ones.Combinations of engineered microbes and electrochemical systems could greatly exceed the efficiency of photosynthesis. For these reasons, a design that marries the two systems offers the most promising solution for energy storage, according to the authors."From the calculations that we have done, we think it's definitely possible," Salimijazi said.The paper includes performance data on biological and electrochemical designs for carbon fixation. The current study is "the first time that anybody has gathered in one place all of the data that you need to make an apples-to-apples comparison of the efficiency of all these different modes of carbon fixation," Barstow said.In the future, the researchers plan to use the data they have assembled to test out all possible combinations of electrochemical and biological components, and find the best combinations out of so many choices.The study was supported by Cornell and the Burroughs-Wellcome Fund.
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Genetically Modified
| 2,019 |
May 21, 2019
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https://www.sciencedaily.com/releases/2019/05/190521162437.htm
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Developing biosecurity tool to detect genetically engineered organisms in the wild
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If a genetically or synthetically engineered organism is released into the environment, how will we know? How can we tell it apart from the millions of microorganisms that exist naturally in the wild? That's the challenge being taken on by a multi-institution research team, including Eric Young, assistant professor of chemical engineering at Worcester Polytechnic Institute (WPI), that is developing a biosecurity tool that can detect engineered microorganisms based on their unique DNA signatures.
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Genetic engineering, in which genes are added to the genomes of organisms, and synthetic biology, which focuses on understanding and designing better DNA sequences, are both used today to make a wide array of products, such as pharmaceuticals, like insulin, and agricultural crops. Genetic engineering also is used by biotechnology companies -- from start-ups to multinational corporations -- to manufacture products like detergents, food ingredients, and biofuels.For decades, the U.S. government has sponsored research on and development of engineered organisms and better ways to design DNA, while the government and the synthetic biology community have worked together to develop safety and ethical practices to ensure the organisms that are made are safe and can be contained. For example, the government has sponsored the development of "kill switches" that make it impossible for engineered organisms to survive outside the lab.Recently, the U.S. government and research scientists have identified a need for new tools that can identify engineered organisms when they are mixed in with a myriad of naturally occurring microorganisms. These tools could eventually be deployed to detect engineered organisms in the environment. They could be used to protect a company's intellectual property should an organism it designed accidentally escape the lab or to detect intentional releases of potentially harmful organisms.This is the task being taken on by the multi-institutional team charged with developing such a tool. The project is funded by an 18-month award from the Finding Engineering Linked Indicators (FELIX) program, which is run through Intelligence Advanced Research Projects Activity (IARPA), an organization within the Office of the Director of National Intelligence that funds research to address challenges facing the U.S. intelligence community. The award has a second phase that could be renewed for an additional 24 months. Raytheon, a Massachusetts-based defense contractor, is the primary contractor; Young, who has received a $377,746 award for his part of the project, is one of five subcontractors. The others are Johns Hopkins University, Princeton University, University of California at San Francisco, and Mission Bio, a San Francisco-based biotech company."We realize the power of engineering and bioengineering," said Young, whose expertise is in synthetic biology, including the genetic engineering of bacteria, yeast, and fungi. "We are excited about the promise of synthetic biology, but we also have an ethical responsibility to think about the potentially negative uses of the technologies we develop."My lab is developing engineered organisms to solve problems, and we use safety practices beyond what we are required to use," he added. "Hopefully, this project will lead us to a low-cost tool that we can use to make sure everyone is working to prevent the release of organisms into the environment, from universities to manufacturing plants to DIY bio enthusiasts in their garages."Scientists create engineered microorganisms by introducing new genes into their genomes that enable them to produce valuable drugs, biofuels, or food products. A bacterium containing the human gene for producing insulin, or a yeast bearing multiple genes from several organisms to make the antimalarial drug artemisinin are examples. Because many of the genes in these engineered organisms exist in nature, telling them apart from non-engineered organisms in soil or water samples can be challenging. "It's akin to finding the proverbial needle in a haystack," Young said.He added that the key to making that distinction will be identifying genetic signatures for each organism. By virtue of the way they are produced, the majority of genetically engineered organisms have one or more short sections of DNA that are unique to their genomes and make them different from their non-engineered cousins. These DNA signatures can be used as markers to quickly spot an engineered organism in a population of naturally occurring microorganisms. Young's role in the research project is to generate examples of bioengineered organisms that contain these specific markers."We are supplying the 'expert' information the detection device will look for," he said. "We are taking into account the genetic engineering of the past 50 years and reducing all of that knowledge and information down to a set of essential signatures for bioengineered organisms that we would most likely need to find. It's up to our sponsor and the team to decide which organisms are important, and we help decide what signatures we have to look at. It's very exciting work."Initially, Young, who is working with two graduate students, will focus on brewer's yeast, which he says is increasingly becoming the organism-of-choice for bioengineering companies because it is easy to engineer and simple to grow, given the decades of large-scale fermentation experience in the brewing industry. The signatures he is identifying will be useful for detecting known engineered organisms that may have come from corporate and university labs. Detecting potentially harmful organisms that may have been intentionally released into the environment will be a greater challenge."It's a whole lot more complicated when you don't know what organisms you might need to look for," he said. "We have to think about what is most likely to be out there and what would somebody with limited resources create. We need to create tools that can detect a wide range of engineered organisms. And they need to be flexible enough that they could detect a specific set of signatures but then detect newly added signatures as they are found. We are helping develop a technology to do that."The knowledge Young is generating will ultimately be incorporated into a benchtop detection device that will be developed by other members of the research team. Other team members are creating machine learning algorithms that will find new signatures that experts may not identify. Young said he expects a usable detection device for yeast will be ready at the conclusion of the program, but it could be five to 10 years before the more complex challenges are solved.
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Genetically Modified
| 2,019 |
May 16, 2019
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https://www.sciencedaily.com/releases/2019/05/190516131738.htm
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Measuring plant improvements to help farmers boost production
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An international team is using advanced tools to develop crops that give farmers more options for sustainably producing more food on less land. To do this, thousands of plant prototypes must be carefully analyzed to figure out which genetic tweaks work best. Today, in a special issue of the journal
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"This method allows us to measure improvements we have engineered in a plant's photosynthesis machinery in about ten seconds, compared to the traditional method that takes up 30 minutes," Katherine Meacham-Hensold, a postdoctoral researcher at the University of Illinois, who led this work for a research project called Realizing Increased Photosynthetic Efficiency (RIPE). "That's a major advance because it allows our team to analyze an enormous amount of genetic material to efficiently pinpoint traits that could greatly improve crop performance."RIPE, which is led by Illinois, is engineering crops to be more productive by improving photosynthesis, the natural process all plants use to convert sunlight into energy and yield. RIPE is supported by the Bill & Melinda Gates Foundation, the U.S. Foundation for Food and Agriculture Research (FFAR), and the U.K. Government's Department for International Development (DFID).The traditional method for assessing photosynthesis analyzes the exchange of gases through the leaf; it provides a huge amount of information, but it takes 30 minutes to measure each leaf. A faster, or "higher-throughput" method, called spectral analysis, analyzes the light that is reflected back from leaves to predict photosynthetic capacity in as little as 10 seconds."The question we set out to answer is: can we apply spectral techniques to predict photosynthetic capacity when we have genetically altered the photosynthetic machinery," said RIPE research leader Carl Bernacchi, a scientist with the U.S. Department of Agriculture, Agricultural Research Service, who is based at Illinois' Carl R. Woese Institute for Genomic Biology. "Before this study, we didn't know if changing the plant's photosynthetic pathways would change the signal that is detected by spectral measurements."Although they can prove this method can be used to screen crops that have been engineered to improve photosynthesis, researchers have not uncovered what spectral analysis measures exactly. "Spectral analysis requires custom-built models to translate spectral data into measurements of photosynthetic capacity that must be recreated each year," Meacham said. "Our next challenge is to figure out what we are measuring so that we can build predictive models that can be used year after year to compare results over time.""While there are still hurdles ahead, spectral analysis is a game-changing technique that can be used to assess a variety of photosynthetic improvements to single out the changes that are most likely to substantially, and sustainably, increase crop yields," said RIPE executive committee member Christine Raines, a professor of plant molecular physiology at the University of Essex, whose engineered crops were analyzed with the technique. "These tools can help us speed up our efforts to develop high-yielding crops for farmers working to help feed the world."
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Genetically Modified
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May 15, 2019
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https://www.sciencedaily.com/releases/2019/05/190515085450.htm
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Chewing gums reveal the oldest Scandinavian human DNA
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The first humans who settled in Scandinavia more than 10,000 years ago left their DNA behind in ancient chewing gums, which are masticated lumps made from birch bark pitch. This is shown in a new study conducted at Stockholm University and published in
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There are few human bones of this age, close to 10,000 years old, in Scandinavia, and not all of them have preserved enough DNA for archaeogenetic studies. In fact, the DNA from these newly examined chewing gums is the oldest human DNA sequenced from this area so far. The DNA derived from three individuals, two females and one male, creates an exciting link between material culture and human genetics.Ancient chewing gums are as of now an alternative source for human DNA and possibly a good proxy for human bones in archaeogenetic studies. The investigated pieces come from Huseby-Klev, an early Mesolithic hunter-fisher site on the Swedish west coast. The sites excavation was done in the early 1990's, but at this time it was not possible to analyse ancient human DNA at all, let alone from non-human tissue. The masticates were made out of birch bark tar and used as glue in tool production and other types of technology during the Stone Age."When Per Persson and Mikael Maininen proposed to look for hunter-gatherer DNA in these chewing gums from Huseby Klev we were hesitant but really impressed that archaeologists took care during the excavations and preserved such fragile material," says Natalija Kashuba, who was affiliated to The Museum of Cultural History in Oslo when she performed the experiments in cooperation with Stockholm University."It took some work before the results overwhelmed us, as we understood that we stumbled into this almost 'forensic research', sequencing DNA from these mastic lumps, which were spat out at the site some 10,000 years ago!" says Natalija Kashuba. Today Natalija is a Ph.D. student at Uppsala University.The results show that, genetically, the individuals whose DNA was found share close genetic affinity to other hunter-gatherers in Sweden and to early Mesolithic populations from Ice Age Europe. However, the tools produced at the site were a part of lithic technology brought to Scandinavia from the East European Plain, modern day Russia. This scenario of a culture and genetic influx into Scandinavia from two routes was proposed in earlier studies, and these ancient chewing gums provides an exciting link directly between the tools and materials used and human genetics.Emrah Kirdök at Stockholm University conducted the computational analyses of the DNA. "Demography analysis suggests that the genetic composition of Huseby Klev individuals show more similarity to western hunter-gatherer populations than eastern hunter-gatherers," he says."DNA from these ancient chewing gums have an enormous potential not only for tracing the origin and movement of peoples long time ago, but also for providing insights in their social relations, diseases and food.," says Per Persson at the Museum of Cultural History in Oslo. "Much of our history is visible in the DNA we carry with us, so we try to look for DNA where ever we believe we can find it," says Anders Götherström, at the Archaeological Research Laboratory at Stockholm University, where the work was conducted. The study is published in
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Genetically Modified
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May 8, 2019
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https://www.sciencedaily.com/releases/2019/05/190508134554.htm
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Phage therapy treats patient with drug-resistant bacterial infection
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The patient, a 15-year-old girl, had come to London's Great Ormond Street Hospital for a double lung transplant.
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It was the summer of 2017, and her lungs were struggling to reach even a third of their normal function. She had cystic fibrosis, a genetic disease that clogs lungs with mucus and plagues patients with persistent infections. For eight years, she had been taking antibiotics to control two stubborn bacterial strains.Weeks after the transplant, doctors noticed redness at the site of her surgical wound and signs of infection in her liver. Then, they saw nodules -- pockets of bacteria pushing up through the skin -- on her arms, legs, and buttocks. The girl's infection had spread, and traditional antibiotics were no longer working.Now, a new personalized treatment is helping the girl heal. The treatment relies on genetically engineering bacteriophages, viruses that can infect and kill bacteria. Over the next six months, nearly all of the girl's skin nodules disappeared, her surgical wound began closing, and her liver function improved, scientists report May 8, 2019, in the journal The work is the first to demonstrate the safe and effective use of engineered bacteriophages in a human patient, says Graham Hatfull, a Howard Hughes Medical Institute (HHMI) Professor at the University of Pittsburgh. Such a treatment could offer a personalized approach to countering drug-resistant bacteria. It could even potentially be used more broadly for controlling diseases like tuberculosis."The idea is to use bacteriophages as antibiotics -- as something we could use to kill bacteria that cause infection," Hatfull says.In October 2017, Hatfull received the email that set his team on a months-long bacteriophage-finding quest.A colleague at the London hospital laid out the case: two patients, both teenagers. Both had cystic fibrosis and had received double lung transplants to help restore lung function. Both had been chronically infected with strains of The infections had settled in years ago and flared up after the transplant. "These bugs didn't respond to antibiotics," Hatfull says. "They're highly drug-resistant strains of bacteria."But maybe something else could help. Hatfull, a molecular geneticist, had spent over three decades amassing a colossal collection of bacteriophages, or phages, from the environment. Hatfull's colleague asked whether any of these phages could target the patients' strains.It was a fanciful idea, Hatfull says, and he was intrigued. His phage collection ¬- the largest in the world -- resided in roughly 15,000 vials and filled the shelves of two six-foot-tall freezers in his lab. They had been collected from thousands of different locations worldwide -- and largely by students.Hatfull leads an HHMI program called SEA-PHAGES that offers college freshmen and sophomores the opportunity to hunt for phages. In 2018, nearly 120 universities and colleges and 4,500 students nationwide participated in the program, which has involved more than 20,000 students in the past decade.There are more than a nonillion (that's a quadrillion times a quadrillion) phages in the dirt, water, and air. After testing samples to find a phage, students study it. They'll see what it looks like under an electron microscope, sequence its genome, test how well it infects and kills bacteria, and figure out where it fits on the phage family tree."This program engages beginning students in real science," says David Asai, HHMI's senior director for science education and director of the SEA-PHAGES program. "Whatever they discover is new information." That basic biological info is valuable, he says. "Now the phage collection has actually contributed to helping a patient."That wasn't the program's original intent, Asai and Hatfull say. "I had a sense that this collection was enormously powerful for addressing all sorts of questions in biology," Hatfull says. "But we didn't think we'd ever get to a point of using these phages therapeutically."The idea of phage therapy has been around for nearly a century. But until recently, there wasn't much data about the treatment's safety and efficacy. In 2017, doctors in San Diego, California, successfully used phages to treat a patient with a multidrug-resistant bacterium. That case, and the rise of antibiotic resistance, has fueled interest in phages, Hatfull says.Less than a month after he heard about the two infected patients in London, he received samples of their bacterial strains. His team searched their collection for phages that could potentially target the bacteria.They tested individual phages known to infect bacterial relatives of the patients' strains, and mixed thousands of other phages together and tested the lot. They were looking for something that could clear the whitish film of bacteria growing on plastic dishes in the lab. If a phage could do that, the team reasoned, it might able to fight the patients' infections.In late January, the team found a winner -- a phage that could hit the strain that infected one of the teenagers. But they were too late, Hatfull says. The patient had died earlier that month. "These really are severe, life-threating infections," he says.His team had a few leads for the second patient, though: three phages, named Muddy, ZoeJ, and BPs. Muddy could infect and kill the girl's bacteria, but ZoeJ and BPs weren't quite so efficient. So Hatfull and his colleagues tweaked the two phages' genomes to turn them into bacteria killers. They removed a gene that lets the phages reproduce harmlessly within a bacterial cell. Without the gene, the phages reproduce and burst from the cell, destroying it. Then they combined the trio into a phage cocktail, purified it, and tested it for safety.In June 2018, doctors administered the cocktail to the patient via an IV twice daily with a billion phage particles in every dose. After six weeks, a liver scan revealed that the infection had essentially disappeared. Today, only one or two of the girl's skin nodules remain. Hatfull has high hopes: the bacteria haven't shown any signs of developing resistance to the phages, and his team has prepped a fourth phage to add to the mix.Finding the right phages for each patient is a big challenge, Hatfull says. One day, scientists may be able to concoct a phage cocktail that works more broadly to treat diseases, like the Pseudomonas infections that threaten burn patients."We're sort of in uncharted territory," he says. But the basics of the young woman's case are pretty simple, he adds. "We purified the phages, we gave them to the patient, and the patient got better."
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Genetically Modified
| 2,019 |
May 2, 2019
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https://www.sciencedaily.com/releases/2019/05/190502100849.htm
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Mathematician's breakthrough on non-toxic pest control
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A University of Sussex mathematician, Dr Konstantin Blyuss, working with biologists at the National Academy of Sciences of Ukraine, has developed a chemical-free way to precisely target a parasitic worm that destroys wheat crops.
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This breakthrough method of pest control works with the plant's own genes to kill specific microscopic worms, called nematodes, without harming any other insects, birds or mammals.Dr Konstantin Blyuss, from the School of Mathematical and Physical Sciences at the University of Sussex, said:"With a rising global population needing to be fed, and an urgent need to switch from fossil fuels to biofuels, our research is an important step forward in the search for environmentally safe crop protection which doesn't harm bees or other insects."An estimated $130 billion worth of crops are lost every year to diseases caused by nematodes.Targeting the harmful nematodes with chemical pesticides is problematic because they can indiscriminately harm other insects.There are naturally occurring bacteria contained in soil which can help protect plants against harmful nematodes, but until now there has not been an effective way to harness the power of these bacteria to protect crops on a large scale.Dr Blyuss and his colleagues have used 'RNA interference' (RNAi) to precisely target a species of nematode that harms wheat.Dr Blyuss explained:"A nematode, as all other living organisms, requires some proteins to be produced to survive and make offspring, and RNA interference is a process which stops, or silences, production of these."The team has developed a method to 'silence' the harmful nematode's genes by using biostimulants derived from naturally occurring soil bacteria. The biostimulants also 'switch off' the plant's own genes that are affected by the nematodes, making it much harder for the parasite to harm the crop.The gene silencing process is triggered when biostimulants, which are metabolites of bacteria occurring naturally in the soil, are applied to wheat. The biostimulants can be applied either by soaking the seeds or roots in a solution containing the biostimulants, or by adding the solution to the soil in which the plants are growing.Dr Blyuss said:"By soaking the seeds of the plant in the solution of biostimulants, the plant becomes a 'Trojan horse' for delivering special compounds produced inside the plants to the nematodes, which then kills them. We've targeted the specific genes of the nematode, so we know this won't affect other creatures."The biostimulants only affect specific nematode and plant genes, and do not harm other species of insects. And because they are naturally occurring, rather than made of chemicals, they could potentially be used by organic farmers to make organic food more affordable in future.Dr Blyuss' mathematical modelling explains how RNA interference works in plants and shows the most effective way to apply the biostimulants to keep the crop safe from the harmful nematodes.The team's experiments show that soaking the seeds of the plants in the biostimulant solution increases the chances of the plants surviving by between 57 to 92%. The technique also reduces the level of nematode infestation by 73 to 83% compared to plants grown without biostimulants.Explaining the research Dr Blyuss said:"By using mathematical models, we learned how biostimulants are absorbed by wheat plants, so we now know the best way to deliver them. We've also looked at how the RNAi develops inside the plants and nematodes, how the plant is able to switch off specific genes involved in the process of nematode parasitism, thus stopping infestation, and how parts of RNAi from plants, when ingested by nematodes, cause their death by silencing some of their essential genes.These insights were combined with advanced experimental work on developing new strains of soil bacteria and extracting their metabolites, as well as with state-of-the-art molecular genetics analyses, to develop a new generation of environmentally safe tools for control of wheat nematodes."Some people are wary of genetically modified plants, so it's important to be clear that that is not what this is. Biostimulants effectively act as an 'inoculation' against nematode infestation. They achieve their effect by mobilising plants' internal machinery to produce compounds that protect plants against nematodes, while simultaneously causing nematode death.The plants produced using biostimulants have much better crop yields and higher resistance to pests, but they are no different from other plants that have been artificially bred to have some useful characteristic. Moreover, the biostimulants themselves are truly natural, as they are nothing else but products of bacteria already living in the soil. "The breakthrough is published in a paper in the journal Prof Galyna Iutynska, who led the experimental work on development of biostimulants, said:"This work is very exciting because our biostimulants are obtained from products of naturally occurring soil bacteria, which are not genetically modified. The importance of this is that unlike chemical pesticides, these biostimulants can also be used to protect a variety of agricultural crops against parasites in the context of organic farming, which is a particularly challenging problem. Furthermore, these biostimulants can replace chemical pesticides or significantly reduce their use, thus limiting potential negative impact on the environment"The next steps are to develop more advanced mathematical models of how biostimulants with multiple components can be taken up from the soil by both seeds and roots; and to identify which of the most recently identified genetic targets in the nematode are most effective.Professor Dave Goulson from the University of Sussex's School of Life Sciences, and a global expert on declining bee populations, said:"There is growing awareness that the heavy use of conventional pesticides in farming is causing great harm to biodiversity, resulting in pollution of soils and waterways with harmful toxins. We urgently need to find alternative, sustainable means to control crop pests."Dr Blyuss's work was supported by the interdisciplinary Data Intensive Science Centre at the University of Sussex (DISCUS).
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Genetically Modified
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April 26, 2019
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https://www.sciencedaily.com/releases/2019/04/190426110551.htm
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Screening for genes to improve protein production in yeast
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esearchers from The Novo Nordisk Foundation Center for Biosustainability at Technical University of Denmark (DTU), Chalmers University of Technology and KTH Royal Institute of Technology have identified 9 gene targets which upon combinatorial silencing improve protein production in engineered yeast cells by 2.2-fold.
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"The concept can be extended to other yeast protein producers, even some filamentous fungi and mammalian cell factories. Any organization that works with superior protein producers can use these findings," says first-author Postdoc Guokun Wang from The Novo Nordisk Foundation Center for Biosustainability at DTU.The method was used to improve the yeast's production of α-amylase -- a model protein which indicates overall production values of sought-for proteins (recombinant proteins) in the cell.The optimized yeast strain was achieved by determining several gene targets suitable for silencing via RNA interference (RNAi). By building short/long strands of RNA complementary to the gene, the interfering RNA interacts with the complementary mRNA and directs it for degradation, resulting in less mRNA to be translated, hence lowering the expression of the targeted gene.Expression downregulation by RNAi is a powerful tool for efficient rational screening of new genetic targets for beneficial expression tuning since it is cheap and quick.The researchers analyzed approximately 243,000 silencing effectors in yeast by looking at the enhanced secretion of α-amylase as an indicator of improved recombinant protein production.Using extensive screening of tiny droplets containing single cells secreting the enzyme, the researchers managed to pick out nine genes, which upon silencing improved protein secretion. These genes are involved in cellular metabolism, cell cycle as well as protein modification and degradation."All these genes can impact recombinant protein production when expressed at differentially downregulated levels. This knowledge is really important when trying to build optimized yeast cell factories for the production of industrial enzymes or biopharmaceutical proteins," says Guokun Wang.The scientists first screened beneficial RNAi targets. Afterwards, they looked at combinations of silencing, leading to a so-called semi-rational approach. The research has now been published in
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Genetically Modified
| 2,019 |
April 23, 2019
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https://www.sciencedaily.com/releases/2019/04/190423133727.htm
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Welding with stem cells for next-generation surgical glues
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Scientists at the University of Bristol have invented a new technology that could lead to the development of a new generation of smart surgical glues and dressings for chronic wounds. The new method, pioneered by Dr Adam Perriman and colleagues, involves re-engineering the membranes of stem cells to effectively "weld" the cells together.
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Cell membrane re-engineering is emerging as a powerful tool for the development of next generation cell therapies, as it allows scientists to provide additional functions in the therapeutic cells, such as homing, adhesion or hypoxia (low oxygen) resistance. At the moment, there are few examples where the cell membrane is re-engineered to display active enzymes that drive extracellular matrix production, which is an essential process in wound healing.In this research, published in Dr Adam Perriman, Associate Professor in Biomaterials in the School of Cellular and Molecular Medicine, said: "One of the biggest challenges in cell therapies is the need to protect the cells from aggressive environments after transplantation. We have developed a completely new technology that allows cells to grow their own artificial extracellular matrix, enabling cells to protect themselves and allowing them to thrive after transplantation."The team's findings could increase the possibilities in tissue engineering for chronic wound healing, especially because the process uses fibrinogen, which is abundant in blood.The researcher's new method of the conversion of natural enzymes into a membrane binding proteins, could pave the way for the development of a wide range of new biotechnologies.
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Genetically Modified
| 2,019 |
April 23, 2019
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https://www.sciencedaily.com/releases/2019/04/190423133557.htm
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Bacteria reveal strong individuality when navigating a maze
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Although they are considered the simplest of all life forms, even microorganisms sense their environment and are able to actively move within it. This allows them to identify both food and harmful substances and to move towards or away from them, guided by the concentration gradient of the substance in their environment. The journey of many microbes can thus be viewed as a sequence of decisions based on chemical gradients.
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The ability of cells to target or avoid particular substances is called chemotaxis. Until now, scientists have generally considered the chemotactic properties of bacteria to be a common feature of a species or population -- as if all cells behaved more or less the same. In this case, average values are sufficient to describe their movement behaviour. Now, researchers at ETH Zurich have observed the chemotaxis of bacteria in a behavioural experiment. "If you look with the appropriate technology, you'll find astonishing behavioural differences even within a population of genetically identical cells," report Mehdi Salek and Francesco Carrara, the lead authors of a study recently published in Together with their colleagues in the research group led by Professor Roman Stocker at the Institute of Environmental Engineering, they have developed a special microfluidic system that allows them to observe the movement of thousands of individual bacteria in a liquid at extremely small scales. The system comprises a series of narrow channels that branch out on to a thin glass plate to form a sort of microscopic maze through which the bacteria swim.Such mazes are often used in experimental studies of the behavioural preferences of other organisms, such as insects or worms (and also plant roots). With their microfluidic system, the ETH researchers were able for the first time to apply this traditional tool of ecologists on a microscopic scale. Their maze resembles a family tree, with a starting channel that branches out again and again towards the bottom, where the concentration of a chemical attractant is at its highest.The bacteria all start in the same place -- and visibly divide up within the channel system as they are forced to decide at each fork whether to swim up or down the gradient of attractant. The bacteria owe their chemotactic abilities to specialised receptors that allow them to identify the attractant. In addition, they have about half a dozen flagella, which can rotate either clockwise or anti-clockwise. "Based on this, the bacterium changes its direction or continues to swim in one direction," explain Salek and Carrara.Even within a group of genetically identical cells -- that is, clones -- the ETH researchers found individuals that were able to follow the attractant well (by navigating towards the higher concentration whenever they came to a fork), and those that were less able to negotiate the maze. The scientists attribute these behavioural differences to variations in the genetic activity of identical genes in sister cells. This means the cells have different amounts of the corresponding proteins. "There is biochemical noise in every cell. As a fundamental random component, this causes diversity of appearance and behaviour," say the researchers.Diversity, or heterogeneity, of chemotaxis may provide an evolutionary advantage for the bacteria, since although those skilled at chemotaxis can quickly locate and exploit locally stable food sources, their sister cells less affected by the attractant are more likely to venture into new territory, where they may encounter additional food sources in a constantly changing environment."Non-genetic diversity has long been known in the biomedical life sciences; for example, it is thought to play a role in antibiotic resistance. Now, environmental scientists have shown that this diversity also affects fundamental behaviours of bacteria, such as locomotion and chemotaxis -- further expanding the concept of bacterial individuality," says Stocker. He assumes that the varying individual behaviour of bacteria may also be relevant to gaining a better understanding of processes such as the pathogenic infection of corals or the bioremediation of oil spills.
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Genetically Modified
| 2,019 |
April 15, 2019
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https://www.sciencedaily.com/releases/2019/04/190415154659.htm
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Pollen genes mutate naturally in only some strains of corn
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Pollen genes mutate naturally in only some strains of corn, according to Rutgers-led research that helps explain the genetic instability in certain strains and may lead to better breeding of corn and other crops.
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Scientists at Rutgers University-New Brunswick and Montclair State University looked at gene mutations that arise spontaneously in corn plant pollen. Pollen grains are the male gametes, or reproductive cells, in corn plants. The scientists estimated there were several mutations per gene per million pollen grains, according to their study in the journal Since a typical corn plant produces about 10 million pollen grains, a single plant in some lines, or strains, of the vital crop will produce mutations in every gene in its genome in one season. In other lines, mutations were not detected in either sex, said lead author Hugo K. Dooner, Distinguished Professor Emeritus at the Waksman Institute of Microbiology.The United States is the world's largest corn producer, with about 409 million tons grown on about 90 million acres in fiscal 2017-18, according to the U.S. Department of Agriculture. Feed grain consists of more than 95 percent of the production and use of corn in the United States. Corn also is processed into a wide range of food and industrial products, including cereal, alcohol, sweeteners and byproduct feeds.In all organisms, mutations that happen spontaneously provide the raw material for natural selection and evolution. But mutations are so infrequent that scientists use special "mutation accumulation" lines to study them. The Rutgers-led team found that the mutations in pollen were caused primarily by mobile retrotransposons, which are like retroviruses in mammals, within the corn plant. Retroviruses invade cells, convert their viral RNA to DNA and merge it with the cells' DNA."We found that spontaneous mutations in corn genes arise relatively frequently in the pollen of some but not all lines," Dooner said.Next steps are to investigate whether retrotransposon-induced mutations cause the genetic instability in corn lines previously reported by breeders, and whether activating retrotransposons in corn and other important crops could benefit them.
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Genetically Modified
| 2,019 |
April 15, 2019
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https://www.sciencedaily.com/releases/2019/04/190415113810.htm
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Engineering 'hairpins' increases CRISPR accuracy
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Biomedical engineers at Duke University have developed a method for improving the accuracy of the CRISPR genome editing technology by an average of 50-fold. They believe it can be easily translated to any of the editing technology's continually expanding formats.
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The approach adds a short tail to the guide RNA which is used to identify a sequence of DNA for editing. This added tail folds back and binds onto itself, creating a "lock" that can only be undone by the targeted DNA sequence.The study appears online on April 15 in the journal "CRISPR is generally incredibly accurate, but there are examples that have shown off-target activity, so there's been broad interest across the field in increasing specificity," said Charles Gersbach, the Rooney Family Associate Professor of Biomedical Engineering at Duke. "But the solutions proposed thus far cannot be easily translated between different CRISPR systems."CRISPR/Cas9 is a defense system that bacteria use to target and cleave the DNA of invading viruses. While the first version of CRISPR technology engineered to work in human cells originated from a bacteria called Streptococcus pyogenes, many more bacteria species carry other versions.Scientists in the field have spent years looking for new CRISPR systems with desirable properties and are constantly adding to the CRISPR arsenal. For example, some systems are smaller and better able to fit inside of a viral vector to deliver to human cells for gene therapy. But no matter their individual abilities, all have produced unwanted genetic edits at times.A universal property of CRISPR systems is their use of RNA molecules as guides that home in on the targeted DNA sequence in the genome. Once a guide RNA finds its complementary genetic sequence, the Cas9 enzyme acts as the scissors that make the cut in the DNA, facilitating changes to the genome sequence. But because each homing sequence is only 20 nucleotides long and the human genome contains about three billion base pairs, there's a lot to sort through, and the CRISPR can sometimes make mistakes with sequences one or two base pairs short of perfection.One way to improve CRISPR's accuracy is to require two Cas9 molecules to bind onto opposite sides of the same DNA sequence for a complete cut to be made. While this approach works, it adds more parts to the system, increasing its complexity and making it harder to deliver.Another approach has been to genetically engineer the Cas9 protein to make it less energetic, so it's less likely to jump the gun and make a mistake. While this has also shown promising results, this type of protein engineering is laborious and such efforts are specific to each CRISPR system."It seems like there's a new CRISPR system being discovered almost every week that has some kind of unique property that makes it useful for a specific application," said Gersbach. "Doing extensive re-engineering every time we find a new CRISPR protein to make it more accurate is not a straightforward solution.""We're focused on a solution that doesn't add more parts and is general to any kind of CRISPR system," said Dewran Kocak, the PhD student working in Gersbach's laboratory who led this project. "What's common to all CRISPR systems is the guide RNA, and these short RNAs are much easier to engineer."Gersbach and Kocak's solution is to extend the guide RNA by as many as 20 nucleotides in such a way that it folds back onto itself and binds onto the end of the original guide RNA, forming a hairpin shape. This creates a sort of lock that is very difficult to displace if even a single base pair is incorrect in a DNA sequence being scrutinized for a potential cut. But because the guide RNA would prefer to bind to DNA rather than itself, the correct combination of DNA is still able to break the lock."We're able to fine-tune the strength of the lock just enough so that the guide RNA still works when it meets its correct match," said Kocak.In the paper, Kocak and Gersbach show that this method can increase the accuracy of cuts being made in human cells by an average of 50-fold across five different CRISPR systems derived from four different bacterial strains. And in one case that improvement rose to over 200 fold."It's a pretty simple idea even though Dewran completed several years' worth of research to show that it works the way that we think it's working," said Gersbach. "It's a nice, elegant solution for getting rid of off-target activity."Moving forward, the researchers hope to see just how many different CRISPR variants this approach could work with as well as complete an in-depth characterization of exactly how the locking mechanism works to see if there are differences across CRISPR variants. And because these experiments were conducted in cultured cells, the researchers are eager to see how well this approach might increase CRISPR accuracy within an actual animal model of disease.
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Genetically Modified
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April 8, 2019
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https://www.sciencedaily.com/releases/2019/04/190408114310.htm
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These molecules could trap viruses inside a cell
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Viruses are often used as vehicles for delivery in gene therapy because they're engineered not to damage the cell once they get there, but neglecting to consider how the virus will exit the cell could have consequences.
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Some viruses use a molecule called heparan sulfate to help them attach to cells. The molecule, found in many different kinds of cells (including those from animal tissue), could prevent the virus from escaping, according to a new study in the journal "It isn't necessarily a good thing that the virus isn't being released. That could have its own consequences on stimulating the immune system," said David Sanders, an associate professor of biological sciences at Purdue University. "As we're engineering viruses more and more to do gene transfer and gene therapy, one thing we need to be taking into account is their ability to exit the cell."Gene therapy is a relatively new technique that uses genes, rather than drugs or surgery, to treat a disorder. It can be done a few ways: by replacing a disease-causing gene with a healthy copy of the gene, knocking out a mutated gene that doesn't function correctly, or introducing an entirely new gene that would help the body fight disease.Viruses used in gene delivery are engineered not to cause disease in a new host, but whether there will be unintended consequences of a virus never leaving the cell remains an unanswered question."Heparan sulfate is potentially useful because rather than having the protein search for the cell's receptor in three-dimensional space, it brings the protein to the surface. Once there, it makes the search two-dimensional," Sanders said. "But when we introduced our virus into a cell that makes heparan sulfate, it wasn't able to escape."Retroviruses, such as HIV, insert a copy of their genome into the DNAell they invade. Because retroviruses are permanently incorporated into the host cell's genetic material, they work well as vehicles for gene transfer.To see if they could generate a virus that enhances the insertion of DNA into cells that have heparan sulfate on their surfaces, Sanders' team created a viral pseudotype: a retrovirus that looks like an alphavirus from the outside. Then they made changes to the alphavirus protein that were predicted to make the pseudotyped virus utilize heparan sulfate for entry."Rather than creating a better virus, we found practically no virus," Sanders said. "Because of the interaction between the protein we modified and the heparan sulfate already in the cell, the protein was being retained there."When viruses are incubated with cells in petri dishes, they sometimes acquire the ability to use heparan sulfate. This phenomenon has been observed in several types of viruses, and although they wouldn't use heparan sulfate in a standard living organism, something about cell culture makes them more likely to utilize the molecule.As viruses are increasingly being designed as delivery vehicles, researchers should consider that the tools they use to facilitate entry could interfere with exit, Sanders said.
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Genetically Modified
| 2,019 |
April 4, 2019
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https://www.sciencedaily.com/releases/2019/04/190404143710.htm
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Scientists genetically engineer yeast to improve understanding of how cells work
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Researchers have 'fine-tuned' a major cell signalling mechanism by rewriting DNA inside yeast cells to control how they respond to their environment.
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The study, which was published today by Academics from the University of Cambridge and Imperial College London, in collaboration with AstraZeneca, used mathematical modelling and genome engineering to edit yeast cells to help scientists control not just what the cells sense but how they react to what they sense in a more desirable way.Yeast was chosen because it shares key characteristics with human cells -- most importantly that it can sense its environment using G protein-coupled receptors (GPCRs).Dr Graham Ladds, a lecturer in the Department of Pharmacology and a Fellow of St John's College, University of Cambridge, said: "Yeast was used as a mechanism to understand what happens in humans. We used mathematical modelling and genetic modification to edit the cell and retune what its response should be."GPCRs are receptors which enable cells to sense chemical substances such as hormones, poisons, and drugs in their environment. The cells read their environment and sense the levels of hormones such as adrenalin, serotonin, histamine and dopamine. They can also act as light, smell and flavour receptors with some located on the tongue to give us our sense of taste.There are around 800 different GPCRs in our bodies and around half of all medication acts using these receptors -- including beta blockers, antihistamines and various kinds of psychiatric drugs. But not enough is known about how GPCR signalling works.One of the difficulties for researchers is that DNA variations can have an impact on the signalling network and determining how parts of the DNA affect this is a major challenge.The Cambridge team created a mathematical model of the yeast cell with varied concentrations of different cell components and found the optimum levels for the most efficient signalling of each one. This knowledge was then used to genetically modify cells by a team of researchers at Imperial College London.Dr William Shaw, first author on the paper and researcher at the Bioengineering department of Imperial College London, explained: "It enabled us to understand exactly how we can genetically engineer a cell so it senses the desired amount of something for us in a way that we have control of."Guided by the computational findings, we created a highly-modified strain of yeast with all the non-essential interactions within the GPCR signalling pathway removed. By varying the levels key components identified in the model we were able to predictably alter the way the cells responded to their environment."Dr Tom Ellis, from the Bioengineering Department at Imperial College London and the paper's senior author, added: "We learned important principles about why cells will respond differently to the same molecules of the same concentrations. If there's a variation in the DNA sequence that determines key component levels, then this can change everything."Dr Mark Wigglesworth, Director of Hit Discovery at AstraZeneca, said: "GPCRs are fundamentally important to the function of healthy cell systems and they remain one of the most targeted proteins in human medicine. It is hoped that increasing our understanding of these proteins will lead to more innovative medicines in the future."
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Genetically Modified
| 2,019 |
April 4, 2019
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https://www.sciencedaily.com/releases/2019/04/190404094909.htm
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Researchers engineer a cost-effective treatment for neglected tropical disease
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Researchers have turned a fungus into a disease-curing factory through modern genetic engineering and patience. The natural antibiotic is a promising cure for a neglected tropical disease called human African trypanosomiasis, or African sleeping sickness, that infects thousands of people in remote, rural areas of sub-Saharan Africa each year.
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"Our collaboration started about four years ago, and we have finally achieved our goal," said Professor Ikuro Abe from the University of Tokyo Department of Pharmaceutical Sciences."The gene cluster in the fungus is unique -- through a simple genetic deletion, we have engineered a strain of the fungus that only produces high concentrations of the desired antibiotic," explained Abe.Professor Kiyoshi Kita, who retired from the University of Tokyo in 2016, dedicated a large portion of his career to understanding and curing African sleeping sickness. Abe's research team joined the project due to their expertise in mapping the chemical paths that lead from genes to proteins inside cells.Abe's research team used their biosynthesis pathway expertise to genetically modify the fungus so that it produces large quantities of one specific antibiotic.The fungus Artificially synthesizing the antibiotic would not be cost effective and the more common method of using bacteria to produce the chemical is infeasible.Abe's research team identified that the fungus's two antibiotics are both made from the same precursor molecule. After the precursor is created, two separate groups of enzymes produce the two different antibiotics.Researchers can leave the precursor molecule and the genes responsible for the desired antibiotic completely unchanged by simply deleting the genes responsible for the other toxic antibiotic.In every liter of fungus that researchers grow in the lab, the engineered strain of the fungus can produce 500 milligrams of antibiotic."We think this is an exceptionally good production system," said Abe.Researchers have applied for a patent on the engineered strain of fungus. Collaborators at the Kikkoman Corporation, best known for making soy sauce, will pursue industrial-scale growth of the genetically engineered fungus and purification of the antibiotic.The desired antibiotic, ascofuranone, is also a candidate treatment for cancer.People can develop African sleeping sickness by being bitten by a fly. The disease is caused by a parasite that moves from the flies, to patients' blood streams, and then into the nerves of patients' brains and spinal cords. The disease is often fatal within three years. The same parasite can also infect livestock animals.The World Health Organization aims to eliminate human African trypanosomiasis as a public health problem by 2020.
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Genetically Modified
| 2,019 |
April 2, 2019
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https://www.sciencedaily.com/releases/2019/04/190402124352.htm
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Nature versus nurture: Environment exerts greater influence on corn health than genetics
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Corn is one of the most important staple crops in the world -- over 1 billion metric tons of corn are harvested each year, comprising 37 percent of the global cereal production. Corn production occupies an estimated 188 million hectares -- roughly the size of Mexico -- and utilizes 13 percent of the world's arable land. Because of this, there is a vested interest in keeping corn healthy.
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Corn leaves are teaming with bacteria communities (the leaf "microbiome") that influence plant health and performance, and scientists are still figuring out how. A team of scientists led by Dr. Jason Wallace recently published a study in the open access In one of the largest and most diverse leaf microbe studies to date, the team monitored the active bacteria on the leaves of 300 diverse lines of corn growing in a common environment. They were especially interested to see how corn genes affected bacteria and found there was little relationship between the two -- in fact, the bacteria were much more affected by the environment, although genetics still had a small role.This is an interesting discovery that "breeding probably isn't the best way to address this," Dr. Wallace says. Instead, "the leaf community is probably better changed through farmer management." That is, farmers should be able to change growing practices to enhance their current crops rather than seek out new plant varieties.Going forward, Dr. Wallace suggests research into the functions of these bacterial communities, and then combining this knowledge to full systems-level understanding of the leaf community may enable development of beneficial management practices for farmers.
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Genetically Modified
| 2,019 |
April 2, 2019
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https://www.sciencedaily.com/releases/2019/04/190402113013.htm
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Fast-changing genetics key to hospital superbug survival
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For the study, published today in
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By genetically analysing 100 strains of The hospital outbreak strains of With the number of deaths from drug-resistant infections predicted to rise from 700,000 to 10 million per year by 2050, Carbapenem-resistant Enterobacteriaceae are listed as one of three urgent threats by the Centers for Disease Control and Prevention and a key global 'critical-priority' by the World Health Organization."Bacteria common in hospitals world-wide have an increasing number of genomic tools in their arsenal to spread and cause deadly infections. Carbapenems are the drugs we use when nothing else works, so an increase in bacteria with resistance to Carbapenems is a really significant public health threat. It means we're out of treatment options and need to increase our global study and surveillance of these bacteria," explained study author Professor Francois Balloux (UCL Genetics Institute).The team used whole genome DNA sequence data to reconstruct the evolution of the highly drug-resistant bacteria, including tracking their transmission within the hospital, spanning three campuses, 19 wards and two intensive care units."Using genome-wide genetic data we could clearly follow their spread around the hospital. It's remarkable to see how easily these bacteria were moving between patients, particularly those in intensive care units, but we also found that they were transmitting across different hospital sites via ward equipment, including ward bed rails and medical devices," said Dr Lucy van Dorp (UCL Genetics Institute), first author and lead researcher on the British team."We found that these bacteria had been in circulation in the hospital for at least a year before we began our surveillance initiative, suggesting the index patient was probably not involved in any subsequent transmission to other patients. Reassuringly, the As well as tracing the spread of the outbreak, the researchers also considered which parts of the bacterial genome were carrying the genes that are needed to evade antibiotic therapy."Bacteria like Klebsiella carry additional DNA packaged up into mobile transferable elements called plasmids," explained Professor Balloux. "The bacteria from this outbreak had extraordinary diversity in the plasmids they carried, and it was these units that held the genes which were helping the bacteria to continue to infect patients, even in the face of treatment with Carbapenems."Plasmids allow bacteria to easily transfer genetic information between organisms and are present in many of the species of bacteria that are both common in hospitals and are responsible for infections that are becoming increasingly hard to treat, globally.In this study, genomic data revealed that most of the outbreak isolates of "We found the bacteria were carrying many resistance plasmids, and in some cases these plasmids were present in multiple copies. We demonstrated that the number of copies helped to predict how successfully treatment was evaded by the bacteria. This means it isn't just the presence of a gene conferring resistance that is important, but also its abundance in an infecting strain," explained Dr van Dorp."Most DNA sequencing-based diagnostics used to track outbreaks currently don't consider this fact, which shows how valuable genome sequencing is as a tool for investigating multi-drug-resistant hospital outbreaks."The research was made possible by the participation of patients and staff at Peking University People's Hospital. The study was funded by the Newton Trust UK-China NSFC initiative.
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Genetically Modified
| 2,019 |
March 29, 2019
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https://www.sciencedaily.com/releases/2019/03/190329130235.htm
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New plant breeding technologies for food security
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An international team, including researchers from the University of Göttingen, argues in a perspective article recently published in
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"Plant breeding and other agricultural technologies have contributed considerably to hunger reduction during the last few decades," says Matin Qaim, an agricultural economist at the University of Göttingen and one of the article's authors. But the resulting high intensity in the use of agrochemicals has also caused serious environmental problems. Future technologies need to reduce the negative environmental footprint and make agriculture more resilient to climate stress. Predictions suggest that small farms in Africa and Asia will suffer especially from the effects of climate change."Genome editing allows us to develop crop plants that are more resistant to pests and diseases and more tolerant to drought and heat," says Shahid Mansoor from the National Institute for Biotechnology and Genetic Engineering in Pakistan. This can help to reduce crop losses and chemical pesticide sprays. In genome editing, certain DNA sequences are changed or "switched off" in a very precise way without foreign genes being introduced. Hence, genome-edited crops are different from transgenic genetically modified organisms (GMOs). "The new methods are already being used in various cereals and also to improve neglected food crops such as pulses or local vegetables," Mansoor explains."We should be careful not to repeat the mistakes that were made with GMOs," says Qaim. "The limited public acceptance and the high regulatory hurdles for transgenic GMOs have contributed to a concentration of biotech developments in only a few major crops and in the hands of only a few multinationals. We need more diversity and more competition," adds Qaim. "Genome-edited crops do not contain foreign genes; as the breeding techniques are more precise, these crops are as safe as conventionally bred crops. Hence, genome-edited crops should not be regulated as if they were transgenic GMOs."In Europe, regulations for genome-edited crops are still being debated. In July 2018, the EU Court of Justice ruled that these crops would fall under the existing GMO law, which is disappointing according to the authors of this position paper. "This will hold up future applications" says Qaim. The regulation of new breeding technologies in Europe also has a major impact on developing countries, carrying the risk that the enormous potential of genome editing for food security cannot be fully harnessed, the researchers fear.
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Genetically Modified
| 2,019 |
March 22, 2019
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https://www.sciencedaily.com/releases/2019/03/190322105725.htm
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A social bacterium with versatile habits
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Many living systems share a fundamental capacity for cooperation. Plants and animals are made up of billions of cells that communicate with one another, carry out specific tasks and share their resources. Many single-celled microorganisms cooperate in similarly versatile ways: they form communities and exchange useful genes and resources among one other.
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The microbe Researchers previously had theoretical reasons to expect that cooperative groups of microbes in nature might generally be socially homogeneous, as this would prevent conflict between cells from undermining cooperation. Genetically distinct individuals from different groups have been shown to often avoid, obstruct, and even combat each other. "Our knowledge about the genetic composition within cooperative groups of these social bacteria in nature used to be very limited," says Sébastien Wielgoss, a lecturer in the research group of Professor Gregory Velicer, Institute for Integrative Biology, ETH Zurich.With their colleagues, Wielgoss and Velicer have more closely examined the genetic relationships between members of the same In a study recently published in For their study, the researchers investigated groups of cells that descended recently from a common ancestor. Mutation formed various socially different, but closely related, cell lines within these groups, with lines differing in how fast they swarm or how many spores they produce within a fruiting body.Some forms of diversity pose a threat to group productivity. For example, individual bacteria can exhibit "cheating" behaviour: they contribute little to the group while exploiting its other members and lowering group function. "However, behavioural studies with these same groups have not found such socially disruptive cheating," Wielgoss said. In contrast, while the majority of groups are highly genetically and socially diverse, the observed diversity does not appear to undermine cooperative functions at the group level.The researchers attribute this high diversity of behavioural patterns to evolutionary selection that focuses on a small number of "social" genes that control the social habits of the bacteria. Mutations in these "selection hotspots" favoured by natural selection cause a variety of behavioural changes, yielding a diverse society of cells with varying levels of spore production and swarming speed. The researchers speculate that distinct lines in the same group likely also differ in their cooperative hunting abilities, although this was not tested in this study.Wielgoss explained that natural selection may favour some combinations of diversified cell lines over other combinations or even over homogeneous groups: "Cell groups with a large behavioural repertoire may respond to environmental changes more effectively. They may often be more evolutionarily successful than homogeneous groups of cells that all behave in the same way. 'Cultural diversity' appears to be rather frequent among bacterial social groups."Microorganisms are omnipresent. They fulfil important functions in our everyday lives: as helpers in our intestinal flora, as pathogens or as agents in food production. Many combine into cooperative groups of cells in nature, too. The researchers believe that these new insights into the genetic and behavioural properties of cooperative soil bacteria may help us to understand cooperation within other types of bacteria as well, including the important pathogen Pseudomonas aeruginosa that infects immuno-compromised patients and causes serious long-term infections.
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Genetically Modified
| 2,019 |
March 21, 2019
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https://www.sciencedaily.com/releases/2019/03/190321152841.htm
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Natural plant defense genes provide clues to safener protection in grain sorghum
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Weeds often emerge at the same time as vulnerable crop seedlings and sneak between plants as crops grow. How do farmers kill them without harming the crops themselves?
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Seed and chemical companies have developed two major technologies to avoid crop injury from soil- and foliar-applied herbicides: genetically modified herbicide-tolerant crops; and safeners, chemicals that selectively -- and mysteriously -- protect certain crops from damage. In a new University of Illinois study, researchers identify genes and metabolic pathways responsible for safener efficacy in grain sorghum.The discovery goes a long way in explaining how safeners work. According to Dean Riechers, weed scientist in the Department of Crop Sciences at U of I and co-author on the Today, after nearly 50 years of commercial use in corn, rice, wheat, and grain sorghum, safeners remain a mystery. The existence of synthetic chemicals that selectively protect high-value cereal crops and not broadleaf crops or weeds is fascinating but doesn't make intuitive sense, according to Riechers. Figuring out how the protective mechanism switches on in cereal crops could one day help scientists induce protection in broadleaf crops, like soybeans and cotton."Finding a safener that works in dicot crops would be the Holy Grail," Riechers says.The first step, however, is understanding what happens inside cells of cereal crops when exposed to safeners. In previous trials with grain sorghum, the research team noticed a massive increase in production of glutathione S-transferases (GSTs). These important enzymes, present in all living organisms, quickly detoxify herbicides and other foreign chemicals before they can cause damage. But that didn't narrow the haystack very much."These cereal crops have up to 100 GSTs, and we didn't know if one or more was providing the protective effect," Riechers says. "We also couldn't tell why GSTs were increased."The team used an approach known as a genome-wide association study. They grew 761 grain sorghum inbred lines in a greenhouse and compared plants treated with safener only, herbicide only, or both safener and herbicide. Scouring the genome for differences, they found specific genes and gene regions that were switched on in the safener-treated plants. Not surprisingly, they were genes that coded for two GSTs."Although we suspected GSTs were involved, this technique seemingly pinpointed the gene responsible for safening sorghum, In addition to finding this key gene for detoxification, the researchers also analyzed the RNA molecules expressed in safener-treated plants and revealed a plant defense pathway pulling double duty.According to Riechers and co-author Patrick Brown, sorghum is well-known for producing allelochemicals, or chemical defenses, against insects and pathogens. One of these, dhurrin, is a chemical with a cyanide group. When it is under attack, sorghum releases a "cyanide bomb," killing the insect or pathogen. It turns out some genes involved in dhurrin synthesis and metabolism were triggered in response to safeners, too."This link to dhurrin was kind of a clue -- maybe the safener is tapping into a chemical defense pathway the plant is already using to protect itself," Riechers says. "This is a new concept no one has ever proposed before in sorghum. It's giving us some insight why the safener might be eliciting this response in the plant."The ability to turn on defenses and protective pathways with safeners could have all sorts of applications, according to Riechers. "It doesn't seem logical there would be a pathway that's only specific for synthetic herbicides," he says. "Maybe safeners could be deployed to protect crops against insect herbivores, chemical pollutants, or environmental stresses. The possibilities and applications are very promising."The researchers have plans and funding to expand the experiment to wheat, and ultimately hope to identify more precise safener-herbicide-crop combinations that could eventually translate to broadleaf crops.
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Genetically Modified
| 2,019 |
March 19, 2019
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https://www.sciencedaily.com/releases/2019/03/190319121721.htm
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Go for a run or eat chocolate: A choice dictated by the cannabinoid receptors
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Physical inactivity is a common factor in lifestyle diseases -- and one that is often linked to the excessive consumption of fatty and/or sugary foods. The opposite scenario of excessive physical activity at the expense of caloric intake can also be harmful, as cases of anorexia nervosa illustrate. These data therefore point to the crucial need to research the neurobiological processes that control the respective motivations for exercise and food intake. A study by Inserm and CNRS researchers published on March 7, 2019 in
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The authors of this paper had previously reported that the cannabinoid type-1 (CB1) receptors, present on several types of neurons, play a key role in performance during physical activity in mice. A conclusion based on the performances achieved by animals with free access to an exercise wheel -- a model in which it was not possible to distinguish the mechanism involved (motivation, pleasure...). Given that the motivation for a reward can only be estimated by measuring the efforts that the individual -- whether human or animal -- is prepared to make to get that reward, the researchers devised a model in which each access to the wheel was conditional on a prior effort. This involved the animal repeatedly introducing its snout into a recipient, an essential prerequisite for unlocking the wheel. After a training period during which the level of effort required to unlock the wheel remained the same, the mice were confronted with a test in which the effort required was gradually increased. When exposed to this test, the mice lacking CB1 receptors showed an 80 % deficit in the maximum effort they were prepared to make to unlock the wheel, and without a decrease in performance during their access to it. This finding indicates that the CB1 receptors play a major role in controlling motivation for exercise. The use of other genetically-modified mice also enabled the researchers to demonstrate that these CB1 receptors controlling motivation for exercise are located on GABAergic neurons.The researchers then examined whether the CB1 receptors in the GABAergic neurons control the motivation for another reward: chocolatey food (like humans, mice love it even when they are otherwise well-fed). While the CB1 receptors also play a role in motivation for food -- albeit to a lesser extent than in motivation for exercise -- the CB1 receptors located on the GABAergic neurons are not implicated in the motivation for eating chocolatey food.In our daily life, we are faced with an ongoing choice between various rewards. A fact which has encouraged the researchers to develop a model in which following a learning period the mice had the choice -- in return for the efforts described above -- between exercise and chocolatey food. The motivation for exercise was greater than that for chocolatey food, with the exception of the mice lacking CB1 -- whether generally or just on GABAergic neurons -- whose preference was for the food.In addition to these findings indicating that the cannabinoid receptor is essential for the motivation for exercise, this study opens up avenues for researching the neurobiological mechanisms behind pathological increases in this motivation. One illustration is provided by anorexia nervosa which often combines the decreased motivation to eat with an increased motivation to exercise.
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Genetically Modified
| 2,019 |
March 4, 2019
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https://www.sciencedaily.com/releases/2019/03/190304121503.htm
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Checking DNA base editor's mistakes and tricks to reduce them
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Researchers at the Center for Genome Engineering, within the Institute for Basic Science (IBS, South Korea) have identified the mistake-rate of DNA editing tools, based on CRISPR and known as adenine base editors. Assessing the genome-wide target specificity of these innovative techniques is essential to harness their applications in clinics and biotechnology. Their findings were published in
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DNA's four letters, or bases, are the alphabet used by our cells: adenines (A) pairs with thymines (T), cytosines (C) with guanines (G), making a unique combination of 3.2 billion letters, that makes us who we are. Since some genetic diseases are caused by a mutation of just one letter, some of the applications of CRISPR -- a very successful and powerful gene engineering tool -- deal with the correction of this single-letter difference. Examples of proteins that can be added to the CRISPR system to promote letter conversions are: cytosine base editors (CBEs) for C-to-T conversions, and adenine base editors (ABEs) for A-to-G changes. The IBS team has been interested in studying ABEs' specificity, as it has not been known so far.The team, led by Jin-Soo Kim, studied the error-rate of recently developed ABE proteins, ABE7.10, in human cells. They pinpointed the positions on the human genome affected by ABE7.10 and scanned for errors beyond the target. To do that, they used an adapted version of Digenome-seq, a sequencing technique developed by the same Research Center, that had already successfully determined the accuracy of CBE, CRISPR/Cas9 and CRISPR/Cpf1, among others. They tested ABE7.10 with seven guide RNAs, corresponding to seven DNA target letters, and also compared the results with a common CBE, and a Cas9 nuclease. The modified Digenome-seq could detect an average of 60 off-target mistakes in the entire human genome. And interestingly, although the three proteins were engineered to target the same site, they recognized different off-target points.IBS biologists also showed some strategies to curb the number of off-target modifications. Adding a couple of Gs at the end of the guide RNA reduced the off-target mistakes, as well as the use of a different type of Cas9 (Sniper-Cas9, developed by the same team in 2018) and the delivery of ABE7.10 via preassembled ribonucleoproteins, rather than via plasmids.The team aims to contribute to the development of ABEs, to introduce the desired single-letter changes in a more precise and efficient way. "As the accuracy of the base editor is proven, we expect that it will find wide application in the future in medical and agricultural realms," says Jin-Soo Kim.
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Genetically Modified
| 2,019 |
February 25, 2019
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https://www.sciencedaily.com/releases/2019/02/190225100726.htm
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GM seed use has exploded in India: Socially motivated decisions
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Suicide rates among Indian farmers remain high, accounting for more than 12,500 deaths in the country in 2015, according to a government report. While many have blamed climate change for farmers' distress, the issue is likely much more complex.
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After the Indian government liberalized the economy in the 1990s, the agricultural sector went through a plethora of changes; national attention shifted from rural to urban landscapes, new development programs exacerbated inequality, and the government pulled back subsidies on fertilizers, pesticides, water and seeds. Shops stocking a previously controlled market of public agricultural goods were suddenly flooded with new private brands."Consumer scientists call this 'choice overload.' When you step into a supermarket and there are 70 types of mustard to buy, it becomes a stressful situation and people no longer want to deal with making that decision," said Andrew Flachs, an environmental anthropologist at Purdue University. "When genetically modified seeds were first introduced, there were just three seeds. Now there are more than 1,200 and figuring out which particular seed to buy has become an incredibly difficult and confusing decision."India is the world's second largest producer of cotton. The crop, which plays a dominant role in the country's industrial and agricultural economies, is extremely pesticide intensive. When genetically modified seeds were being debated in the 1990s, Indian cotton accounted for nearly half of the pesticides sprayed in the country, despite being planted on only five percent of the farmland. Genetically modified cottonseeds are now widely available, (which should, in theory, reduce pesticide use), but national yields have largely stagnated and use of pesticide sprays has increased over the last decade.Telangana, a state in southern India, is a major cotton producer where most seeds are sown by small farmers. It's also where the peak of farmer suicides in the 1990s happened, which is one reason many thought introducing genetically modified seeds would be a good idea.To figure out how farmers here decide which seeds to plant, Flachs conducted surveys while living in Indian villages from 2012 to 2018. He talked to members of farming households about their experience with genetically modified cottonseeds and asked how they rationalized their purchasing choices in a seed market that's nearly bursting at the seams. The findings were published in the journal Flachs argues that without help and expertise from government agencies, cotton farmers in Telangana rely on scripts: socially learned mental maps that reflect local rules, values and expectations. Since 2008, many farmers in the region have planted one brand of seeds en masse, with some brands being planted by more than half the cotton farmers in the area. Yet the following year, they abandon these seeds in favor of a new brand, justifying their choices in hopes of achieving "manci digubadi," or good yield. As a social scientist, Flachs saw this as a testable question."The line that came up constantly was, 'I'm doing this to achieve a good yield,'" Flachs said. "That makes sense if you don't think about it too much, but four years in, I had data saying actually this decision has nothing to do with yield."Yields for the six most popular seeds during the study period were all within the normal range of variation for cotton as a whole, even as farmers repeatedly abandoned and adopted new seeds. This suggests that farmers don't have a reliable measure for what constitutes a good yield, or at least that they can't reach their desired potential because of the inherent variability of external factors such as weather, water and pests.What, then, drives these farmers' seed choices? Flachs argues that when they say they're pursuing a good yield, they're actually chasing a piece of India's success story."Using genetically modified seeds they see in flashy advertisements is their way of performing their modernity. It's something they see people doing in the rich villages," he said. "They're using technology to be as successful as they can so that they can help their families. That's at the core of how people are making these agricultural decisions -- it doesn't have to do with yields, or economic payoff, or agronomy -- in this particular context, what's making and breaking Indian agriculture and GMOs in the developing world is people reckoning with being good farmers, good parents, good members of the community. It's entirely a social decision."The best thing Indian policy-makers could do to help these farmers, Flachs said, is to slow down or regulate the influx of new seeds each season. There needs to be a way to reduce anxiety and choice-overload associated with agricultural decisions."But if we understand this as more of an existential question, then this isn't really about seeds at all. We need to improve the quality of life for Indian cotton farmers, whether that means better roads or more reliable irrigation, both of which are huge problems in India," Flachs said. "Cotton agriculture has grown with the introduction of genetically modified seeds, and people have put a lot of money into growing them, which has created a lot of debt. This is a social problem about justice, not just an agricultural problem about crop pests."
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Genetically Modified
| 2,019 |
February 21, 2019
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https://www.sciencedaily.com/releases/2019/02/190221130305.htm
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Using E. coli to create bioproducts, like biodiesel, in a cost-effective manner
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Who knew a potentially deadly bacteria could be used for good?
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LSU Mechanical Engineering graduate student Tatiana Mello of Piracicaba, Brazil, is currently working on genetically engineering and optimizing Mello proposes using "The main feedstocks used in the U.S. for biodiesel are soybean and corn oil," she said. "The actual production is enough to feed us, but you have the surplus that nobody knew what to do with, so biodiesel was created. This market is growing and growing. They expect within a few decades, the surplus won't be enough to produce biodiesel. Mello's main goal is to create Malonyl-CoA bioproducts, such as biodiesel, plastics, polymers, and pharmaceuticals. Malonyl-CoA is found in bacteria from humans and has important roles in regulating fatty acid metabolism and food intake; it's also an attractive target for drug discovery."Malonyl-CoA maximization is the topic of my research because it's a precursor for so many things," she said.Mello, who has worked on this project for two years, had the privilege of presenting her project at the National Biodiesel Conference and Expo in San Diego last month. Only 12 university-level science majors in the country who are interested in learning about the biodiesel industry receive travel scholarships to attend. However, only four of those students are asked to present their research.Mello did so as part of the Next Generation Scientists for Biodiesel, of which she is a member. She said attending the conference not only impacted her career and research, but also her understanding of the biodiesel industry."I was opened up to a new world after the misconception about the food industry and the biofuel industry competing for cropland was demystified," she said. "The many new concepts, regulations, and issues presented during the fast-paced event prepared me much better for the entire biodiesel business."After earning her bachelor's degree in biological sciences at the University of Campinas (Unicamp) in São Paulo, Mello decided she needed one more degree in order to apply her scientific knowledge."First I got into biology because I was all about studying life," she said. "It fascinated me. When I was finishing my biology degree, I realized I couldn't apply anything to what I was studying. Those were the engineers. I needed bioreactors and machinery. So, I decided to get an engineering degree."Mello stayed at Unicamp, where she earned her ME degree and then began working for Caterpillar Inc. in Brazil."While there, I realized I wanted to combine my two bachelor degrees," Mello said.She connected with LSU ME Professor Marcio de Queiroz, who is also from Brazil and now serves as her advisor. She also has co-advisors, such as LSU Biological Sciences Professor Grover Waldrop, and says they all work together and have submitted a patent on her project.Mello is set to graduate from LSU in May and plans to stay in southeast Louisiana, hopefully finding a job in the Baton Rouge area. Of course, it all depends on which company will be open to her new idea."We have this method, and it's working, but we need industry partners to scale it up," she said.
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Genetically Modified
| 2,019 |
February 19, 2019
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https://www.sciencedaily.com/releases/2019/02/190219111643.htm
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Gene therapy durably reverses congenital deafness in mice
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In collaboration with the universities of Miami, Columbia and San Francisco, scientists from the Institut Pasteur, Inserm, CNRS, Collège de France, Sorbonne University and the University of Clermont Auvergne have managed to restore hearing in an adult mouse model of DFNB9 deafness -- a hearing disorder that represents one of the most frequent cases of congenital genetic deafness. Individuals with DFNB9 deafness are profoundly deaf as they are deficient in the gene coding for otoferlin, a protein which is essential for transmitting sound information at the auditory sensory cell synapses. By carrying out an intracochlear injection of this gene in an adult DFNB9 mouse model, the scientists successfully restored auditory synapse function and hearing thresholds to a near-normal level. These findings, published in the journal
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Over half of nonsyndromic profound congenital deafness cases have a genetic cause, and most (~80%) of these cases are due to autosomal recessive forms of deafness (DFNB). Cochlear implants are currently the only option for recovering hearing in these patients.Adeno-associated viruses (AAVs) are among the most promising vectors for therapeutic gene transfer to treat human diseases. AAV-based gene therapy is a promising therapeutic option for treating deafness but its application is limited by a potentially narrow therapeutic window. In humans, inner ear development is completed in utero and hearing becomes possible at approximately 20 weeks of gestation. In addition, genetic forms of congenital deafness are generally diagnosed during the neonatal period. Gene therapy approaches in animal models must therefore take this into account, and gene therapy efficacy must be demonstrated following a gene injection when the auditory system is already in place. In other words, therapy must reverse existing deafness. The team led by Saaïd Safieddine, a CNRS researcher in the Genetics and Physiology of Hearing Unit (Institut Pasteur/ Inserm) and coordinator of the project, used a mouse model of DFNB9, a form of human deafness that represents 2 to 8% of all cases of congenital genetic deafness.DFNB9 deafness is caused by mutations in the gene coding for otoferlin, a protein that plays a key role in transmitting sound information at the inner hair cell synapses . Mutant mice deficient in otoferlin are profoundly deaf as these synapses fail to release neurotransmitters in response to sound stimulation, despite the absence of detectable sensory epithelial defects. DFNB9 mice therefore constitute an appropriate model for testing the efficacy of viral gene therapy when it is administered at a late stage. However, as AAVs have limited DNA packaging capacity (approximately 4.7 kilobase (kb)), it is difficult to use this technique for genes whose coding region (cDNA) exceeds 5 kb, such as the gene coding for otoferlin, which has a 6 kb coding region. The scientists have overcome this limitation by adapting an AAV approach known as dual AAV strategy because it uses two different recombinant vectors, one containing the 5'-end and the other the 3'-end of the otoferlin cDNA.A single intracochlear injection of the vector pair in adult mutant mice was used to reconstruct the otoferlin coding region by recombining 5' and 3'-end DNA segments, leading to long-term restoration of otoferlin expression in the inner hair cells, and then restored hearing.The scientists have therefore obtained initial proof of the concept of viral transfer of fragmented cDNA in the cochlea using two vectors, showing that this approach can be used to produce otoferlin and durably correct the profound deafness phenotype in mice.The outcomes achieved by the scientists suggest that the therapeutic window for local gene transfer in patients with DFNB9 congenital deafness could be wider than thought, and offers hope of extending these findings to other forms of deafness. These results are the subject of a patent application filed.In addition to the institutions mentioned in the first paragraph, this research was funded by the French Foundation for Medical Research, the European Union (TREAT RUSH) and the French National Research Agency (EargenCure and Lifesenses LabEx).
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Genetically Modified
| 2,019 |
February 18, 2019
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https://www.sciencedaily.com/releases/2019/02/190218153211.htm
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Plants short-cut evolution by taking genes from neighbors
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Scientists have discovered that grasses are able to short cut evolution by taking genes from their neighbours.
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The findings suggest wild grasses are naturally genetically modifying themselves to gain a competitive advantage.Understanding how this is happening may also help scientists reduce the risk of genes escaping from GM crops and creating so called "super-weeds" -- which can happen when genes from GM crops transfer into local wild plants, making them herbicide resistant.Since Darwin, much of the theory of evolution has been based on common descent, where natural selection acts on the genes passed from parent to offspring. However, researchers from the Department of Animal and Plant Sciences at the University of Sheffield have found that grasses are breaking these rules. Lateral gene transfer allows organisms to bypass evolution and skip to the front of the queue by using genes that they acquire from distantly related species."Grasses are simply stealing genes and taking an evolutionary shortcut," said Dr Luke Dunning."They are acting as a sponge, absorbing useful genetic information from their neighbours to out compete their relatives and survive in hostile habitats without putting in the millions of years it usually takes to evolve these adaptations."Scientists looked at grasses -- some of the most economically and ecologically important plants on Earth including many of the most cultivated crops worldwide such as: wheat, maize, rice, barley, sorghum and sugar cane.The paper, published in the journal Studying the genome of the grass "We also collected samples of "Counterfeiting genes is giving the grasses huge advantages and helping them to adapt to their surrounding environment and survive -- and this research also shows that it is not just restricted to "This research may make us as a society reconsider how we view GM technology as grasses have naturally exploited a similar process."Eventually, this research may also help us to understand how genes can escape from GM crops to wild species or other non-GM crops, and provide solutions to reduce the likelihood of this happening.""The next step is to understand the biological mechanism behind this phenomenon and we will carry out further studies to answer this."The research received funding from the European Research Council (ERC) Natural Environmental Research Council (NERC) and the Royal Society.
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Genetically Modified
| 2,019 |
February 4, 2019
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https://www.sciencedaily.com/releases/2019/02/190204114607.htm
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Harvesting wild genes gives crops renewed resistance to disease
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A global alliance of researchers has pioneered a new method to rapidly recruit disease-resistance genes from wild plants for transfer into domestic crops. The technique promises to revolutionise the development of disease-resistant varieties for the global food supply.
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The technique called AgRenSeq was developed by scientists at the John Innes Centre in Britain working with colleagues in Australia and the US. It was published today in The result speeds up the fight against pathogens that threaten global food crops, including wheat, soyabean, maize, rice and potato, which form the vast bulk of cereals in the human diet.Professor Harbans Bariana from the Sydney Institute of Agriculture and the School of Life and Environmental Sciences is a global expert in cereal rust genetics and a co-author of the paper.He said: "This technology will underpin fast-tracked discovery and characterization of new sources of disease resistance in plants."The current research builds on previous collaborative work done by Professor Bariana with the CSIRO and John Innes Centre. It used two wheat genes cloned by this international team as controls and Professor Bariana conducted the phenotype assessments for the study.AgRenSeq lets researchers search a library of resistance genes discovered in wild relatives of modern crops so they can rapidly identify sequences associated with disease fighting capability.From there researchers can use laboratory techniques to clone the genes and introduce them into elite varieties of domestic crops to protect them against pathogens and pests such as rusts, powdery mildew and Hessian fly.Dr Brande Wulff, a crop genetics project leader at the John Innes Centre and a lead author of the study, said: "We have found a way to scan the genome of a wild relative of a crop plant and pick out the resistance genes we need: and we can do it in record time. This used to be a process that took 10 or 15 years and was like searching for a needle in a haystack."We have perfected the method so that we can clone these genes in a matter of months and for just thousands of dollars instead of millions."The research reveals that AgRenSeq has been successfully trialled in a wild relative of wheat -- with researchers identifying and cloning four resistance genes for the devastating stem rust pathogen in the space of months. This process would easily take a decade using conventional means.The work in wild wheat is being used as a proof of concept, preparing the way for the method to be utilised in protecting many crops which have wild relatives including, soyabean, pea, cotton, maize, potato, wheat, barley, rice, banana and cocoa.Modern elite crops have, in the search for higher yields and other desirable agronomic traits, lost a lot of genetic diversity especially for disease resistance.Reintroducing disease resistance genes from wild relatives is an economic and environmentally sustainable approach to breeding more resilient crops. However, introgression of these genes into crops is a laborious process using traditional breeding methods.The new method combines high-throughput DNA sequencing with state-of-the-art bioinformatics."What we have now is a library of disease resistance genes and we have developed an algorithm that enables researchers to quickly scan that library and find functional resistance genes," said Dr Sanu Arora, the first author of the paper from the John Innes Centre.Dr Wulff said: "This is the culmination of a dream, the result of many year's work. Our results demonstrate that AgRenSeq is a robust protocol for rapidly discovering resistance genes from a genetically diverse panel of a wild crop relative," he said."If we have an epidemic, we can go to our library and inoculate that pathogen across our diversity panel and pick out the resistance genes. Using speed cloning and speed breeding we could deliver resistance genes into elite varieties within a couple of years, like a phoenix rising from the ashes."
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Genetically Modified
| 2,019 |
January 31, 2019
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https://www.sciencedaily.com/releases/2019/01/190131113901.htm
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Bacteria promote lung tumor development, study suggests
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MIT cancer biologists have discovered a new mechanism that lung tumors exploit to promote their own survival: These tumors alter bacterial populations within the lung, provoking the immune system to create an inflammatory environment that in turn helps the tumor cells to thrive.
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In mice that were genetically programmed to develop lung cancer, those raised in a bacteria-free environment developed much smaller tumors than mice raised under normal conditions, the researchers found. Furthermore, the researchers were able to greatly reduce the number and size of the lung tumors by treating the mice with antibiotics or blocking the immune cells stimulated by the bacteria.The findings suggest several possible strategies for developing new lung cancer treatments, the researchers say."This research directly links bacterial burden in the lung to lung cancer development and opens up multiple potential avenues toward lung cancer interception and treatment," says Tyler Jacks, director of MIT's Koch Institute for Integrative Cancer Research and the senior author of the paper.Chengcheng Jin, a Koch Institute postdoc, is the lead author of the study, which appears in the Jan. 31 online edition of Lung cancer, the leading cause of cancer-related deaths, kills more than 1 million people worldwide per year. Up to 70 percent of lung cancer patients also suffer complications from bacterial infections of the lung. In this study, the MIT team wanted to see whether there was any link between the bacterial populations found in the lungs and the development of lung tumors.To explore this potential link, the researchers studied genetically engineered mice that express the oncogene Kras and lack the tumor suppressor gene p53. These mice usually develop a type of lung cancer called adenocarcinoma within several weeks.Mice (and humans) typically have many harmless bacteria growing in their lungs. However, the MIT team found that in the mice engineered to develop lung tumors, the bacterial populations in their lungs changed dramatically. The overall population grew significantly, but the number of different bacterial species went down. The researchers are not sure exactly how the lung cancers bring about these changes, but they suspect one possibility is that tumors may obstruct the airway and prevent bacteria from being cleared from the lungs.This bacterial population expansion induced immune cells called gamma delta T cells to proliferate and begin secreting inflammatory molecules called cytokines. These molecules, especially IL-17 and IL-22, create a progrowth, prosurvival environment for the tumor cells. They also stimulate activation of neutrophils, another kind of immune cell that releases proinflammatory chemicals, further enhancing the favorable environment for the tumors."You can think of it as a feed-forward loop that forms a vicious cycle to further promote tumor growth," Jin says. "The developing tumors hijack existing immune cells in the lungs, using them to their own advantage through a mechanism that's dependent on local bacteria."However, in mice that were born and raised in a germ-free environment, this immune reaction did not occur and the tumors the mice developed were much smaller.The researchers found that when they treated the mice with antibiotics either two or seven weeks after the tumors began to grow, the tumors shrank by about 50 percent. The tumors also shrank if the researchers gave the mice drugs that block gamma delta T cells or that block IL-17.The researchers believe that such drugs may be worth testing in humans, because when they analyzed human lung tumors, they found altered bacterial signals similar to those seen in the mice that developed cancer. The human lung tumor samples also had unusually high numbers of gamma delta T cells."If we can come up with ways to selectively block the bacteria that are causing all of these effects, or if we can block the cytokines that activate the gamma delta T cells or neutralize their downstream pathogenic factors, these could all be potential new ways to treat lung cancer," Jin says.Many such drugs already exist, and the researchers are testing some of them in their mouse model in hopes of eventually testing them in humans. The researchers are also working on determining which strains of bacteria are elevated in lung tumors, so they can try to find antibiotics that would selectively kill those bacteria.The research was funded, in part, by a Lung Cancer Concept Award from the Department of Defense, a Cancer Center Support (core) grant from the National Cancer Institute, the Howard Hughes Medical Institute, and a Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award.
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Genetically Modified
| 2,019 |
January 30, 2019
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https://www.sciencedaily.com/releases/2019/01/190130175612.htm
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Vaccination with Streptococcus mitis could protect against virulent sibling, Streptococcus pneumonia
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Vaccinating laboratory mice with
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The investigators intranasally vaccinated mice with two different versions of Vaccination with the IgG is an important antibody in the blood and other bodily fluids, and IgA is critical in secretions, especially those of the mucus epithelium of the intestinal and respiratory tracts. Th17 cells are pro-inflammatory cells that play an important role in fighting invading pathogens.The engineered vaccine worked as expected, boosting protection against Co-corresponding author Sudhanshu Shekhar, PhD, a postdoctoral researcher in Dr. Petersen's group, noted that one must be cautious in extrapolating results from mouse models to humans, and emphasized that protection of humans would remain hypothetical until human studies have been performed.The report also noted that commensal live vaccines circumvent the main limitation of vaccinations with attenuated live pathogens: reversion to virulence."Bacterial live vaccines can be highly efficient because they mimic the natural infection," said Dr. Petersen. "They have been known for decades to prevent respiratory and enteric infections in humans. The main challenge, however, is to engineer attenuated versions that are safe as vaccines, but still offering protection. Our study reveals that
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Genetically Modified
| 2,019 |
January 29, 2019
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https://www.sciencedaily.com/releases/2019/01/190129093709.htm
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Engineering a cancer-fighting virus
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An engineered virus kills cancer cells more effectively than another virus currently used in treatments, according to Hokkaido University researchers.
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Hokkaido University researchers have engineered a virus that selectively targets and kills cancer cells. The virus, called dl355, has an even stronger anticancer effect than another engineered virus currently used in clinical practice, according to a study published in the journal Molecular oncologist Fumihiro Higashino and colleagues deleted a gene involved in viral replication, called E4orf6, from a type of adenovirus. The team previously discovered that E4orf6 stabilizes a type of mRNA called ARE-mRNAs in the infected cells enabling viral replication. ARE-mRNAs are known to be stable in stressed cells and cancer cells, but rapidly degrade in normal cells.In laboratory tests, they found that their modified adenovirus, called dl355, replicated and increased its number significantly more in cancer cells than it did in normal cells. Higashino explains "The E4orf6-lacking virus relies on the stable ARE-mRNAs in cancer cells for its replication."Some viruses can be used to treat cancers, as they replicate within the cells until they burst and die. The researchers infected several types of cultured cancer cells with 100 dl355 virus particles per cell and found that nearly all the cancer cells died within seven days. In contrast, most normal cells infected with the virus did not die, even after seven days. Several cancer cell lines managed to survive low doses of dl355, but all cancer cells were killed by the virus as the dose was increased. Tumour growth was also significantly suppressed when dl355 was administered to human tumour cells grown in mice.Finally, the team compared the anticancer effects of dl355 with another anticancer adenovirus currently used in clinical practice, called dl1520. dl355 replication was higher in all cancer cell lines tested, including cervical and lung cancer cells, and was better at killing all but one type of cancer cell, compared to dl1520. Both viruses only killed very few normal cells.The findings suggest that dl355 has potential to be an effective anticancer treatment, the team concludes. They suggest enhancing the stabilization of ARE-mRNAs in cancer cells could even further strengthen its effect, but Professor Higashino notes that further research is required. "While we think dl355 has the potential to be an effective treatment method in dealing with many types of cancers, much more research needs to be done. When we think of a timeline, at least five more years of further research may be required, possible more, on top of clinical trials," Professor Higashino noted.
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Genetically Modified
| 2,019 |
January 27, 2019
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https://www.sciencedaily.com/releases/2019/01/190127230835.htm
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Hens that lay human proteins in eggs offer future therapy hope
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Chickens that are genetically modified to produce human proteins in their eggs can offer a cost-effective method of producing certain types of drugs, research suggests.
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The study -- which has initially focused on producing high quality proteins for use in scientific research -- found the drugs work at least as well as the same proteins produced using existing methods.High quantities of the proteins can be recovered from each egg using a simple purification system and there are no adverse effects on the chickens themselves, which lay eggs as normal.Researchers say the findings provide sound evidence for using chickens as a cheap method of producing high quality drugs for use in research studies and, potentially one day, in patients.Eggs are already used for growing viruses that are used as vaccines, such as the flu jab. This new approach is different because the therapeutic proteins are encoded in the chicken's DNA and produced as part of the egg white.The team have initially focused on two proteins that are essential to the immune system and have therapeutic potential -- a human protein called IFNalpha2a, which has powerful antiviral and anti-cancer effects, and the human and pig versions of a protein called macrophage-CSF, which is being developed as a therapy that stimulates damaged tissues to repair themselves.Just three eggs were enough to produce a clinically relevant dose of the drug. As chickens can lay up to 300 eggs per year, researchers say their approach could be more cost-effective than other production methods for some important drugs.Researchers say they haven't produced medicines for use in patients yet but the study offers proof-of-principle that the system is feasible and could easily be adapted to produce other therapeutic proteins.Protein-based drugs, which include antibody therapies such as Avastin and Herceptin, are widely used for treating cancer and other diseases.For some of these proteins, the only way to produce them with sufficient quality involves mammalian cell culture techniques, which are expensive and have low yields. Other methods require complex purification systems and additional processing techniques, which raise costs.Scientists have previously shown that genetically modified goats, rabbits and chickens can be used to produce protein therapies in their milk or eggs. The researchers say their new approach is more efficient, produces better yields and is more cost-effective than these previous attempts.The study was carried out at the University of Edinburgh's Roslin Institute and Roslin Technologies, a company set up to commercialise research at The Roslin Institute.The research is published in Professor Helen Sang, of the University of Edinburgh's Roslin Institute, said: "We are not yet producing medicines for people, but this study shows that chickens are commercially viable for producing proteins suitable for drug discovery studies and other applications in biotechnology."Dr Lissa Herron, Head of the Avian Biopharming Business Unit at Roslin Technologies, said: "We are excited to develop this technology to its full potential, not just for human therapeutics in the future but also in the fields of research and animal health."Dr Ceri Lyn-Adams, Head of Science Strategy, Bioscience for Health with BBSRC, said: "These recent findings provide a promising proof of concept for future drug discovery and potential for developing more economical protein-based drugs."
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Genetically Modified
| 2,019 |
January 24, 2019
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https://www.sciencedaily.com/releases/2019/01/190124141639.htm
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Noisy gene atlas to help reveal how plants 'hedge their bets' in race for survival
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As parents of identical twins will tell you, they are never actually identical, even though they have the same genes. This is also true in the plant world. Now, new research by the University of Cambridge is helping to explain why 'twin' plants, with identical genes, grown in identical environments continue to display unique characteristics all of their own.
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Plant scientists at the Sainsbury Laboratory Cambridge University (SLCU) have built a gene expression atlas that maps the 'noisy genes' of genetically identical plants. The research, published today in This is the first time that global levels of noise in gene expression has been measured in plants. The online open-access atlas (AraNoisy) will provide a resource for plant scientists around the world to study how gene expression variability influences plant survival and diversity within clonal populations. This important stepping-stone will help us to better understand how plants survive in fluctuating environments, and could eventually lead to further research in both plant conservation efforts and future crop development.Looking at the full genetic code (called the genome) of an individual plant or animal is not enough to fully understand the individual's characteristics. The way genes behave (gene expression) can differ markedly between individuals with the same genome. A gene is expressed when the genetic code of the gene is used to direct a set of reactions that synthesise a protein or other functional molecule within a cell. Copying a segment of DNA to RNA is the first step in this sequence and is called transcription. In this study, 'noise' in gene expression refers to the measured level of variation in RNA between individual plants. Measuring the variability in gene expression reveals which genes are noisier than others.Dr Sandra Cortijo, from the Locke Group at SLCU, is researching how gene expression is regulated and what causes some genes to be expressed in unpredictable ways.To examine this, Dr Cortijo took on the mammoth task of measuring global levels of noise in gene expression in a single plant species. Using genetically identical plants, she measured the expression of all their individual genes over a 24-hour period."For our model plant, we used seedlings of a small wild brassica relative, called thale cress (Arabidopsis thaliana), which is most commonly seen growing as a weed in the cracks of pavements," Dr Cortijo said. "We performed RNA-sequencing on individual seedlings every two hours over a 24-hour period and analysed the variability for 15,646 individual genes in the plant's genome."We identified that 9% (1,358 individual genes) of the genes were highly variable for at least one time point during the 24-hour period. We found that these highly variable genes fell into two sets influenced by the diurnal cycle -- genes with more variable activity at night or genes that have more variable activity during the day."As part of the study, Dr Cortijo also identified factors that might increase gene expression variability. Highly variable genes tend to be shorter, to be targeted by a higher number of other genes (transcription factors) and to be characterised by a 'closed' chromatin environment (which is an environment that allows gene expression to be altered by attaching additional molecules during the gene reading process (transcription) without actually changing a cell's DNA)."These results shed new light on the impact of transcriptional variability in gene expression regulation in plants and can be used as a foundation for further studies into how noisy genes are connected with how plants respond to their environment," Dr Cortijo said. "Plants are a wonderful system to work with when looking at how genes are regulated in response to environmental changes as they cannot move and thus have to continually sense and respond to environmental changes. The evolution of variable gene expression could increase the robustness of a plant population against varying environments without changing their genes. Understanding how plants produce and regulate this noise in gene expression will be important for the future development of more uniform performing crops and to understand how populations of wild plants can survive more frequent weather extremes due to climate change."SLCU Research Group Leader, Dr James Locke, said the data was a significant new resource for further research: "This is an important resource for scientists studying how genetically identical plants survive fluctuating environments and provides a basis for future work looking at how genetic and epigenetic factors regulate variability for individual genes."AraNoisy is a web-based tool for accessing inter-individual transcriptional variability in Arabidopsis thaliana, throughout a 24-hour diurnal cycle. Gene expression variability for individual genes of interest can be viewed at
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Genetically Modified
| 2,019 |
January 23, 2019
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https://www.sciencedaily.com/releases/2019/01/190123131727.htm
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CRISPR/Cas9 used to control genetic inheritance in mice
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Biologists at the University of California San Diego have developed the world's first CRISPR/Cas9-based approach to control genetic inheritance in a mammal.
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Scientists around the world have been using CRISPR/Cas9 in a variety of plant and animal species to edit genetic information. One approach to editing the genome can control which of the two copies of a gene is passed to the next generation. While such "active genetics" approaches have been developed in recent years in insects, creating such tools in mammals is more challenging, and testing them takes much longer due to the longer time between generations.Publishing their work January 23 in the journal "Our motivation was to develop this as a tool for laboratory researchers to control the inheritance of multiple genes in mice," said Cooper. "With further development we think it will be possible to make animal models of complex human genetic diseases, like arthritis and cancer, that are not currently possible."To demonstrate feasibility in mice, the researchers engineered an active genetic "CopyCat" DNA element into the Tyrosinase gene that controls fur color. When the CopyCat element disrupts both copies of the gene in a mouse, fur that would have been black is instead white, an obvious readout of the success of their approach. The CopyCat element also was designed so that it cannot spread through a population on its own, in contrast with CRISPR/Cas9 "gene drive" systems in insects that were built on a similar underlying molecular mechanism.Over the two-year project period, the researchers used a variety of strategies to determine that the CopyCat element could be copied from one chromosome to the other to repair a break in the DNA targeted by CRISPR/Cas9. As a result, the element that was initially present on only one of the two chromosomes was copied to the other chromosome. In one of the families, as many as 86 percent of offspring inherited the CopyCat element from the female parent instead of the usual 50 percent.The new approach worked in female mice during the production of eggs, but not during the production of sperm in males. This is possibly due to a difference in the timing of male and female meiosis, a process that normally pairs chromosomes to shuffle the genome and may assist this engineered copying event.According to UC San Diego Professor Ethan Bier, a study coauthor, the results, "open the way for various applications in synthetic biology including the modular assembly of complex genetic systems for studying diverse biological processes."Cooper and members of her lab are now springboarding off this first mammalian active genetic success -- based on a single gene -- and attempting to expand the tool to multiple genes and traits."We've shown that we can convert one genotype from heterozygous to homozygous. Now we want to see if we can efficiently control the inheritance of three genes in an animal. If this can be implemented for multiple genes at once, it could revolutionize mouse genetics," said Cooper.While the new technology was developed for laboratory research, some have envisioned future gene drives that would build on this approach in the wild for efforts to restore the balance of natural biodiversity in ecosystems overrun by invasive species, including rodents."With additional refinements, it should be possible to develop gene-drive technologies to either modify or possibly reduce mammalian populations that are vectors for disease or cause damage to indigenous species," said Bier.However, these data also indicate that technical improvements needed for practical use in the wild allow time for careful consideration of which applications of this new technology could and should be implemented. The researchers note, however, that their results demonstrate a substantial advance that might already decrease the time, cost and number of animals needed to advance biomedical research on human diseases and to understand other types of complex genetic traits."We are also interested in understanding the mechanisms of evolution," said Cooper. "For certain traits that have evolved over tens of millions of years, the number of genetic changes is greater than we can currently assemble in mice to understand what caused bat fingers to grow into a wing, for example. So we want to make lots of these active genetic tools to understand the origins of mammalian diversity."Former UC San Diego Postdoctoral Fellow Gunnar Poplawski (co-first author, now at the National University of Singapore) and Staff Research Associate Xiang-ru Xu also contributed to the study.
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Genetically Modified
| 2,019 |
January 22, 2019
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https://www.sciencedaily.com/releases/2019/01/190122125600.htm
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Effective strategies for safeguarding CRISPR gene-drive experiments
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Researchers have demonstrated for the first time how two molecular strategies can safeguard CRISPR gene drive experiments in the lab, according to a study published today in
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Their findings, first reported on bioRxiv, suggest that scientists can effectively use synthetic target sites and split drives to conduct gene drive research, without the worry of causing an accidental spread throughout a natural population.Gene drives, such as those trialled in malaria mosquitoes, are genetic packages designed to spread among populations. They do this via a process called 'drive conversion', where the Cas9 enzyme and a molecule called guide RNA (gRNA) cut at a certain site in the genome. The drive is then copied in when the DNA break is repaired."CRISPR-based gene drives have sparked both enthusiasm and deep concerns due to their potential for genetically altering entire species," explains first author Jackson Champer, Postdoctoral Fellow in the Department of Biological Statistics and Computational Biology at Cornell University, New York. "This raises the question about our ability to prevent the unintended spread of such drives from the laboratory into the natural world."Current strategies for avoiding accidental spread involve physically confining drive-containing organisms. However, it is uncertain whether this sufficiently reduces the likelihood of any accidental escape into the wild, given the possibility of human error."Two molecular safeguarding strategies have recently been proposed that go beyond simply confining research organisms. The first is synthetic target site drive, which homes into engineered genomic sites that are absent in wild organisms. The second is split drive, where the drive construct lacks a type of enzyme called the endonuclease and relies instead on one engineered into a distant site."The nature of these strategies means that they should prevent an efficient spread outside of their respective laboratory lines," Champer adds. "We wanted to see if they both had a similar performance to standard homing drives, and if they would therefore be suitable substitutes in early gene-drive research."To do this, the team designed and tested three synthetic target site drives in the fruit fly Drosophila melanogaster. Each drive targeted an enhanced green fluorescent protein (EGFP) gene introduced at one of three different sites in the genome. For split drives, they designed a drive construct that targeted the X-linked gene yellow and lacked Cas9.Their analyses revealed that CRISPR gene drives with synthetic target sites such as EGFP show similar behaviour to standard drives, and can therefore be used for most testing in place of these drives. The split drives demonstrated similar performance, and also allow for natural sequences to be targeted in situations where the use of synthetic targets is difficult. These include population-suppression drives that require the targeting of naturally occurring genes."Based on our findings, we suggest these safeguarding strategies should be adopted consistently in the development and testing of future gene drives," says senior author Philipp Messer, Assistant Professor in the Department of Biological Statistics and Computational Biology at Cornell University. "This will be important for large-scale cage experiments aimed at improving our understanding of the expected population dynamics of candidate drives. Ultimately, this understanding will be crucial for discussing the feasibility and risks of releasing successful drives into the wild, for example to reduce malaria and other vector-borne diseases."
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Genetically Modified
| 2,019 |
January 21, 2019
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https://www.sciencedaily.com/releases/2019/01/190121103348.htm
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How staying in shape is vital for reproductive success
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Cells must keep their shape and proportions to successfully reproduce through cell division, finds new research from the Francis Crick Institute and King's College London.
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The research, published in By studying yeast cells from the related Fission yeast cells are typically pill-shaped, and the tips send molecular signals which meet in the middle. The latest research found that if the cell is too round and the ends aren't far apart enough, the signals get mixed up and the cell can't tell where the middle is. When a rounded cell divides, it breaks apart off-centre, which can either tear the DNA and kill the cell or leave two copies of DNA in one cell and none in the other."If a division leaves two copies of DNA in one cell, the one without DNA will die and the one with two copies is likely to have problems when it next divides, which in human cells can lead to cancer," explains Professor Snezhka Oliferenko, research group leader at the Crick and King's. "To avoid this, it's vital that the division happens in the right place. We found that a cell's shape determines where it will divide, highlighting the crucial function of scaling at the cellular level. This helps to answer the fundamental evolutionary question of why and how organisms would evolve the ability to scale when their size changes."When yeast cells are genetically edited or fed a restricted diet, they shrink to conserve nutrients when they divide."We found that The team found that when they disabled the rga4 gene, cells lost their ability to scale so grew too 'fat' and divided off-centre. However, when these genetically-edited cells were grown in a narrow channel to keep them thin, they divided as normal."As long as the length-to-width aspect ratio is correct,
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Genetically Modified
| 2,019 |
January 17, 2019
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https://www.sciencedaily.com/releases/2019/01/190117142130.htm
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Can a critic-turned-believer sway others? The case of genetically modified foods
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What happens when a strong advocate for one side of a controversial issue in science publicly announces that he or she now believes the opposite? Does the message affect the views of those who witness it -- and if so, how?
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Although past research suggests that such "conversion messages" may be an effective persuasion technique, the actual effect of such messages has been unknown.Now, a new study from researchers at the Annenberg Public Policy Center shows that such a conversion message can influence public attitudes toward genetically modified (GM) foods.Using video of a talk by the British environmentalist Mark Lynas about his transformation from an opponent of GM crops to an advocate, researchers found that Lynas' conversion narrative had a greater impact on the attitudes of people who viewed it than a direct advocacy message."People exposed to the conversion message rather than a simple pro-GM message had a more favorable attitude toward GM foods," said Benjamin A. Lyons, a former postdoctoral fellow at the Annenberg Public Policy Center (APPC) of the University of Pennsylvania. "The two-sided nature of the conversion message -- presenting old beliefs and then refuting them -- was more effective than a straightforward argument in favor of GM crops.""Conversion messages and attitude change: Strong arguments, not costly signals" was published in January 2019 in the journal In 2013, Lynas, a journalist and activist who had opposed GM crops, spoke at the Oxford Farming Conference about his change of belief. In the current experiment, APPC researchers used video excerpts from Lynas' talk to more than 650 U.S. adult participants, who competed a survey about it.The respondents each were shown one of three video clips: 1) Lynas explaining the benefits of GM crops; 2) Lynas discussing his prior beliefs and changing his mind about GM crops; and 3) Lynas explaining why his beliefs changed, including the realization that the anti-GM movement he helped to lead was a form of anti-science environmentalism.The researchers found that both forms of the conversion message (2 and 3) were more influential than the simple advocacy message. There was no difference in impact between the basic conversion message and the more elaborate one.Measuring how the conversion narrative worked, the researchers found that it enhanced Lynas' "perceived argument strength," rather than bolstering his personal credibility, which they found an important distinction. The fact that argument strength served as a mediator on GM attitudes supports the idea that "the unexpected shift in the position of the speaker ... prompted central or systematic processing of the argument," which, in turn, implies a more durable change in attitudes.Unlike other controversial issues in science such as evolution or climate change, Americans' views on GM crops do not seem to be related to political ideology or religious beliefs. Nor are Americans especially knowledgeable about GM foods -- one prior study found that only 43 percent of Americans know that GM foods are available for human consumption and only 26 percent believe that they have eaten food that was genetically modified. In another earlier study, 71 percent of Americans say they have heard little or nothing about GM foods -- yet 39 percent think GM foods present a risk to human health.Given that many Americans' views on genetically modified foods aren't yet fixed by group values and motivated reasoning, their minds may be more easily changeable on this issue. Lyons said it may be possible to present scientific evidence through a conversion narrative to people on such low-knowledge, lower-profile issues and affect their views."After completing this study, I'm more optimistic about our ability to change minds on the issues that haven't been totally polluted by ideology," Lyons said.The researchers cautioned that the findings may not extend beyond an American audience, and said that their audience included many who did not have strong pro- or anti-GM attitudes. They said conversion messaging should be tested with people who do have strong pre-existing views on GM foods. They also noted that this research tested a conversion in only one direction -- from anti-GM to pro-GM foods -- and said it would be valuable to explore the opposite case.
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Genetically Modified
| 2,019 |
January 16, 2019
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https://www.sciencedaily.com/releases/2019/01/190116090630.htm
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Born to run: Just not on cocaine
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Cocaine is a highly addictive psychostimulant that induces complex molecular, cellular and behavioral responses. Despite various approaches and years of pre-clinical studies, effective, mechanism-based therapies to assist with cocaine misuse and dependence are still sorely lacking. Although it is well understood that elevations of the brain chemical dopamine play a critical role in cocaine's ability to produce a "high" -- feelings that trigger the spiral into addiction -- the actions of cocaine are far more complex.
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Dopamine signaling dysfunction also is believed to contribute to multiple neuropsychiatric disorders including attention-deficit/hyperactivity disorder (ADHD). Although significant evidence exists of disrupted dopamine signaling in these disorders, the mechanisms by which these changes arise, and the impact that these insults have on synaptic and circuit plasticities, remain an active area of investigation. Importantly, individuals with ADHD who have not received treatment are at an increased risk for substance use disorder.Using a unique strain of genetically engineered mice, a team of neuroscientists at Florida Atlantic University's Brain Institute and collaborators at Vanderbilt University and the Research Triangle Institute, Research Triangle Park, have discovered a surprising response to cocaine in these mice.Results from the study, published in the journal The study was spearheaded by Randy D. Blakely, Ph.D., lead author, executive director of FAU's Brain Institute, and a professor of biomedical science in FAU's Schmidt College of Medicine.Several years ago, Blakely and his team generated DAT Val559 mice, named for their expression of a rare human genetic variant (Val559) that alters the function of the dopamine transporter (DAT). DAT proteins are responsible for limiting the signaling of dopamine in the brain by sweeping the neurotransmitter away from synapses.Blakely initially identified the DAT Val559 mutation in subjects with ADHD. Others found the genetic variant in subjects with autism and bipolar disorder. The gene variant also has been found in apparently normal subjects, suggesting a complex mode of action."It was extremely odd to see a mouse given cocaine not to become hyperactive, and it suggested to us that an unexpected change had occurred in the brain in response to the mutation, a change that might be worth identifying," said Blakely. "Adding more to the puzzle, we found that the DAT Val559 mice responded with a hyperactive response to other psychostimulants such as amphetamine or methylphenidate like Ritalin™."Cocaine, unlike amphetamine and methylphenidate, exhibits a potent interaction with the serotonin (5-HT) transporter (SERT), a sister protein of DAT. SERT sweeps away serotonin at synapses just like DAT does for dopamine. Blakely's team believes that during brain development the altered dopamine signaling arising in the DATVal559 mice triggered a change in the strength of serotonin actions, specifically in brain circuits that impact the activation of movement and the ability to shake off drug memories. When the researchers limited serotonin's actions with a serotonin blocker, the mice regained a normal hyperactive response to cocaine."We previously found increased reward motivation in the DAT Val559 mice, and attributed these responses to changes in dopamine for obvious reasons," said Adele Stewart, Ph.D., first author of the study and a post-doc in Blakely's lab. "Our studies with cocaine, however, revealed something more interesting -- basically that developmental changes in dopamine handling lead to remarkably powerful changes in the brain's use of serotonin. This makes us wonder if children developing with excessive dopamine signaling might benefit from medications that target serotonin neurons and their synapses."According to Florida's Medical Examiner Commission, overdose deaths from cocaine are at their highest level in the state since 2007. From 2012 to 2015, cocaine deaths in Florida increased from 1,318 fatalities to 1,834 fatalities. Only fentanyl, a powerful synthetic painkiller, surpassed deaths from cocaine overdose in Florida.Nationally, more than 1 in 3 drug misuse or abuse-related emergency department visits (40 percent) involved cocaine."Although we were initially focused on the significance of our work in relation to ADHD, we think that there may be some very important lessons here that could help those dealing with substance use disorder," said Blakely.
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Genetically Modified
| 2,019 |
January 15, 2019
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https://www.sciencedaily.com/releases/2019/01/190115121100.htm
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MANF identified as a rejuvenating factor in parabiosis
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Older mice who are surgically joined with young mice in order to share a common bloodstream get stronger and healthier, making parabiosis one of the hottest topics in age research. Publishing in
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"We know that MANF, which regulates metabolism and immune response in flies, mice and humans, declines with age," said senior author Heinrich Jasper, PhD, a Buck professor and staff scientist at Genentech. "This research shows that replenishing MANF has promise as an anti-aging treatment although much work remains to be done in order to understand its mechanism of action."While researchers have yet to understand why MANF levels decrease with age, Jasper says MANF deficiency has obvious hallmarks. Flies genetically engineered to express less MANF suffered from increased inflammation and shorter lifespans. MANF-deficient mice had increased inflammation in many tissues as well as progressive liver damage and fatty liver disease. Older mice who shared blood with MANF-deficient younger mice did not benefit from the transfusion of young blood.Buck postdoctoral fellows Pedro Sousa-Victor, PhD, and Joana Neves, PhD, were co-leaders of the study. They zeroed in on MANF and its impact on the liver and metabolism. They found that liver rejuvenation spurred by parabiosis was dependent on MANF. In addition, they showed that supplementing MANF in aging mice slowed liver aging, prevented fatty liver disease in animals on a high fat diet and improved age-related metabolic dysfunction."MANF appears to regulate inflammatory pathways that are common to many age-related diseases," said Neves. "We are hoping its effects extend beyond the liver, we plan to explore this in other tissues.""The search for systemic treatments that would broadly delay or prevent age-related diseases remains the holy grail of research in aging," said Jasper. "Given that MANF appears to modulate the immune system, we are excited to explore the larger implications of its therapeutic use. We are also cautious. There are many tissues and organ systems to evaluate in terms of MANF and we have yet to determine its effects on lifespan in the mouse."
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Genetically Modified
| 2,019 |
January 14, 2019
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https://www.sciencedaily.com/releases/2019/01/190114161140.htm
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Study: 'Post-normal' science requires unorthodox communication strategies
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Proposals to fight malaria by "driving" genes that slow its spread through mosquitoes is a high-risk, high-reward technology that presents a challenge to science journalists, according to a new report aimed at stimulating a fruitful, realistic public discussion of "post-normal" science and technology.
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Post-normal science is a new term for technologies where the usual expertise is not enough to evaluate costs, benefits and safety.A debate on a technique to control malaria with genetic manipulation could spark the kind of polarized arguments that persist decades after the introduction of genetically modified (GM) corn, soy and cotton.Inhibiting malaria could reduce the toll of death and disease. The World Health Organization estimated that the mosquito-borne parasite caused 429,000 deaths among 212 million cases in 2015.The new technology of "gene drives" raises the ante on existing uses of GM organisms, says Dominique Brossard, corresponding author of "Promises and Perils of Gene Drives," published this week in the Brossard's scholarship occurs at the intersection of science, media and policy. She chairs the department of life science communication at the University of Wisconsin-Madison.Advocates of "gene drives" propose to battle malaria by creating and distributing genetically engineered mosquitoes that prevent them, and their offspring, from transmitting malaria. One tactic could rely on genes that cause the insect's immune system to kill malaria parasites.Beyond diseases carried by vectors, the technology might be applied to reducing populations of invasive species.Other examples of post normal science include two areas currently in the headlines: climate change and human gene editing. News of the birth of two babies from an embryo that was supposedly subjected to gene editing highlights the need to discuss post-normal technologies, Brossard says. "I would characterize this case as illicit, unregulated, unproven, questionable, unnecessary... and perhaps a harbinger of the future."Smart, effective regulation of post-normal science, the PNAS authors argue, requires accounting for a mix of scientific, social, religious, ethical and environmental viewpoints.The new analysis grew from the Third Sackler Colloquium on The Science of Science Communication, and was performed by Brossard, Pam Belluck, a science journalist at The New York Times, and Fred Gould, a professor of agriculture with a specialty in entomology at North Carolina State University."Our aim," the authors write, "is therefore to use our collective experiences and knowledge to highlight how the current debate about gene drives could benefit from lessons learned from other contexts and sound communication approaches involving multiple actors."Existing regulations on the release of genetically engineered organisms were "developed for crop plants and animals that typically don't spread on their own in the environment," Brossard's group notes.But even though genetic engineering is now deeply embedded in corn, soy and cotton planted on hundreds of millions of acres, those crop seeds are not to be replanted, and so the novel genes are not supposed to spread.In gene drives, however, success depends on having the GM genes spread broadly in target populations. Thus, gene drives are fraught with a panoply of hazards, real or false, predicted, unpredicted or unimagined.Part of the difficulty emerges from the accelerating pace of science, Brossard says. "If something stays in the lab for a long time, there may be time for discussions about regulation, but now science gets out so fast that the capacity for society to deal with it may lag behind."And in the social-media era, headlines -- scary or promising, accurate or otherwise -- instantly rocket around the world.The issue of gene drives has become even more pertinent with the advent of a fast, precise "gene editing" tool called CRISPR. "We found that efforts to drive genes into wild mosquitoes or other organisms are both exciting and scary," the PNAS authors wrote.A cautionary example about the perils of "post-normal" science surrounds the introduction of genetic engineering technology more than 40 years ago. The new technology seemed threatening, even to some insiders, and scientists voluntarily suspended research in 1975, then held a conference at Asilomar, Calif., to discuss safety limits.Asilomar is sometimes cited as a success, yet controversy persists over releases of GM organisms. "Asilomar was a great example of an issue that was not approached with what we call the post-normal paradigm," says Brossard. "It was approached as 'Scientists know the best way to move forward,' and that is responsible to some extent for what we see today, a very polarized view about GM organisms. As a result, some of the African countries that need them most are not always able to use them."Given that cautionary history, she says, "This is our warning: Let's be careful not to make the same mistake. We need to consider social, ethical and economic dimensions; it's not only the technical aspects of the technology that matters when you think risks and benefits."Gene editing, gene drives and other impending post-normal technologies offer a chance for a do-over, Brossard says. "Can we develop a middle ground for assessing the situation? How could this technology be useful? What would it mean to use this responsibly? What are its risks and for whom?"One sign of progress, Brossard says, "would be the absence of something we had in the GM debate, two extremely vocal, polarized sides. GM crops are not a magic-bullet technology that is going to save the world -- or destroy it, either. All technologies have risks and benefits, and genetic engineering is the same. It still needs regulation."Smart regulation is accepted with older innovations, Brossard says. "Automobiles are a powerful technology. If we did not have traffic laws, if people did not know how to drive, autos could lead to catastrophe, but with smart regulation, they are a highly useful technology."In the context of gene drives and other post-normal technologies, Brossard says, "We need to stop saying, 'We need to promote meaningful dialog.' We need to actually go out and do it."
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Genetically Modified
| 2,019 |
January 14, 2019
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https://www.sciencedaily.com/releases/2019/01/190114114221.htm
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Genetically modified food opponents know less than they think, research finds
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The people who hold the most extreme views opposing genetically modified (GM) foods think they know most about GM food science, but actually know the least, according to new research.
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The paper, published Monday in Marketing and psychology researchers asked more than 2,000 U.S. and European adults for their opinions about GM foods. The surveys asked respondents how well they thought they understood genetically modified foods, then tested how much they actually knew with a battery of true-false questions on general science and genetics.Despite a scientific consensus that GM foods are safe for human consumption and have the potential to provide significant nutritional benefits, many people oppose their use. More than 90 percent of study respondents reported some level of opposition to GM foods.The paper's key finding is that the more strongly people report being opposed to GM foods, the more knowledgeable they think they are on the topic, but the lower they score on an actual knowledge test."This result is perverse, but is consistent with previous research on the psychology of extremism," said Phil Fernbach, the study's lead author and professor of marketing at the Leeds School of Business. "Extreme views often stem from people feeling they understand complex topics better than they do."A potential consequence of the phenomenon, according to the paper's authors, is that the people who know the least about important scientific issues may be likely to stay that way, because they may not seek out -- or be open to -- new knowledge."Our findings suggest that changing peoples' minds first requires them to appreciate what they don't know," said study co-author Nicholas Light, a Leeds School of Business PhD candidate. "Without this first step, educational interventions might not work very well to bring people in line with the scientific consensus."The paper's authors also explored other issues, like gene therapy and climate change denial. They found the same results for gene therapy.However, the pattern did not emerge for climate change denial. The researchers hypothesize that the climate change debate has become so politically polarized that people's attitudes depend more on which group they affiliate with than how much they know about the issue.Fernbach and Light plan to follow this paper with more research on how their findings play into other issues like vaccinations, nuclear power and homeopathic medicine.This research was funded by the Humility & Conviction in Public Life project at the University of Connecticut, the Center for Ethics and Social Responsibility at CU Boulder, the National Science Foundation and the Social Sciences and Humanities Research Council.
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Genetically Modified
| 2,019 |
January 10, 2019
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https://www.sciencedaily.com/releases/2019/01/190110141842.htm
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Bacteria help discover human cancer-causing proteins
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A team led by researchers at Baylor College of Medicine and the University of Texas at Austin has applied an unconventional approach that used bacteria to discover human proteins that can lead to DNA damage and promote cancer. Reported in the journal
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"Our cells make protein carcinogens," said co-corresponding author Dr. Susan M. Rosenberg, Ben F. Love Chair in Cancer Research and professor of molecular and human genetics, of molecular virology and microbiology and of biochemistry and molecular biology at Baylor. "Cancer is a disease of mutations. A normal cell that has accumulated several mutations in particular genes becomes likely to turn into a cancer cell."Mutations that cause cancer can be the result of DNA damage. External factors such as tobacco smoke and sunlight can damage DNA, but most DNA damage seems to result from events that occur within cells and is mediated by cellular components, including proteins. Despite the importance of these events, they have not been studied extensively."One way proteins can cause DNA damage is by being overproduced, which is a relatively frequent cellular event," said Rosenberg, who also is leader of the Cancer Evolvability Program at the Dan L Duncan Comprehensive Cancer Center at Baylor. "In this study, we set out to uncover proteins that, when overproduced by the cell, cause damage to DNA in ways that can lead to cancer."To uncover these DNA "damage-up" proteins, the researchers took an unconventional approach. They searched for proteins that promote DNA damage in human cells by looking at proteins that, when overproduced, would cause DNA damage in the bacterium "Although bacteria and people are different, their basic biological processes are similar, so with this approach we thought we might find common mechanisms of DNA damage that could be relevant to cancer," Rosenberg said."This was a wild idea," said Rosenberg, and was possible because of funding from two sources aimed at trying high-risk strategies that, if successful, would have high impact: a National Institutes of Health Director's Pioneer Award and a gift from the W.M. Keck Foundation, among many other grants to the 16-lab team.The researchers genetically modified bacteria so they would fluoresce red when DNA was damaged. Then, they overexpressed each of the 4,000 genes present in E coli individually and determined which ones made bacteria glow red."We uncovered an extensive and varied network of proteins that, when overproduced, alter cells in ways that lead to DNA damage," Rosenberg said. "Some of these proteins are, as expected, involved in DNA processing or repair, but, surprisingly, most are not directly connected to DNA. For instance, some of the DNA damage-up proteins participate in the transport of molecules across the cell membrane."When the researchers looked for human protein relatives of the DNA "damage-up" proteins they had found in bacteria, they identified 284. Interestingly, they determined that these human proteins are linked to cancer more often than random sets of proteins. In addition, the proteins' RNAs, an indicator of protein production, predicted mutagenesis in tumors and poor patient prognosis. When the researchers overproduced these proteins in human cells in the lab, half of the proteins triggered DNA damage and mutation."We showed that "I think it is extraordinary to identify so many ways DNA can be damaged. This study is opening up new avenues for discoveries of novel mechanisms that protect our genomes and how their dysfunction can alter the integrity of our DNA and cause cancer," said co-corresponding author Dr. Kyle M. Miller, associate professor of molecular biosciences at the University of Texas at Austin and member of the Dan L Duncan Comprehensive Cancer Center at Baylor. "It is yet another example of the power of model organisms to uncover basic biological processes that can shine a light on how human cells and cancer work.""Our work has significant implications both in basic biological fields and in clinical research," Rosenberg said. "We provide a previously unknown understanding of the diverse mechanisms that can generate DNA damage leading to cancer. In the future, this finding may lead to new ways to identify people who are likely to develop cancer so that strategies to prevent it, slow it down or catch it early can be used."The study's two co-first authors were students earning their doctorates: Dr. Jun Xia at Baylor College of Medicine and Dr. Liya Chiu at the University of Texas at Austin.For a complete list of all the contributors and their affiliations and the financial support of this study, visit the journal
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Genetically Modified
| 2,019 |
January 10, 2019
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https://www.sciencedaily.com/releases/2019/01/190110141814.htm
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Rice plants engineered to be better at photosynthesis make more rice
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A new bioengineering approach for boosting photosynthesis in rice plants could increase grain yield by up to 27%, according to a study publishing January 10 in the journal
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"Food shortage related to world population growth will be a serious problem our planet will have to face," says senior study author Xin-Xiang Peng of South China Agricultural University in Guangzhou, China. "Our study could have a major impact on this problem by significantly increasing rice yield, especially for areas with bright light."Bioengineering improvement of rice, a staple food crop worldwide, has high practical importance, particularly in light of the need for increased crop productivity due to world population growth and the reduction of cultivable soils. But increases in yield for rice and several other major crops have been sparse in recent years, and crop yield seems to be reaching a ceiling of maximal potential.The main genetic approach for increasing the yield potential of major crops focuses on photosynthesis, the biochemical process in which COOver the past few years, three photorespiratory bypasses have been introduced into plants, and two of these led to observable increases in photosynthesis and biomass yield. But most of the experiments were carried out using the model organism Arabidopsis, and the increases have typically been observed under environment-controlled, low-light, and short-day conditions. "To the best of our knowledge, our study is the first that tested photorespiration bypass in rice," says co-author Zheng-Hui He of San Francisco State University.In the new study, the researchers developed a strategy to essentially divert COAs a result, the photorespiratory rate was suppressed by 18%-31% compared to normal, and the net photosynthetic rate increased by 15%-22%, primarily due to higher concentrations of cellular COMoving forward, the researchers plan to optimize the performance of the engineered plants in the field by putting the same metabolic bypass in other rice varieties. They would also like to apply the same approach to other crop plants such potatoes."Our engineered plants could be deployed in fields at a larger scale after further evaluations by independent researchers and government agencies," Peng says. "Although we don't expect this approach would affect the taste of these plants, both the nutritional quality and taste are yet to be comprehensively evaluated by independent labs and governmental agencies."This work was supported by the National Natural Science Foundation of China and Science and Technology Project of Guangzhou City.
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Genetically Modified
| 2,019 |
January 3, 2019
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https://www.sciencedaily.com/releases/2019/01/190103142306.htm
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Scientists engineer shortcut for photosynthetic glitch, boost crop growth 40%
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Plants convert sunlight into energy through photosynthesis; however, most crops on the planet are plagued by a photosynthetic glitch, and to deal with it, evolved an energy-expensive process called photorespiration that drastically suppresses their yield potential. Researchers from the University of Illinois and U.S. Department of Agriculture Agricultural Research Service report in the journal
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"We could feed up to 200 million additional people with the calories lost to photorespiration in the Midwestern U.S. each year," said principal investigator Donald Ort, the Robert Emerson Professor of Plant Science and Crop Sciences at Illinois' Carl R. Woese Institute for Genomic Biology. "Reclaiming even a portion of these calories across the world would go a long way to meeting the 21st Century's rapidly expanding food demands -- driven by population growth and more affluent high-calorie diets."This landmark study is part of Realizing Increased Photosynthetic Efficiency (RIPE), an international research project that is engineering crops to photosynthesize more efficiently to sustainably increase worldwide food productivity with support from the Bill & Melinda Gates Foundation, the Foundation for Food and Agriculture Research (FFAR), and the U.K. Government's Department for International Development (DFID).Photosynthesis uses the enzyme Rubisco -- the planet's most abundant protein -- and sunlight energy to turn carbon dioxide and water into sugars that fuel plant growth and yield. Over millennia, Rubisco has become a victim of its own success, creating an oxygen-rich atmosphere. Unable to reliably distinguish between the two molecules, Rubisco grabs oxygen instead of carbon dioxide about 20 percent of the time, resulting in a plant-toxic compound that must be recycled through the process of photorespiration."Photorespiration is anti-photosynthesis," said lead author Paul South, a research molecular biologist with the Agricultural Research Service, who works on the RIPE project at Illinois. "It costs the plant precious energy and resources that it could have invested in photosynthesis to produce more growth and yield."Photorespiration normally takes a complicated route through three compartments in the plant cell. Scientists engineered alternate pathways to reroute the process, drastically shortening the trip and saving enough resources to boost plant growth by 40 percent. This is the first time that an engineered photorespiration fix has been tested in real-world agronomic conditions."Much like the Panama Canal was a feat of engineering that increased the efficiency of trade, these photorespiratory shortcuts are a feat of plant engineering that prove a unique means to greatly increase the efficiency of photosynthesis," said RIPE Director Stephen Long, the Ikenberry Endowed University Chair of Crop Sciences and Plant Biology at Illinois.The team engineered three alternate routes to replace the circuitous native pathway. To optimize the new routes, they designed genetic constructs using different sets of promoters and genes, essentially creating a suite of unique roadmaps. They stress tested these roadmaps in 1,700 plants to winnow down the top performers.Over two years of replicated field studies, they found that these engineered plants developed faster, grew taller, and produced about 40 percent more biomass, most of which was found in 50-percent-larger stems.The team tested their hypotheses in tobacco: an ideal model plant for crop research because it is easier to modify and test than food crops, yet unlike alternative plant models, it develops a leaf canopy and can be tested in the field. Now, the team is translating these findings to boost the yield of soybean, cowpea, rice, potato, tomato, and eggplant."Rubisco has even more trouble picking out carbon dioxide from oxygen as it gets hotter, causing more photorespiration," said co-author Amanda Cavanagh, an Illinois postdoctoral researcher working on the RIPE project. "Our goal is to build better plants that can take the heat today and in the future, to help equip farmers with the technology they need to feed the world."While it will likely take more than a decade for this technology to be translated into food crops and achieve regulatory approval, RIPE and its sponsors are committed to ensuring that smallholder farmers, particularly in Sub-Saharan Africa and Southeast Asia, will have royalty-free access to all of the project's breakthroughs.
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Genetically Modified
| 2,019 |
January 3, 2019
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https://www.sciencedaily.com/releases/2019/01/190103142236.htm
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Obese mice lose anxiety when 'zombie cells' exit their brain
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Mayo Clinic researchers and collaborators have shown in mice that obesity increases the level of "zombie" or senescent cells in the brain, and that those cells, in turn, are linked to anxiety. When senolytic drugs are used to clear those cells, the anxious behaviors in the mice dissipate. These findings appear in
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Senscent cells are just as the name zombie implies -- semidormant cells that remain in a given area of the body and, by doing so, impair other functions. Research has shown that they contribute to aspects of aging, from osteoporosis to diabetes and muscle weakness. In this case, researchers knew that obesity -- in both humans and mice -- is related to increased anxiety and other emotional issues. Yet the details of that relationship are unclear.Using genetically modified mice and normal mice, the team, which included researchers from the Mayo Clinic Robert and Arlene Kogod Center on Aging and the University of Newcastle, as well as others, determined that the study mice developed more fat cells in the brain area that controls anxiety and they had a significant increase of senescent cells in that region. Clearing the cells with senolytic drugs in the two mouse models resulted in anxious behavior ending; lipid cells in the brain disappearing; and neurogenesis, or normal neurological cell growth, resuming.How do you tell if a mouse has anxiety? A number of scientifically validated tests are used. An anxious mouse tends to avoid open areas in its environment, and tends to move only along the outside walls or corners of its enclosure. Also, anxious mice behave differently in mazes, performing poorly and with hesitation, often not completing the test. After removal of the zombie cells, the mice did much better even though they were still obese.In their paper the authors say, "Our data demonstrating a link between obesity, senescence and anxietylike behavior provide critical support for the potential feasibility of administering senolytics to treat obesity-associated anxietylike behavior, provided that clinical trials validate this approach."They say more preclinical research is needed, as well, to determine which type of senescent cells are responsible and define the mechanism of action more fully.Support for the research came from Cancer Research UK, a Newcastle University Faculty of Medical Sciences Fellowship, The Academy of Medical Sciences, The Connor Group, the National Institutes of Health, the Glenn/American Federation for Aging Research Breakthroughs in Gerontology award, Robert and Theresa Ryan, The Ted Nash Long Life and Noaber Foundations, Regenerative Medicine Minnesota, and Humor the Tumor.Researchers include first author Mikolaj Ogrodnik, Ph.D., and senior authors Diana Jurk, Ph.D., formerly of University of Newcastle and now at Mayo Clinic, and James Kirkland, M.D., Ph.D., of Mayo Clinic. The team also included researchers from Stony Brook University, Moscow Institute of Physics and Technology, University of Texas Health Sciences Center, and the Near East University, Cyprus.
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Genetically Modified
| 2,019 |
December 18, 2018
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https://www.sciencedaily.com/releases/2018/12/181218123123.htm
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Gut microbiome regulates the intestinal immune system
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Scientist have long known that bacteria in the intestines, also known as the microbiome, perform a variety of useful functions for their hosts, such as breaking down dietary fiber in the digestive process and making vitamins K and B7.
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Yet a new study unveils another useful role the microbiome plays. A team of researchers from Brown University found that in mice, the gut microbiome regulates the host's immune system -- so that rather than the host's defense system attacking these helpful bacteria, the bacteria can co-exist peacefully with the immune system.What's the trick to the microbiome's work with the immune system? Vitamin A -- the bacteria moderate active vitamin A levels in the intestine, protecting the microbiome from an overactive immune response.That insight may prove important for understanding and treating autoimmune and inflammatory diseases, said Shipra Vaishnava, an assistant professor of molecular microbiology and immunology at Brown."A lot of these diseases are attributed to increased immune response or immune activation, but we've found a new way that bacteria in our gut can dampen the immune response," Vaishnava said. "This research could be critical in determining therapies in the case of autoimmune diseases such as Crohn's disease or other inflammatory bowel diseases, as well as vitamin A deficiency."The study was published on Tuesday, Dec. 18, in the journal The gut microbiome is an ecosystem made of 100 trillion bacteria that have evolved to live in the special conditions of the intestines, Vaishnava said. The vast majority of these bacteria do not harm their hosts but are helpful instead. A healthy microbiome, just like a healthy forest, has many species co-existing together and can fend off hostile intruders -- such as disease-causing bacteria or invasive species.In both humans and mice, the phyla Firmicutes and Bacteroidetes comprise the majority of the gut microbial community. To play their part in regulating their hosts' immune systems, the bacteria in the microbiome fine-tune the levels of a protein responsible for the conversion of vitamin A to its active form in their hosts' gastrointestinal tract, the researchers found.Vaishnava's team found that Firmicutes bacteria, particularly members of the class Clostridia, reduce the expression of a protein within the cells that line the intestines. The protein, retinol dehydrogenase 7 (Rdh7) converts dietary vitamin A to its active form, retinoic acid, Vaishnava said. The Clostridia bacteria, common to both mice and men, also promote increased vitamin A storage in the liver, the team found.Vaishnava expects the findings are generalizable to the interactions between the human microbiome and their hosts as well.Mice genetically engineered to not have Rdh7 in their intestinal cells have less retinoic acid in the intestinal tissue, as the researchers expected. Specifically, the guts of the engineered mice had fewer immune cells that make IL-22, an important cellular signal that coordinates the antimicrobial response against gut bacteria. Other components of the immune system such as cells with immunoglobulin A and two types of T-cells were the same as in standard mice, suggesting Rdh7 is only essential for the regulating antimicrobial response, Vaishnava said.The researchers do not know exactly how Rdh7 is suppressed, but Clostridia bacteria are known to produce short chain fatty acids that change host gene expression. As a next step in their research, the team will study how bacteria regulate Rdh7 expression, including examining various short chain fatty acids, Vaishnava said.In addition, the team will conduct research to understand why Rdh7 suppression is critical. They are working to genetically engineer mice to always express Rdh7 in their intestinal cells. Vaishnava wants to see how this affects the mouse microbiome and if it leads to any inflammation or autoimmune disease-like conditions for the mice. They will also explore the impacts of increased vitamin A storage in the liver due to bacteria Rdh7 regulation, Vaishnava said.The researchers say that understanding how bacteria regulate the immune system's responses could be important in unlocking the keys to disorders like Crohn's disease.Data from clinical studies has shown that inflammation in the bowel is a result of disrupted interactions between a host and their gut microbiome, Vaishnava said."The role of vitamin A in inflammation is context-dependent and is very hard to tease apart," Vaishnava said. "A change in vitamin A status and vitamin A metabolic genes coincides with inflammatory bowel diseases, but we don't know if this promotes inflammation or not. We hope that adding our finding -- that bacteria can regulate how vitamin A is being metabolized in the intestine or stored -- could help clarify why the field is seeing what it is seeing."These findings could also provide clues about the importance of the microbiome in addressing vitamin A deficiency, a problem that is particularly prevalent in Africa and Southeast Asia.Vitamin A deficiency affects approximately one third of children under the age of five, according to the World Health Organization (WHO). Vitamin A deficiency weakens the immune system and increases the risk of infectious diseases. The WHO has been providing at-risk children with vitamin A supplements for the past 25 years, but it hasn't been as successful as hoped for, according to Vaishnava. This study shows bacteria are a big part of vitamin A absorption and storage and perhaps children need to have the right combination of bacteria in the gut in order for the vitamin A supplements to be most effective, she added."Both our diet and the bacteria in our gut are critically linked in regulating how our immune cells behave," Vaishnava said. "Finding what those links are at a molecular level is important to figuring out how we could use either diet or bacteria, or both of them together, to have a therapeutic effect in inflammatory or infectious diseases."
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December 17, 2018
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https://www.sciencedaily.com/releases/2018/12/181217101747.htm
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How marijuana may damage teenage brains in study using genetically vulnerable mice
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In a study of adolescent mice with a version of a gene linked to serious human mental illnesses, Johns Hopkins Medicine researchers say they have uncovered a possible explanation for how marijuana may damage the brains of some human teens.
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In a report that will be published in a 2019 print issue of the journal "The inflammation we saw in our mice is probably activated in many people who smoke marijuana, but our results may help explain why and how some mice¾and some people¾are genetically predisposed to experience an enhanced inflammatory response and brain damage," says Mikhail "Misha" Pletnikov, M.D., Ph.D, professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine."Now that marijuana is moving toward widespread legalization and recreational use, it's important to learn more about why it's not harmless to everyone," says Atsushi Kamiya, M.D., Ph.D., a co-senior author on this study and associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. "There's still a lot that we don't know about how pot specifically affects the brain."Although far more research must be done to determine if their findings apply to humans, Pletnikov says, it's already clear that heavy cannabis use is linked to long-lasting cognitive problems, but only in a percentage of those who used pot during adolescence. The challenge for scientists has been to identify the risk factors that may increase adverse effects of cannabis. Having that information, Pletnikov says, could lead to efficient preventive strategies. Building on the knowledge that only a select population of teen pot smokers have later cognitive problems, the researchers chose to experiment with a mouse model for psychiatric illnesses that carries a mutation in the DISC1 gene originally found in a Scottish family with many members diagnosed with schizophrenia, bipolar disorder and major depression.The researchers used mice that make the faulty DISC1 protein in their brains. When the mice were about 30 days old, the rodent equivalent of teenagers, the researchers injected them with 8 milligrams per kilogram D9-tetrahydrocannabinol (THC) -- the active chemical in marijuana responsible for feeling high -- every day for three weeks, somewhat mimicking the exposure from daily smoking during adolescence.Then the researchers stopped the THC exposure for three weeks before testing the mice for behavioral and cognitive deficits."Essentially, we let them have their fun as teenagers and then let enough time elapse to their young adulthood, or in human terms the time when people reach their late 20s, are living an adult life and may begin to notice cognitive problems," says Pletnikov.Mice like to explore previously unvisited places or new objects, but examine familiar places or objects much less, suggesting mice have recognition memory. For this reason, researchers often use the Y maze test or the novel object recognition test to evaluate recognition memory in mice. In the Y maze test, a maze shaped like a letter "Y," mice were initially exposed to two open arms and one blocked arm. Later, when the previously blocked arm became accessible, control mice spent more time in the previously blocked arm compared with the previously visited arms. In the novel object recognition test, mice were initially presented with two identical objects; later, one of the objects was replaced with a new one. Control mice spent much more time exploring the new object compared with the familiar one. In both tests, control mice showed good recognition memory. In contrast, male DISC1 mice exposed to THC showed deficient recognition memory as they explored the previously blocked arm of the Y maze and the new object as much as they examined the familiar arms and objects.The researchers say this indicates poorer recognition memory in the DISC1 mice exposed to marijuana. The effects of THC on recognition memory in the female DISC1 mice were less profound than in male DISC1 mice, so the researchers chose to focus on the male mice for remaining experiments."In people, women appear to have more persistent cognitive effects from smoking marijuana in their teens than do men, and this is a difference we can't explain at this time," says Pletnikov.To find out what particular brain cells might be more responsible for mediating damage from THC, the researchers then genetically engineered their mice so that the mutant DISC1 was turned on only in neurons that send electrical responses and encode memory, or only in astrocytes, the "helper" brain cells that provide support and protection to the neurons.They then exposed both groups of mice to THC in their adolescence as before (three weeks straight, then off for three weeks) and again performed the same tests for recognition memory. They found that only when the mutant DISC1 was turned on in astrocytes did the mice have cognitive problems.Then, to see what the faulty DISC1 did in these astrocytes to worsen the pot-induced cognitive problems, the researchers looked at which genes became more or less active in the brain of the mice with mutant DISC1 after exposure to THC compared with the DISC1 mice without THC exposure or control mice exposed to THC. They identified 56 genes related to inflammation that were specifically turned on in the brain of mutant DISC1 mice exposed to THC.To see if tamping down brain inflammation could prevent the memory problems in the DISC1 mutant mice exposed to THC, the researchers used an anti-inflammatory medication.Adolescent mutant DISC1 mice were given the anti-inflammatory medication NS398 30 minutes before their daily injections with THC. When the mice were older and tested, they didn't have memory problems in the cognitive tests, Pletnikov says."If our results turn out to be applicable to people, they suggest we could develop safer anti-inflammatory treatments to prevent long-term consequences of marijuana use," says Pletnikov. Kamiya adds that being able to identify those who are susceptible and preventing them from partaking in marijuana use is another option for protecting teens' memory.As for future work, Pletnikov's and Kamiya's laboratories are collaborating to expand these studies with other animal models to determine how various genetic vulnerabilities may play a role in marijuana's effects on the developing brain.
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December 13, 2018
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https://www.sciencedaily.com/releases/2018/12/181213142148.htm
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Whether a urinary tract infection recurs may depend on the bacterial strain
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Genetically diverse bacterial strains that cause urinary tract infections differ in their ability to trigger protective immune responses in mice, potentially explaining why these infections frequently recur in many patients, according to a study published December 13 in the open-access journal
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Many patients suffer from highly recurrent urinary tract infections caused by Escherichia coli, which are genetically diverse bacteria. Recurrent episodes are often caused by the same They found that one strain, UTI89, could infect the bladder indefinitely, whereas strain CFT073 was always cleared within eight weeks. After mice had a CFT073 infection and antibiotic treatment, they were protected from a CFT073 challenge infection, but were susceptible to a UTI89 challenge infection. By contrast, mice with a UTI89 infection and antibiotics were susceptible to recurrent urinary tract infections when challenged with either strain. Depleting T cells, immune cells important for developing protection against infection, prevented mice from clearing their CFT073 infections and made them susceptible to recurrent CFT073 urinary tract infections. The findings show that infection with one The authors conclude, "This study shows that some bacteria hide from the immune system to cause urinary tract infections again and again."
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November 30, 2018
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https://www.sciencedaily.com/releases/2018/11/181130120442.htm
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Researchers alleviate Schizophrenia symptoms in new mouse models
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Despite extensive research efforts, schizophrenia remains one of the least understood brain disorders. One promising area of research is in receptors on the surfaces of brain cells that help sense growth factors. But there's been a problem: in previous schizophrenia studies, researchers have genetically manipulated brain cell receptors in very young mice. Schizophrenia usually affects adults.
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In a recent issue of the In the new study, Mei, professor and chair of neurosciences at Case Western Reserve University School of Medicine, led an international team of neuroscientists. The team included Mei's long-time collaborator, Wen-Cheng Xiong, PhD, professor of neurosciences, and first authors Hongsheng Wang and Wenbing Chen, graduate students, all of CWRU. Additional collaborators included researchers at Nanchang University and Guangzhou Medical University in China, and neuroscientists from the Medical College of Georgia at Augusta University.Together, the researchers studied a brain cell receptor -- ErbB4 -- whose level is altered in adults with schizophrenia. ErbB4 helps maintain an inhibitory neurotransmitter in the brain -- GABA -- that prevents brain cells from overreacting and keeps fear and anxiety in check. The researchers have shown previously that ErbB4 mutations change signals inside brain cells that lead to schizophrenic symptoms in mice."When ErbB4 is mutated early on in mice, it impairs brain circuit wiring. It also impairs GABA transmission in adult animals, causing schizophrenic symptoms," said Mei. "But previous models are unable to distinguish whether deficits are from abnormal development in young mice brains, or abnormal transmission developed later on." Mei's new study shows schizophrenic symptoms come from deficits in how brain cells communicate during adulthood, regardless of whether or not they fully developed.To find their answers, Mei's team genetically engineered two new mouse models of schizophrenia. In the first, the researchers treated mice with a chemical that switches "off" the gene encoding ErbB4. "Using inducible knock-out mice, we depleted ErbB4 only in adult animals, and showed that this impairs behavior," said Mei. In mice missing ErbB4 only in adulthood, brain cell development and appearance were normal, but symptoms persisted. The experiment suggested schizophrenic symptoms in adult mice were unrelated to abnormal brain cell development.In the second mouse model, the receptor was missing in mice from the beginning, hampering brain cell development. The researchers used the same genetic switch to turn ErbB4 "on" in adulthood -- in essence, recovering it. "In recovery knock-out mice, ErbB4 is missing during development and thus the mice have crippled brain circuits. Yet, when ErbB4 is restored on a malformed circuit, mice scored better in behavioral tests," said Mei. Even with underdeveloped brain cells, schizophrenic symptoms could be alleviated simply by adding ErbB4.Mei's team found restoring ErbB4 receptors reduced hyperactivity, and normalized fear responses in adult mice. "ErbB4 is a risk factor for schizophrenia," said Mei. "This study shows correcting ErbB4 signaling could be therapeutic in relevant patients."The results in the two mouse models confirm that ErbB4 is critical to how brain cells communicate during adulthood. The nuanced distinction could lead to new therapeutics designed to improve brain cell signaling associated with the ErbB4 receptor. In particular, therapeutics that improve how GABA neurotransmitters regulate brain cell activity."Restoring ErbB4 could be beneficial to patients -- even those with malformed brain circuitry," said Mei. "We are now looking into how restoring ErbB4 improves neurotransmitter signaling inside brain cells, including those relevant to other psychiatric disorders, such as attention deficit hyperactivity disorder and major depression."
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November 28, 2018
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https://www.sciencedaily.com/releases/2018/11/181128082729.htm
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Scientists direct bacteria with expanded genetic code to evolve extreme heat tolerance
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In recent years, scientists have engineered bacteria with expanded genetic codes that produce proteins made from a wider range of molecular building blocks, opening up a promising front in protein engineering.
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Now, Scripps Research scientists have shown that such synthetic bacteria can evolve proteins in the laboratory with enhanced properties using mechanisms that might not be possible with nature's 20 amino acid building blocks.Exposing bacteria with an artificially expanded genetic code to temperatures at which they cannot normally grow, the researchers found that some of the bacteria evolved new heat-resistant proteins that remain stable at temperatures where they would typically inactivate. The researchers reported their findings in the Virtually every organism on earth uses the same 20 amino acids as the building blocks to make proteins -- the large molecules that carry out the majority of cellular functions. Peter Schultz, PhD, the senior author of the This expanded genetic code has been used in the past to rationally design proteins with novel properties for use as tools to study how proteins work in cells and as new precision-engineered drugs for cancer. The researchers now asked whether synthetic bacteria with expanded genetic codes have an evolutionary advantage over those that are limited to 20 building blocks -- is a 21 amino acid code better than a 20 amino acid code from an evolutionary fitness perspective?"Ever since we first expanded the range of amino acids that can be incorporated in proteins, much work has gone into using these systems to engineer molecules with new or enhanced properties," says Schultz. "Here, we've shown that combining an expanded genetic code with a laboratory evolution one can create proteins with enhanced properties that may not be readily achievable with nature's more limited set."The scientists started by tweaking the genome of At this point, they let natural selection -- the central mechanism of evolution -- work its magic. By heating the bacteria to 44 degrees Celsius -- a temperature at which normal metA protein cannot function, and as a consequence, bacteria cannot grow -- the scientists put selective pressure on the bacteria population. As expected, some of the mutant bacteria were able to survive beyond their typical temperature ceiling, thanks to possessing a mutant metA that was more heat stable -- all other bacteria died.In this way, the researchers were able to drive the bacteria to evolve a mutant metA enzyme that could withstand temperatures 21 degrees higher than normal, nearly twice the thermal stability increase that people typically achieve when restricted to mutations limited to the common 20 amino acid building blocks.The researchers then identified the specific genetic sequence change that resulted in the mutant metA and found it was due to the unique chemical properties of one of their noncanonical amino acids that laboratory evolution exploited in a clever way to stabilize the protein."It's striking how making such a small mutation with a new amino acid not present in nature leads to such a significant improvement in the physical properties of the protein," says Schultz."This experiment raises the question of whether a 20 amino acid code is the optimal genetic code -- if we discover life forms with expanded codes will they have an evolutionary advantage, and what would we be like if God had worked on the seventh day and added a few more amino acids to the code?"In addition to Schultz, authors of the study, Enhancing Protein Stability with Genetically Encoded Noncanonical Amino Acids, include Jack C. Li, Tao Liu, Yan Wang and Angad P. Mehta, of Scripps Research. The study was supported by the National Institutes of Health (grant R01 GM062159).
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November 27, 2018
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https://www.sciencedaily.com/releases/2018/11/181127131612.htm
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First calf born following IVF embryo breakthrough
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The approach, called Karyomapping, was originally designed to detect and screen for single gene and chromosome disorders simultaneously in human IVF embryos.
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Now the application of the same technique to cattle IVF -- involving screening at the embryo stage rather than when a calf is born -- will allow decisions on best quality genetic stock to be made earlier.The latest research, led by Professor Darren Griffin of the University's School of Biosciences, will allow for better quality genetics to be introduced more rapidly into the breeding herd.Moving genetically screened embryos around the country, and around the world, rather than live animals, is also more biosecure, environmentally friendly and means that they can be delivered to breeding farms in a more efficient manner.Professor Griffin said: 'In-vitro produced embryos are used widely in the cattle breeding industry but this is the first time they have undergone a whole genomic screen beforehand. We have used Karyomapping to screen for genetic merit, as well as the incidence of chromosome disorders, which could significantly reduce the chances of the embryos developing into live-born calves.'The researchers report the birth of the calves to be born following use of the technique, including the first named Crossfell Cinder Candy, born on a farm near Penrith.
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November 27, 2018
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https://www.sciencedaily.com/releases/2018/11/181127092517.htm
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Bee gene study sheds light on risks to hives
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Efforts to protect the UK's native honey bees could be helped by research that maps their entire genetic make-up.
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Experts also analysed the genetic profile of bacteria and other organisms that live inside bees, to shed new light on emerging diseases that threaten bee colonies.Researchers say their findings could help to safeguard native bee populations from the effects of infectious diseases through improved health monitoring.Bees play a vital role in helping to pollinate crops and wild plants, so minimising risks to them is crucial.A team led by the University of Edinburgh analysed the entire genetic makeup of bee colonies from across the UK and compared them with recently imported bees.They found that bees from some hives in Scotland were genetically very similar to the UK's native dark honey bee, even though southern European strains have been imported for many yearsThe researchers from the University's Roslin Institute say this is good news as native bees were thought to be endangered in the UK. They suggest this could mean that native bees survive better in cooler climates than their relatives from southern Europe.The team also analysed the genetic makeup of bacteria and other organisms that live inside bees -- the so-called metagenome.The findings uncovered organisms that had not been seen before in honey bees and that may cause disease. Hives that are infected with these organisms may also be more susceptible to other infections.The research is published in The Roslin Institute receives strategic funding from the Biotechnology and Biological Sciences Research Council.Dr Tim Regan, a Postdoctoral Research Fellow at the University of Edinburgh's Roslin Institute, said: "We have created a platform that could revolutionise how we monitor threats to honey bees and maintain their health. The decreasing cost of DNA sequencing could potentially allow this type of analysis to become routine."
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November 26, 2018
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https://www.sciencedaily.com/releases/2018/11/181126123317.htm
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New biocontainment strategy controls spread of escaped GMOs
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Hiroshima University (HU) researchers successfully developed a biocontainment strategy for genetically modified organisms, or GMOs. Their new method prevents genetically modified cyanobacteria from surviving outside of their test environment, enabling ways to more safely research the effects of GMOs. Their results were published in
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The applications of bioengineered microbes have appeared in a number of fields, including agriculture and energy production. Engineered microalgae, for example, can help clean up oil refinery wastewater and work as a source of biofuel. However, like many other GMOs, the safety of engineered microalgae is uncertain."Engineered microbes could dominate some environment or attack an organism indigenous to it, and that could negatively affect biodiversity," Ryuichi Hirota said, who is the primary author of this paper. Hirota is an Associate Professor in the Graduate School of Advanced Sciences of Matter at HU. "Additionally, microalgae is usually cultivated in ponds and other bodies of water open to the environment. To overcome that risk, one strategy is to apply a biocontainment system in microalgae."Biocontainment strategies seek to stop outgrowth of GMOs in a specific area, like outside of the lab environment. Hirota was particularly interested in "a passive strategy," the aim of which is to alter a microbe's nutrient requirements. By engineering a microbe to depend on a certain nutrient that does not exist outside of its home environment, then it will not survive if it escapes this environment.In his case, the microbe is microalgae, and the nutrient is phosphite.At the core of phosphite is phosphorus, a crucial element in living things. Phosphorus also makes up a different molecule called phosphate, which makes up the backbone of DNA and the intracellular energy currency molecule ATP. Phosphate is abundant in the natural world. Phosphite, on another hand, is not.Thanks to an enzyme called phosphite dehydrogenase, a small number of microbes can metabolize phosphite into phosphate. While organisms require phosphorus, many cannot use phosphite due to lacking this enzyme. Hirota took advantage of this naturally occurring process to create a biocontainment process for In this study, the group applied this system in microalgae, a kind of cyanobacteria that lives in water. Like However, "escaped mutants are always a possibility," Hirota said. With that, they tested the effectiveness of their biocontainment strategy by measuring how many strains of microalgae adapted to rely on phosphite. Over the course of three weeks, the team observed zero colonies. The escape frequency was at least three magnitudes lower than NIH laboratory standards, which is less than one mutant cell per 100 million normal cells, and is comparable to other cyanobacteria containment strategies currently in use.The next step in evaluating this strain of microalgae will go beyond the Petri dish. "I would like to test it in an open but closed model ecosystem," Hirota said. That is to say, test the strain in an artificial pond, but still within a controlled setting."Using GMOs is a balance of risk and benefit," he concluded. "They have potential, but at the same time, they have a health risk. If we don't have any techniques that allow us to research them more safely, we do not have a choice. We need to develop such biosafety systems so we can study GMOs more responsibly."
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November 15, 2018
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https://www.sciencedaily.com/releases/2018/11/181115144910.htm
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Solar panels for yeast cell biofactories
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Genetically engineered microbes such as bacteria and yeasts have long been used as living factories to produce drugs and fine chemicals. More recently, researchers have started to combine bacteria with semiconductor technology that, similar to solar panels on the roof of a house, harvests energy from light and, when coupled to the microbes' surface, can boost their biosynthetic potential.
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The first "biological-inorganic hybrid systems" (biohybrids) mostly focused on the fixation of atmospheric carbon dioxide and the production of alternative energies, and although promising, they also revealed key challenges. For example, semiconductors, which are made from toxic metals, thus far are assembled directly on bacterial cells and often harm them in the process. In addition, the initial focus on carbon-fixing microbes has limited the range of products to relatively simple molecules; if biohybrids could be created based on microorganisms equipped with more complex metabolisms, it would open new paths for the production of a much larger range of chemicals useful for many applications.Now, in a study in "While our strategy conceptually builds on earlier bacterial biohybrid systems that were engineered by our collaborator Daniel Nocera and others, we expanded the concept to yeast -- an organism that is already an industrial workhorse and is genetically easy to manipulate -- with a modular semiconductor component that provides biochemical energy to yeast's metabolic machinery without being toxic," said Joshi, Ph.D., who is a Core Faculty member at the Wyss Institute and Associate Professor at SEAS. Co-author Nocera is the Patterson Rockwood Professor of Energy at Harvard University. As a result of the combined manipulations, yeasts' ability to produce shikimic acid, an important precursor of the anti-viral drug Tamiflu, several other medicines, nutraceuticals, and fine chemicals, was significantly enhanced.The baker's yeast "In principle, the increased 'carbon flux' towards shikimic acid should lead to higher product levels, but in normal yeast cells, the alternative pathway that we disrupted to increase yields, importantly, also provides the energy needed to fuel the final step of shikimic acid production," said co-first author Miguel Suástegui, Ph.D., a chemical engineer and former Postdoctoral Fellow in Joshi's team and now Scientist at Joyn Bio LLC. To boost the more carbon-effective but energy-depleted engineered shikimic acid pathway, "we hypothesized that we could generate the relevant energy-carrying molecule NADPH instead in a biohybrid approach with light-harvesting semiconductors."Toward this goal, Suástegui collaborated with Junling Guo, Ph.D., the study's other co-corresponding and co-first author and presently a Postdoctoral Fellow with experience in chemistry and materials science in Joshi's lab. They designed a strategy that uses indium phosphide as a semiconductor material. "To make the semiconductor component truly modular and non-toxic, we coated indium phosphide nanoparticles with a natural polyphenol-based "glue," which allowed us to attach them to the surface of yeast cells while at the same time insulating the cells from the metal's toxicity," said Guo.When tethered to the cell surface and illuminated, the semiconductor nanoparticles harvest electrons (energy) from light and hand them over to the yeast cells, which shuttle them across their cell walls into their cytoplasm. There the electrons elevate the levels of NADPH molecules, which now can fuel shikimic acid biosynthesis. "The yeast biohybrid cells, when kept in the dark, mostly produced simpler organic molecules such as glycerol and ethanol; but when exposed to light, they readily switched into shikimic acid production mode with an 11-fold increase in product levels, showing us that the energy transfer from light into the cell works very efficiently," said Joshi."This scalable approach creates an entirely new design space for future biohybrid technologies. In future efforts, the nature of semiconductors and the type of genetically engineered yeast cells can be varied in a plug-and-play fashion to expand the type of manufacturing processes and range of bioproducts," said Guo."The creation of light-harvesting, living cellular devices could fundamentally change the way we interact with our natural environment and allow us to be more creative and effective in the design and production of energy, medicines and chemical commodities," said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at SEAS.
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November 13, 2018
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https://www.sciencedaily.com/releases/2018/11/181113155150.htm
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Synthetic DNA-delivered antibodies protect against Ebola in preclinical studies
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Scientists at The Wistar Institute and collaborators have successfully engineered novel DNA-encoded monoclonal antibodies (DMAbs) targeting Zaire Ebolavirus that were effective in preclinical models. Study results, published online in
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Ebola virus infection causes a devastating disease, known as Ebola virus disease, for which no licensed vaccine or treatment are available. The 2014-2016 Zaire Ebola virus epidemic in West Africa was the most severe reported to date, with more than 28,600 cases and 11,325 deaths according to the Center for Disease Control. A new outbreak is ongoing in the Democratic Republic of Congo, with a death toll of more than 200 people since August. One of the experimental avenues scientists are pursuing is evaluating the safety and efficacy of monoclonal antibodies isolated from survivors as promising candidates for further development as therapeutics against Ebola virus infection. However, this approach requires high doses and repeated administration of recombinant monoclonal antibodies that are complex and expensive to manufacture, so meeting the global demand while keeping the cost affordable is challenging."Our studies show deployment of a novel platform that rapidly combines aspects of monoclonal antibody discovery and development technology with the revolutionary properties of synthetic DNA technology," said lead researcher David B. Weiner, Ph.D., executive vice president and director of Wistar's Vaccine & Immunotherapy Center, and W.W. Smith Charitable Trust Professor in Cancer Research.The team designed and enhanced optimized DMAbs that, when injected locally, provide the genetic blueprint for the body to make functional and protective Ebola virus-specific antibodies, circumventing multiple steps in the antibody development and manufacturing process. Dozens of DMAbs were tested in mice and the best-performing ones were selected for further studies. These proved to be highly effective for providing complete protection from disease in challenge studies."Due to intrinsic biochemical properties, some monoclonal antibodies might be difficult and slow to develop or even impossible to manufacture, falling out of the development process and causing loss of potentially effective molecules," added Weiner. "The DMAb platform allows us to collect protective antibodies from protected persons and engineer and compare them rapidly and then deliver them in vivo to protect against infectious challenge. Such an approach could be important during an outbreak, when we need to design, evaluate and deliver life-saving therapeutics in a time-sensitive manner.""We started with antibodies isolated from survivors and compared the activity of anti-Ebola virus DMAbs and recombinant monoclonal antibodies over time," said Ami Patel, Ph.D., first author on the study and associate staff scientist in the Wistar Vaccine and Immunotherapy Center. "We showed that in vivo expression of DMAbs supports extended protection over traditional antibody approaches."The researchers also looked at how DMAbs physically interact with their Ebola virus targets, called epitopes, and confirmed that DMAbs bind to identical epitopes as the corresponding recombinant monoclonal antibodies made in traditional bioprocess facilities.The Weiner Laboratory is also developing an anti-Ebola virus DNA vaccine. Preclinical results from this efforts were published recently in the
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November 5, 2018
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https://www.sciencedaily.com/releases/2018/11/181105122514.htm
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Small genetic differences turn plants into better teams
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The ongoing worldwide loss of biological diversity is one of the most pressing challenges humankind currently faces. Biodiversity is vital to humans not least because it supports ecosystem services such as the provision of clean water and the production of biomass and food. Many experiments have shown that diverse communities of organisms function better in this regard than monocultures. "In mixed communities plants engage in a kind of division of labor that increases efficiency and improves the functioning of the community as a whole," explains Pascal Niklaus from the Department of Evolutionary Biology and Environmental Studies of the University of Zurich.
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Nevertheless, modern agricultural practice mainly relies on plant varieties that are genetically uniform, since they make it easier to grow and process crops. The benefits of diverse communities therefore remain untapped, also because the underlying mechanisms are not yet fully understood. "Despite intensive research, we currently don't know which properties make plants good players in such mixed teams," says Samuel Wüst, main author of the study.The two researchers addressed this question by combining modern genetic and ecological approaches. As a test system, they focused on common wallcress (Using statistical analyses, the researchers then related the yield gain in mixed communities to the genetic makeup of the crosses. The genetic map they obtained in this way enabled them to identify the parts of the genome that made the combination of plants good mixed teams. They found that even the smallest genetic differences between plants were enough to increase their combined yield."We were very surprised that complex and poorly understood properties such as the suitability to form a well-performing mixture had such a simple genetic cause," says Samuel Wüst. He thinks that their method may help to breed plants that are good team players and thus yield more crops. "Our insights open up completely new avenues in agriculture," adds Wüst.
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Genetically Modified
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October 29, 2018
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https://www.sciencedaily.com/releases/2018/10/181029164644.htm
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Synthetic microorganisms allow scientists to study ancient evolutionary mysteries
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Scientists at Scripps Research and their collaborators have created microorganisms that may recapitulate key features of organisms thought to have lived billions of years ago, allowing them to explore questions about how life evolved from inanimate molecules to single-celled organisms to the complex, multicellular lifeforms we see today.
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By studying one of these engineered organisms-a bacterium whose genome consists of both ribonucleic acid (RNA) and deoxyribonucleic acid (DNA)-the scientists hope to shed light on the early evolution of genetic material, including the theorized transition from a world where most life relied solely on the genetic molecule RNA to one where DNA serves as the primary storehouse of genetic information.Using a second engineered organism, a genetically modified yeast containing an endosymbiotic bacterium, they hope to better understand the origins of cellular power plants called mitochondria. Mitochondria provide essential energy for the cells of eukaryotes, a broad group of organisms-including humans-that possesses complex, nucleus-containing cells.The researchers report engineering the microbes in two papers, one published October 29, 2018 in the "These engineered organisms will allow us to probe two key theories about major milestones in the evolution of living organisms-the transition from the RNA world to the DNA world and the transition from prokaryotes to eukaryotes with mitochondria," says Peter Schultz, PhD, senior author on the papers and president of Scripps Research. "Access to readily manipulated laboratory models enables us to seek answers to questions about early evolution that were previously intractable."The origins of life on Earth have been a human fascination for millennia. Scientists have traced the arc of life back several billion years and concluded that the simplest forms of life emerged from Earth's primordial chemical soup and subsequently evolved over the eons into organisms of greater and greater complexity. A monumental leap came with the emergence of DNA, a molecule that stores all of the information required to replicate life and directs cellular machinery to do its bidding primarily by generating RNA, which in turn directs the synthesis of proteins, the molecular workhorses in cells.In the 1960s, Carl Woese and Leslie Orgel, along with DNA pioneer Francis Crick, proposed that before DNA, organisms relied on RNA to carry genetic information, a molecule similar to but far less stable than DNA, that can also catalyze chemical reactions like proteins. "In science class, students learn that DNA leads to RNA which in turn leads to proteins-that's a central dogma of biology-but the RNA world hypothesis turns that on its head," says Angad Mehta, PhD, first author of the new papers and a postdoctoral research associate at Scripps Research. "For the RNA world hypothesis to be true, you have to somehow get from RNA to a DNA genome, yet how that might have happened is still a very big question among scientists."One possibility is that the transition proceeded through a kind of microbial missing link, a replicating organism that stored genetic information as RNA. For the JACS study, the Scripps Research-led team created Escherichia coli bacteria that partially build their DNA with ribonucleotides, the molecular building blocks typically used to build RNA. These engineered genomes contained up to 50 percent RNA, thus simultaneously representing a new type of synthetic organism and possibly a throwback to billions of years ago.Mehta cautions that their work so far has focused on characterizing this chimeric RNA-DNA genome and its effect on bacterial growth and replication but hasn't explicitly explored questions about the transition from the RNA world to the DNA world. But, he says, the fact that For instance, one question is whether the presence of RNA leads to rapid genetic drift-large changes in gene sequence in a population over time. Scientists theorize that massive genetic drift occurred quickly during early evolution, and the presence in the genome of RNA could help explain how genetic change occurred so quickly.In the paper published in Mitochondria are widely thought to have evolved from ordinary bacteria that were captured by larger, single-celled organisms. They carry out several key functions in cells. Most importantly, they serve as oxygen reactors, using OMitochondria have a double-membrane structure like that of some bacteria, and-again, like bacteria-contain their own DNA. Analyses of the mitochondrial genome suggest that it shares an ancient ancestor with modern Rickettsia bacteria, which can live within the cells of their hosts and cause disease. Stronger support for the bacterial origin of mitochondria theory would come from experiments showing that independent bacteria could indeed be transformed, in an evolution-like progression, into mitochondria-like symbionts. To that end, the Scripps Research scientists engineered The researchers started by modifying The team found that some of the engineered bacteria, after being modified with surface proteins to protect them from being destroyed in the yeast, lived and proliferated in harmony with their hosts for more than 40 generations and appeared to be viable indefinitely. "The modified bacteria seem to accumulate new mutations within the yeast to better adapt to their new surroundings," says Schultz.With this system established, the team will try to evolve the The Scripps Research team rounded out the study with further gene-subtraction experiments, and the results were promising: they found they could eliminate not just the "We are now well on our way to showing that we can delete the genes for making all 20 amino acids, which comprise a significant part of the The researchers also hope to use similar endosymbiont-host systems to investigate other important episodes in evolution, such as the origin of chloroplasts, light-absorbing organelles that have a mitochondria-like role in supplying energy to plants.
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October 29, 2018
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https://www.sciencedaily.com/releases/2018/10/181029150947.htm
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Genetic search reveals key to resistance in global cotton pest
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In the most recent battle in the unending war between farmers and bugs, the bugs are biting back by adapting to crops genetically engineered to kill them.
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A new study published in the Cotton, corn and soybean have been genetically engineered to produce pest-killing proteins from the widespread soil bacterium Bacillus thuringiensis, or Bt. Non-toxic to people and wildlife including bees, these environmentally friendly Bt proteins have been used in sprays by organic growers for more than 50 years and in engineered Bt crops planted by millions of farmers worldwide on a cumulative total of more than two billion acres since 1996.Entomologists at the University of Arizona, the University of Tennessee and the Nanjing Agricultural University in China collaborated in the three-part study. Their goals were to pinpoint the mutation conferring Bt resistance in bollworms, precisely edit one bollworm gene to prove this mutation causes resistance and discover how the resistance is spreading through cotton fields in China."It's a remarkable detective story," said Bruce Tabashnik, Regents' Professor in the UA Department of Entomology and co-author of the study. "Without the latest advances in genetic technology, it would not have been possible to find the single DNA base pair change causing resistance among the hundreds of millions of base pairs in the bollworm's genome."For years, scientists have known that insects can evolve resistance to Bt proteins, just as they have to conventional insecticides. However, Bt resistance is inherited recessively in nearly all previously studied cases. This means insects must have two copies of the resistance gene -- one from each parent -- to enable them to feed and survive on the Bt crop.To combat resistance, farmers plant refuges of non-Bt crops, where susceptible insects can thrive. The idea is the rare resistant insects will mate with the more abundant susceptible insects from refuges, producing offspring that harbor only one copy of the resistance gene. With recessively inherited resistance, such offspring do not survive on the Bt crop.Though refuges do not stop evolution of resistance altogether, they can delay it substantially -- particularly when resistance is recessive.But in China, the paper reports, dominant bollworm resistance to Bt is on the rise. Only one copy of a dominant mutation makes a bollworm resistant.Because the genetic basis of dominant Bt resistance was previously unknown, the researchers had to scrutinize the bollworm's entire genome to find the culprit. By comparing the DNA of resistant and susceptible bollworms, they narrowed the search from 17,000 genes to a region of just 21 genes associated with resistance."But only 17 of those genes code for proteins that are produced by the caterpillars," Tabashnik said, explaining that only the bollworm caterpillars feed on cotton and can be killed by Bt proteins."In comparing the sequences of those 17 genes between the strains, there was only one consistent difference," Tabashnik said. "There was one position where all of the resistant bollworms had one DNA base pair and all of the susceptible bollworms had a different DNA base pair."This pivotal base pair is in a newly identified gene named HaTSPAN1, which codes for a tetraspanin -- a protein containing four segments that span cell membranes. Although the normal function of HaTSPAN1 is not known, many other tetraspanins are important in cell-to-cell communication. Despite nearly 30,000 previous studies of either Bt or tetraspanins, the new study is the first to find a strong connection between them.With the mutant base pair identified, the second challenge was to determine if this single mutation causes resistance. To find out, the research team used the gene-editing tool CRISPR to precisely alter only the HaTSPAN1 gene. When the gene was disrupted in resistant bollworms, they became completely susceptible to Bt. Conversely, when the mutation was inserted in the DNA of susceptible bollworms, they became resistant -- proving this single base pair change alone can cause resistance.The final step was to test the hypothesis that this mutation contributes to resistance to Bt cotton in the field. By screening for the mutation in the DNA of thousands of preserved bollworm moths collected between 2006 and 2016, the researchers found the frequency of the mutation increased by a factor of 100, from 1 in 1,000 to 1 in 10.The resistant bollworms are not yet numerous enough to noticeably decrease cotton production in China, but the dominant gene is spreading faster than other resistance genes. Tabashnik's analysis predicts that if the current trend continues, half of northern China's cotton bollworms will have resistance conferred by this mutation within five years."If things continue on the same trajectory, this is the mutation that is going to cause problems for the farmers in the field," said Tabashnik.It is early enough, however, for farmers in China to change their tactics and ward off Bt resistance. The paper mentions they could switch from cotton that produces only one Bt protein to the types of cotton grown in the United States and Australia, which produce two or three distinct Bt proteins. Tabashnik hopes the new research will spur enhanced sustainability for farmers."It gives them the information to make constructive, proactive decisions before it's too late," Tabashnik said.By sampling pest populations from year to year, farmers and researchers may be able to learn which methods are most effective for thwarting resistance.Understanding bollworm resistance has global implications because it occurs in over 150 countries and now threatens to invade the United States."It will be interesting to screen for this mutation in cotton bollworm from Australia, India, and Brazil," said Yidong Wu, a professor of entomology at Nanjing Agricultural University who led the research in China.Of course, the technology to scan genomes is not limited to one species of crop pest."The data shows that genomic scans will be helpful in monitoring resistance evolution not only for Bt, but for insecticides in general," said Fred Gould, who was not involved in the study but is a professor of entomology at North Carolina State University and member of the National Academy of Sciences.
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October 25, 2018
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https://www.sciencedaily.com/releases/2018/10/181025142037.htm
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Evolution does repeat itself after all: How evolution lets stripes come and go
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A team of evolutionary biologists from the University of Konstanz, headed by Prof. Dr. Axel Meyer, discovers the genetic basis for the repeated evolution of colour patterns. The findings about the stripes of the especially diverse species of East-African cichlid fishes explain how evolution can repeat itself at record speed. The study is published in
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Why does evolution repeat itself? What happens genetically during these repetitions? Do the same or other genes and mechanisms produce organisms that look similar? Professor Axel Meyer and his team from Konstanz University have come closer to answering this question that is as old as it is important. The answer is quite astonishing. They studied a special colour pattern that is omnipresent among all kinds of animals: horizontal stripes. The researchers were able to identify the basis of the repeated evolution of these stripes with modern methods in genomics and molecular biology and verified them with a CRISPR-Cas mutant fish that added a stripe.More than 1200 types of colourful cichlid can be found in the large African lakes Malawi, Victoria and Tanganjika. Not only are they very diverse in colours, they also have numerous colour patterns such as horizontal or vertical stripes. "But that's not all" explains Axel Meyer, "cichlids are prime examples of evolution. They are extremely diverse in terms of social behaviour, body shape, colour pattern and many other biological aspects, but at the same time certain features repeatedly evolved independently in the different lakes." This principle of repeated evolution -- biologists term it convergent evolution -- makes cichlids the perfect target to study the genetic basis of this phenomenon. If similar colours and body shapes have emerged in several evolutionary lines independently from each other this means that evolution reacted to similar environmental conditions in the same way. The question now is: When evolution repeats itself, how does this work genetically?Which gene and which genetic mechanism are responsible for the cichlids' stripes to come and go has now been reconstructed in the laboratory through genome analyses, breeding and experiments, including CRISPR-Cas as "gene scissors." Dr Claudius Kratochwil, early career researcher in Professor Meyers team and first author of the study in The latest findings on this genetic mechanism, the activation or deactivation of stripes by the "stripes gene," were published in the current issue of
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October 16, 2018
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https://www.sciencedaily.com/releases/2018/10/181016132012.htm
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Public opinion on GMOs might impact similar technologies in stores
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If an individual is skeptical about the safety of genetically modified foods, chances are they're wary of nanotechnology, too.
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Researchers at the University of Missouri have found that an individual's perception of genetically modified organisms might impact their judgments about whether or not nanotechnology-enabled products should be labeled in stores. GMOs are foods and organisms that have been genetically modified to alter their characteristics to achieve a specific outcome. For example, a tomato might be altered to increase its hardiness against pests. Nanotechnology involves manipulating a material's atoms and molecules at the nanoscale to improve their function, such as making a t-shirt's fibers more resistant to sunlight, or altering a golf club's surface to help it hit balls harder."Most people do not have the time nor resources to keep up with every scientific advancement, and so they might rely on past experiences or judgments to make decisions about new technologies," said Heather Akin, an assistant professor in the Missouri School of Journalism. "For example, individuals have indicated their support for labeling GMO products if they believe they pose a risk to their health or the environment. So we wanted to know if people's opinions on GMOs influence how they feel about nanotechnology."Currently, the U.S. does not require labeling the more than 1,800 nano products on the market. Because most of the public is unaware of nanotechnology, people might associate it with GMOs, another complex topic that involves manipulating materials at the molecular level.Akin surveyed nearly 3,000 adults in the U.S. to collect their views on GMOs, nanotechnology and labeling products available for purchase. She found that those who believe GMOs are beneficial are less likely to support labeling of nano products, even if they don't believe nanotechnology has many benefits. Akin also found that those who are less trusting of scientific authorities are more inclined to favor labeling nano products if they do not think GMOs are beneficial to society. The findings could help businesses and regulating agencies understand how consumers view emerging technologies and better inform shoppers' purchasing decisions."If consumers are grouping together these two different technologies, they could potentially be basing their attitudes on nanotechnology on past beliefs, instead of the facts," Akin said. "That means they could be limiting their choices and missing out on effective products."
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October 11, 2018
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https://www.sciencedaily.com/releases/2018/10/181011143115.htm
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Mouse pups with same-sex parents born in China using stem cells and gene editing
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Researchers at the Chinese Academy of Sciences were able to produce healthy mice with two mothers that went on to have normal offspring of their own. Mice from two dads were also born but only survived for a couple of days. The work, presented October 11 in the journal
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"We were interested in the question of why mammals can only undergo sexual reproduction. We have made several findings in the past by combining reproduction and regeneration, so we tried to find out whether more normal mice with two female parents, or even mice with two male parents, could be produced using haploid embryonic stem cells with gene deletions," says co-senior author Qi Zhou.While some reptiles, amphibians, and fish can reproduce with one parent of the same sex, it's challenging for mammals to do the same even with the help of fertilization technology. In mammals, because certain maternal or paternal genes are shut off during germline development by a mechanism called genomic imprinting, offspring that don't receive genetic material from both a mother and a father might experience developmental abnormalities or might not be viable. By deleting these imprinted genes from immature eggs, researchers have produced bimaternal mice -- mice with two mothers -- in the past. "However, the generated mice still showed defective features, and the method itself is very impractical and hard to use," says Zhou.To produce their healthy bimaternal mice, Zhou, co-senior author Baoyang Hu, co-senior author Wei Li, and their colleagues used haploid embryonic stem cells (ESCs), which contain half the normal number of chromosomes and DNA from only one parent and which the researchers believe were the key to their success. The researchers created the mice with two mothers by deleting three imprinting regions of the genome from haploid ESCs containing a female parent's DNA and injected them into eggs from another female mouse. They produced 29 live mice from 210 embryos. The mice were normal, lived to adulthood, and had babies of their own.One advantage of using haploid ESCs is that even before the problematic genes are knocked out, they contain less of the imprinting programming that ultimately causes maternal- or paternal-specific genes to be expressed. "We found in this study that haploid ESCs were more similar to primordial germ cells, the precursors of eggs and sperm. The genomic imprinting that's found in gametes was 'erased,'" says Hu.Twelve live, full-term mice with two genetic fathers were produced using a similar but more complicated procedure. Haploid ESCs containing only a male parent's DNA were modified to delete seven key imprinted regions. The edited haploid ESCs were then injected -- along with sperm from another male mouse -- into an egg cell that had its nucleus, and therefore its female genetic material, removed. This created an embryo containing only genomic DNA from the two male parents. These embryos were transferred along with placental material to surrogate mothers, who carried them to term.These pups survived 48 hours after birth, but the researchers are planning to improve the process so that the bipaternal mice live to adulthood. Similar results were achieved in 2011 but using a method that relied on a female intermediary produced from the first father's stem cells to mate with the second father. That method sidestepped the problem of genomic imprinting but presents ethical and practical hurdles if this technology were to ever be considered for humans.Li notes that there are still obstacles to using these methods in other mammals, including the need to identify problematic imprinted genes that are unique to each species and concerns for the offspring that don't survive or that experience severe abnormalities. They do hope, however, to explore these techniques in other research animals in the future."This research shows us what's possible," he says. "We saw that the defects in bimaternal mice can be eliminated and that bipaternal reproduction barriers in mammals can also be crossed through imprinting modification. We also revealed some of the most important imprinted regions that hinder the development of mice with same sex parents, which are also interesting for studying genomic imprinting and animal cloning."
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October 11, 2018
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https://www.sciencedaily.com/releases/2018/10/181011143101.htm
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New route of acquiring antibiotic resistance in bacteria is the most potent one to date
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Bacteriophages (or phages) are viruses that infect and parasitize bacteria. These phages can transfer DNA from one bacterium to another, through a process known as genetic transduction. This is thought to be the major means by which bacteria evolve and acquire the antibiotic resistance and virulence factors that accelerate the emergence of new and progressively more pathogenic strains. Up to now, two mechanisms of genetic transduction were known: generalized and specialized transduction. For over 60 years, since their discovery by American scientist and Nobel laureate Joshua Lederberg, these two mechanisms have stood as the only mechanisms of genetic transduction.
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In a paper published online in the journal When a phage infects a bacterial cell, it normally reproduces in one of two ways: 1) the lytic cycle, in which the phage reproduces and lyses the cell, resulting in the release of new phage particles; or 2) the lysogenic cycle, in which the phage DNA incorporates into the host genome and replicates together with the host genome. In (2), certain stimuli can provoke the phage DNA to cut itself out of the host genome (excision), assemble with proteins into new phage particles (packaging), undergo maturation and lyse the host cells. The released phages from both (1) and (2) can then infect other bacteria and transfer their DNA, which includes DNA from the host cell.In contrast, the researchers, led by Assistant Professor John Chen of NUS Medicine, found that lateral transduction occurs when phages delay excision to late in their life cycle. Instead, the phages initiate DNA replication while they are still part of the host genome, resulting in multiple integrated phage genomes. DNA packaging can then initiate on some genomes, resulting in the packaging and transfer of chromosomal DNA to other bacteria, while other phage genomes excise and lead to normal phage maturation.In Assistant Professor Chen's words, "lateral transduction elevates the concept of mobile genetic elements well beyond that of defined DNA elements, by transforming sections of the genome into hypermobile platforms that are capable of transferring any genetic element within their boundaries at incredibly high frequencies."The discovery of this highly efficient mode of gene transfer could help to explain the rapid evolution of bacteria that occurs, for example, in the development of multi-drug resistant strains.Putting the discovery in context, Assistant Professor Chen observed that "phages are by far the most abundant biological entities on the planet, and the importance of genetic transduction as one of the principal drivers of microbial evolution has never been more apparent than with the discovery of lateral transduction."
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October 10, 2018
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https://www.sciencedaily.com/releases/2018/10/181010132338.htm
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Creating custom brains from the ground up
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Scientists studying how genetics impact brain disease have long sought a better experimental model. Cultures of genetically-modified cell lines can reveal some clues to how certain genes influence the development of psychiatric disorders and brain cancers. But such models cannot offer the true-to-form look at brain function that can be provided by genetically-modified mice.
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Even then, carefully breeding mice to study how genes impact the brain has several drawbacks. The breeding cycles are lengthy and costly, and the desired gene specificity can only be verified -- but not guaranteed -- when mouse pups are born.In today's This "forebrain substitution" results in fully functioning mouse pups that have tightly controlled genetics, allowing scientists to study how specific genes influence disorders of the brain with a greater degree of control."We think of this strategy as a completely new platform for neurobiologists to study many aspects of the brain, from basic knowledge of which genes control brain development to potentially finding new gene therapies for brain cancers and psychiatric disorders," says Fred Alt, PhD, a co-senior author on the new paper and the director of the Boston Children's Program in Cellular and Molecular Medicine."Mice with embryonic-stem-cell-derived brain regions are indistinguishable from normal mice in memory and learning tasks," notes Bjoern Schwer, MD, PhD, a former trainee in Alt's lab who is now an assistant professor at UCSF and co-senior author on the paper.Alt and his team, including Schwer, are also publishing a detailed set of instructions so that scientists around the world can rapidly implement the technique in their own neurobiology laboratories.A particular goal of the Alt lab in developing this technique is to use it as a platform to study a set of genes that they recently discovered are highly susceptible to breaking in mouse brain progenitor cells. They want determine the frequency and mechanisms by which these genes may break, and determine whether this breakage process contributes to neuropsychiatric diseases and brain cancers.What's more, Alt and Schwer believe the technique could be implemented to aid personalized medicine. By creating custom mouse brain models, physician-scientists could mimic the unique genetic profile of undiagnosed patients with rare brain diseases and disorders.
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October 10, 2018
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https://www.sciencedaily.com/releases/2018/10/181010111946.htm
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Blue roses could be coming soon to a garden near you
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For centuries, gardeners have attempted to breed blue roses with no success. But now, thanks to modern biotechnology, the elusive blue rose may finally be attainable. Researchers have found a way to express pigment-producing enzymes from bacteria in the petals of a white rose, tinting the flowers blue. They report their results in
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Although blue roses do not exist in nature, florists can produce blue-hued flowers by placing cut roses in dye. Also, in a painstaking 20-year effort, biotechnologists made a "blue rose" through a combination of genetic engineering and selective breeding. However, the rose is more mauve-colored than blue. Yihua Chen, Yan Zhang and colleagues wanted to develop a simple process that could produce a true-blue rose.For this purpose, the researchers chose two bacterial enzymes that together can convert L-glutamine, a common constituent of rose petals, into the blue pigment indigoidine. The team engineered a strain of
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Genetically Modified
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October 9, 2018
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https://www.sciencedaily.com/releases/2018/10/181009102511.htm
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A step towards biological warfare with insects?
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Owing to present-day armed conflicts, the general public is well aware of the terrifying effects of chemical weapons. Meanwhile, the effects of biological weapons have largely disappeared from public awareness.
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A project funded by a research agency of the US Department of Defense is now giving rise to concerns about being possibly misused for the purpose of biological warfare. The programme called 'Insect Allies' intends for insects to be used for dispersing genetically modified viruses to agricultural plants in fields. These viruses would be engineered so they can alter the chromosomes of plants through 'genome editing'. This would allow for genetic modifications to be implemented quickly and at a large scale on crops that are already growing in fields, such as corn. In the journal It is argued by the programs funders, that genome editing using synthetic viruses will open up unprecedented possibilities for changing the properties of crop plants already growing in fields. Plants could, for example, be genetically altered to nearly instantly become less susceptible to pests or droughts. Until now, genetic engineering of commercial seeds always occurred in laboratories. With farmers planting seeds, needing to anticipate what environmental conditions will likely arise during a growing season. This means that, in the case of an unexpected drought, only farmers who had already planted drought-resistant seeds would gain a benefit. However, the originators of this project claim that genetic engineering in fields would offer farmers the possibility to alter the genetic properties of their crops at any time. Use of this technology would represent a radical break with many existing farming practices, potentially jeopardizing their coexistence.At the end of 2016, DARPA (Defense Advanced Research Projects Agency) put out a call for tenders for a 4-year research work plan. This program has distributed a total of 27 million US dollars, aiming to develop genetically modified viruses that can genetically edit crops in fields. The first of three consortia, drawn from 14 American research facilities, announced their participation in mid-2017. Maize and tomato plants are reportedly being used in current experiments, while dispersal insect species mentioned include leafhoppers, whiteflies, and aphids. The DARPA work plan will culminate in large-scale greenhouse demonstrations of the fully functional system including insect-dispersed viruses.In public statements, DARPA asserts that developments resulting from the Insect Allies Program are intended for routine agricultural use, for example for protecting crops against droughts, frost, flooding, pesticides or diseases. However, most countries using such technology would require comprehensive changes to approval processes for genetically modified organisms. Farmers, seed producers and not least the general public would also be massively affected by a use of such methods. "There is hardly any public debate about the far-reaching consequences of proposing the development of this technology. The Insect Allies programme is largely unknown, even in expert circles," says Guy Reeves of the Max Planck Institute for Evolutionary Biology in Plön.However, scientists and legal scholars from Plön, Freiburg and Montpellier believe that a broad social, scientific and legal debate of the issue is urgently required. Among other concerns it is their opinion, that no compelling reasons have been presented by DARPA for the use of insects as an uncontrolled means of dispersing synthetic viruses into the environment. Furthermore, they argue the findings of the Insect Allies Program could be more easily used for biological warfare than for routine agricultural use. "It is very much easier to kill or sterilize a plant using gene editing than it is to make it herbicide or insect-resistant," explains Reeves. Considering these, and other, concerns articulated in the Science article, the DARPA programme risks being perceived as a program that is not justified for peaceful purposes, as is required according to the Biological Weapons Convention. This, in turn, may lead to other countries developing their own weapons in this area.In international law, the decisive factor is whether a biological research programme exclusively serves peaceful purposes. The Biological Weapons Convention, to which more than 180 States are parties, obliges all parties to never under any circumstances develop or produce agents or toxins of types or in quantities "that have no justification for prophylactic, protective or other peaceful purposes." In addition, the Convention prohibits to develop or produce "weapons, equipment or means of delivery designed to use such agents or toxins for hostile purposes or in armed conflict." The authors argue that the insects used to deliver the viral agents might be perceived as means of delivery in terms of the Convention."Because of the broad ban of the Biological Weapons Convention, any biological research of concern must be plausibly justified as serving peaceful purposes. The Insect Allies Program could be seen to violate the Biological Weapons Convention, if the motivations presented by DARPA are not plausible. This is particularly true considering that this kind of technology could easily be used for biological warfare," explains Silja Vöneky, a law professor from Freiburg University.The authors of the Science article are also concerned that the Insect Allies Program might encourage other states to increase their own research activities in this field -- regardless of whether this program proves to be technically successful or not. Past efforts for banning the development of biological weapons have shown how important it is that this ban be applied by states such as the USA, who are considered an example by other countries. Based on this, the authors propose that the US should make proactive efforts to avoid any suspicion of engaging technologies that have the alarming potential for use in biological warfare.
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October 4, 2018
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https://www.sciencedaily.com/releases/2018/10/181004100009.htm
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Periodontal disease bacteria may kick-start Alzheimer's
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Long-term exposure to periodontal disease bacteria causes inflammation and degeneration of brain neurons in mice that is similar to the effects of Alzheimer's disease in humans, according to a new study from researchers at the University of Illinois at Chicago.
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The findings, which are published in "Other studies have demonstrated a close association between periodontitis and cognitive impairment, but this is the first study to show that exposure to the periodontal bacteria results in the formation of senile plaques that accelerate the development of neuropathology found in Alzheimer's patients," said Dr. Keiko Watanabe, professor of periodontics at the UIC College of Dentistry and corresponding author on the study."This was a big surprise," Watanabe said. "We did not expect that the periodontal pathogen would have this much influence on the brain, or that the effects would so thoroughly resemble Alzheimer's disease."To study the impact of the bacteria on brain health, the Watanabe and her colleagues -- including Dr. Vladimir Ilievski, UIC research assistant professor and co-author on the paper -- established chronic periodontitis, which is characterized by soft tissue damage and bone loss in the oral cavity, in 10 wild-type mice. Another 10 mice served as the control group. After 22 weeks of repeated oral application of the bacteria to the study group, the researchers studied the brain tissue of the mice and compared brain health.The researchers found that the mice chronically exposed to the bacteria had significantly higher amounts of accumulated amyloid beta -- a senile plaque found in the brain tissue of Alzheimer's patients. The study group also had more brain inflammation and fewer intact neurons due to degeneration.These findings were further supported by amyloid beta protein analysis, and RNA analysis that showed greater expression of genes associated with inflammation and degeneration in the study group. DNA from the periodontal bacteria was also found in the brain tissue of mice in the study group, and a bacterial protein was observed inside their neurons."Our data not only demonstrate the movement of bacteria from the mouth to the brain, but also that chronic infection leads to neural effects similar to Alzheimer's," Watanabe said.The researchers say these findings are powerful in part because they used a wild-type mouse model; most model systems used to study Alzheimer's rely on transgenic mice, which have been genetically altered to more strongly express genes associated with the senile plaque and enable Alzheimer's development."Using a wild-type mouse model added strength to our study because these mice were not primed to develop the disease, and use of this model gives additional weight to our findings that periodontal bacteria may kick-start the development of the Alzheimer's," Watanabe said.The researchers say that understanding causality and risk factors for the development of Alzheimer's is critical to the development of treatments, particularly when it comes to sporadic, or late-onset disease, which constitutes more than 95 percent of cases and has largely unknown causes and mechanisms.While the findings are significant for the scientific community, Watanabe said there are lessons for everyone."Oral hygiene is an important predictor of disease, including diseases that happen outside the mouth," she said. "People can do so much for their personal health by taking oral health seriously."Additional co-authors on the paper are Paulina Zuchowska, Stefan Green, Peter Toth, Michael Ragozzino, Khuong Le and Haider Aljewari of UIC, and Neil O'Brein-Simpson and Eric Reynolds of the University of Melbourne.
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October 2, 2018
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https://www.sciencedaily.com/releases/2018/10/181002102803.htm
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Commandeering microbes pave way for synthetic biology in military environments
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A team of scientists from the U.S. Army Research Laboratory and the Massachusetts Institute of Technology have developed and demonstrated a pioneering synthetic biology tool to deliver DNA programming into a broad range of bacteria.
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This research was recently published in the journal The research was sponsored, in large part, by the Office of the Secretary Defense through a Laboratory University Collaborative Initiative, or LUCI, program to provide early access and accelerate Department of Defense laboratory innovation through partnership and collaboration with leading scientists across the nation.ARL researchers said they recognize the high maturation rate in the field of synthetic biology demands "strong ties to the broader community to take advantage of advancements and to influence the field as it progresses."That acceleration, in this case, is the Army's ability to genetically engineer undomesticated microbes that either thrive in austere environments or, in many cases, access high value specialty material sets not possible with current technology."Much of the current work in synthetic biology has used a small number of domesticated microbes, including E. coli or yeast," said Dr. Bryn Adams of ARL's Biotechnology Branch. "Unlocking genetic access to undomesticated microbes has been a major barrier to military adoption of synthetic biology products."Adams further explained that there is a need for broadly applicable synthetic biology tools that allow access to a wide range of microorganisms, including the most fundamental step of genetic engineering the ability to transfer DNA into a cell.The team's novel approach to address this problem uses an engineered Bacillus subtilis bacterium, termed XPORT, to deliver DNA in a highly precise and controlled fashion to a wide variety of bacteria.The XPORT bacteria facilitated multiple demonstrations of newly programmed function, including fluorescent protein reporting, in 35 different bacteria, some of which were never before identified let alone characterized as they were only recently isolated from a soil moisture sensor at the laboratory.In discussing the pervasive presence of bacteria in every environment and access to these microbes for the first time, MIT professor and corresponding author Dr. Christopher Voigt said, "Every Soldier, vehicle and weapon system is coated with living bacteria. We are looking forward to understanding how these bacteria change depending on the theater, now having the ability to control them for sustained optimal performance."This research is a prelude to the first DOD service laboratory synthetic biology program, termed Living Materials, set to officially launch in October 2018.The long-term vision of this program is to impart living, reactive and responsive functions to materials for operation in Army relevant environments yielding disruptive capabilities, such as tunable assembled materials, self-healing and adaptation for advanced protection and transformative logistics.The ARL Living Materials program lead and manuscript co-author Dr. Dimitra Stratis-Cullum explained "The next frontier in synthetic biology will bring unprecedented advances in high performance and smart materials, but will require moving the state-of-the-art from production of molecules to materials as well as from the laboratory to the field. This necessitates the Army to drive advances in tools for military relevant chassis and to bridge the gap in structure function relationships for high performance military materials."This research also has significant impacts outside of the DOD, the scientists said."In the paper, we demonstrate XPORT's flexibility by engineering bacteria isolated from human skin, human feces and agricultural soil," said lead author Dr. Jennifer Brophy. "Microbes from these environments are good candidates for probiotics that are engineered to enhance human health or agriculture."Army scientists believe it is imperative that the Army act now in order to counter adversaries who will leverage these advances for next generation threats in the future operational environment.
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Genetically Modified
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October 1, 2018
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https://www.sciencedaily.com/releases/2018/10/181001114232.htm
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Immune cells help older muscles heal like new
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Biomedical engineers at Duke University have found a critical component for growing self-healing muscle tissues from adult muscle -- the immune system. The discovery in mice is expected to play an important role in studying degenerative muscle diseases and enhancing the survival of engineered tissue grafts in future cell therapy applications.
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The results appeared online October 1 in In 2014, the group led by Nenad Bursac, professor of biomedical engineering at Duke, debuted the world's first self-healing, lab-grown skeletal muscle. It contracted powerfully, integrated into mice quickly and demonstrated the ability to heal itself both inside the laboratory and inside an animal.The milestone was achieved by taking samples of muscle from rats just two days old, removing the cells, and "planting" them into a lab-made environment perfectly tailored to help them grow. Besides a three-dimensional scaffolding and plenty of nutrients, this environment supported the formation of niches for muscle stem cells, known as satellite cells, that activate upon injury and aid the regeneration process.For potential applications with human cells, however, muscle samples would be mostly taken from adult donors rather than newborns. Many degenerative muscle diseases do not appear until adulthood, and growing the muscle in the lab to test drug responses for these patients would benefit from the use of the patient's own adult cells.There's just one problem -- lab-made adult muscle tissues do not have the same regenerative potential as newborn tissue."I spent a year exploring methods to engineer muscle tissues from adult rat samples that would self-heal after injury," said Mark Juhas, a former Duke doctoral student in Bursac's lab who led both the original and new research."Adding various drugs and growth factors known to help muscle repair had little effect, so I started to consider adding a supporting cell population that could react to injury and stimulate muscle regeneration," said Juhas. "That's how I came up with macrophages, immune cells required for muscle's ability to self-repair in our bodies."Macrophages are a type of white blood cell in the body's immune system. Literally translated from Greek as "big eaters," macrophages engulf and digest cellular debris, pathogens and anything else they don't think should be hanging around while also secreting factors that support tissue survival and repair.After a muscle injury, one class of macrophages shows up on the scene to clear the wreckage left behind, increase inflammation and stimulate other parts of the immune system. One of the cells they recruit is a second kind of macrophage, dubbed M2, that decreases inflammation and encourages tissue repair. While these anti-inflammatory macrophages had been used in muscle-healing therapies before, they had never been integrated into a platform aimed at growing complex muscle tissues outside of the body.It took several additional months of work for Juhas to figure out how to incorporate macrophages into the system. But once he did, the results changed dramatically. Not only did the new muscle tissues perform better in the laboratory, they performed better when grafted into live mice."When we damaged the adult-derived engineered muscle with a toxin, we saw no functional recovery and muscle fibers would not build back," said Bursac, who is a co-director of Duke's Regeneration Next initiative. "But after we added the macrophages in the muscle, we had a wow moment. The muscle grew back over 15 days and contracted almost like it did before injury. It was really remarkable."The success appears to stem primarily from macrophages acting to protect damaged muscle cells from apoptosis -- programmed cell death. While newborn muscle cells naturally resist the urge to throw in the towel, adult muscle cells need the macrophages to help them push through initial damage without going into cell death. These surviving muscle fibers then provide a "scaffold" for muscle stem cells to latch onto to perform their regenerative duties.Bursac believes the discovery may lead to a new line of research for potential regenerative therapies. According to a popular theory, fetal and newborn tissues are much better at healing than adult tissues at least in part because of an initial supply of tissue-resident macrophages that are similar to M2 macrophages. As individuals age, this original macrophage supply is replaced by less regenerative and more inflammatory macrophages coming from bone marrow and blood."We believe that the macrophages in our engineered muscle system may behave more like the muscle-resident macrophages people are born with," said Bursac. "We are currently working to understand if this is indeed the case. One could then envision 'training' macrophages to be better healers in a system like ours or augmenting them by genetic modifications and then implanting them into damaged sites in patients."That work is, of course, still years into the future. While this study also showed that human macrophages support the healing of lab-grown rat muscle, and separate work in Bursac's group has grown complex human muscles containing macrophages, there is not yet a good lab or animal system to test the regenerative powers that this approach may have in humans."Building a platform to test these results in engineered human tissues is a clear next step," said Bursac. "Along the same lines, we want to better understand the potential roles that macrophages within engineered muscle play in its vascularization and innervation after implantation. We hope that our approach of supplementing lab-grown muscles with immune system cells will prove to be a general strategy to augment survival and function of other lab-grown tissues in future regeneration therapies."
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Genetically Modified
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October 1, 2018
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https://www.sciencedaily.com/releases/2018/10/181001114217.htm
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Pioneering biologists create a new crop through genome editing
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Crops such as wheat and maize have undergone a breeding process lasting thousands of years, in the course of which humankind has gradually modified the properties of the wild plants in order to adapt them to his needs. One motive was, and still is, higher yields. One "side effect" of this breeding has been a reduction in genetic diversity and the loss of useful properties. This is shown, among others, by an increased susceptibility to diseases, a lack of taste or a reduced vitamin and nutrient content in modern varieties. Now, for the first time, researchers from Brazil, the USA and Germany have created a new crop from a wild plant within a single generation using CRISPR-Cas9, a modern genome editing process. Starting with a "wild tomato" they have, at the same time, introduced a variety of crop features without losing the valuable genetic properties of the wild plant. The results have been published in the current issue of
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"This new method allows us to start from scratch and begin a new domestication process all over again," says biologist Prof. Jörg Kudla from the University of Münster (Germany), whose team is involved in the study. "In doing so, we can use all the knowledge on plant genetics and plant domestication which researchers have accumulated over the past decades. We can preserve the genetic potential and the particularly valuable properties of wild plants and, at the same time, produce the desired features of modern crops in a very short time." Altogether, the researchers spent about three years working on their studies.The researchers chose The researchers modified the wild plant by using "multiplex CRISPR-Cas9" in such a way that the offspring plants bore small genetic modifications in six genes. These decisive genes had already been recognized by researchers over the past few years and are seen as the genetic key to features in the domesticated tomato. Specifically, the researchers produced the following modifications in comparison with the wild tomato: the fruit is three times larger than that of the wild tomato, which corresponds to the size of a cherry tomato. There is ten times the number of fruits, and their shape is more oval than the round wild fruit. This property is popular because, when it rains, round fruits split open faster than oval fruits. The plants also have a more compact growth.Another important new property is that the lycopene content in the new breed of tomato is more than twice as high as in the wild parent -- and no less than five times higher than in conventional cherry tomatoes. "This is a decisive innovation which cannot be achieved by any conventional breeding process with currently cultivated tomatoes," says Jörg Kudla. "Lycopene can help to prevent cancer and cardiovascular diseases. So, from a health point of view, the tomato we have created probably has an additional value in comparison with conventional cultivated tomatoes and other vegetables which only contain lycopene in very limited quantities." So far, he adds, breeders have tried in vain to increase the lycopene content in cultivated tomatoes. In cases in which they were successful, however, this was at the expense of the beta-carotene content -- which also protects cells and is therefore a valuable ingredient.Jörg Kudla sums up the dilemma of modern agriculture: "Our modern crops are the result of breeding -- with all its advantages and disadvantages. A lot of properties, such as resilience, have been lost and we would only be able to regain them through a laborious, decades-long process of backcrossing with the wild plant -- if at all. The reason is that properties that are the result of the interplay between numerous genes cannot be restored through traditional breeding processes. In many aspects, domestication is like a one-way street. With the help of modern genome editing, we can use the advantages of the wild plant and solve this breeding problem. In brief, molecular 'de novo domestication' offers enormous potential -- also for producing new, desirable properties." Moreover, adds Prof. Kudla, it will now be possible, for example, to take plants which are very healthy -- but which have not so far been used by humans, or only to a very limited extent -- and, by means of a targeted increase in the size of their fruit or by improving other features of domestication, transform them into entirely new crops.Details of the method: The researchers used the CRISPR-Cas9 method to target and deactivate genes in the
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Genetically Modified
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September 27, 2018
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https://www.sciencedaily.com/releases/2018/09/180927105706.htm
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Genetically engineered viruses discern, destroy E. coli in drinking water
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To rapidly detect the presence of
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Rather than sending water samples to laboratories and waiting days for results, this new test can be administered locally to obtain answers within hours, according to new research published by The Royal Society of Chemistry, August 2018."Drinking water contaminated with The bacteriophage T7NLC carries a gene for an enzyme NLuc luciferase, similar to the protein that gives fireflies radiance. The luciferase is fused to a carbohydrate (sugar) binder, so that when the bacteriophage finds the After the bacteriophage binds to the Said Nugen: "This bacteriophage detects an indicator. If the test determines the presence of First author Troy Hinkley, a Cornell doctoral candidate in the field of food science, is working as an intern with Intellectual Ventures/Global Good, a group that focuses on philanthropic, humanitarian scientific research, to further develop this bacteriophage.Describing the importance of phage-based detection technology, Hinkley said, "Global Good invents and implements technologies to improve the lives of people in the developing world. Unfortunately, improper sanitation of drinking water leads to a large number of preventable diseases worldwide."Phage-based detection technologies have the potential to rapidly determine if a water source is safe to drink, a result that serves to immediately improve the quality of life of those in the community through the prevention of disease," he said.
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Genetically Modified
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September 24, 2018
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https://www.sciencedaily.com/releases/2018/09/180924112747.htm
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DNA islands effective as 'anti-bacterial drones'
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Genomic "islands" that evolved from viruses can be converted into "drones" that disable
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Conducted by researchers from NYU School of Medicine and published online in the journal The type of DNA featured in the study, a "pathogenicity island," evolved from viruses that stayed permanently in the bacteria they infected to become a part of their genetic system. The result is a hybrid entity that contains useful genes passed on by the bacteria when they reproduce, but that is also in some cases cut out of the bacterial superstructure, and packaged like a virus in a protein shell (capsid) that can inject its DNA into other bacterial cells.This mix of evolutionary leaps has fashioned genomic islands as perfect drone-like vehicles to deliver genetic payloads throughout bacterial populations, say the study authors. When injected into mice with an otherwise lethal staph infection, the research team's engineered "Given efficacy seen so far, and the safety record of related treatment attempts, we are getting set to test our drones against a Staph infection that interferes with milk production in cattle, and if successful there, in humans with Staph infections," says senior study author Richard P. Novick, MD, the Recanati Family Professor of Science at the Skirball Institute of Biomolecular Medicine within NYU School of Medicine, and a member of the National Academy of Sciences."It is an extraordinarily rewarding experience to spend a long career studying an infection, and then to arrive at a potentially new way to treat it," says Novick, who earned his MD at NYU School of Medicine and has been studying Staph ever since.One-third of the human population are carriers of In addition, antibiotics used against Staph are becoming less effective because an increasing number of strains have become resistant to these drugs. With many Staph infections now untreatable after decades of antibiotic over-use, the field urgently seeks new ways to counter infections.It was during research in the 1980s on a gene called TSST1 -- which causes a dangerous complication of Staph infections called toxic shock syndrome -- that Novick and colleagues first discovered that a pathogenicity island carried TSST1 as part of its cargo. The team's subsequent drone design effort grew from the understanding that Staph bacteria depend on genomic islands to share useful genes. In this way, an entire population benefits when any one cell stumbles on a change that helps it to survive, and not just its offspring."The natural role of islands in such gene transfers set them up as a new treatment approach, if they could be made to contain genes that hampered bacteria instead of encouraging infection," says Hope Ross, PhD, a longtime member of the lab. In 2013, it was Ross that first saw this potential, and suggested that the lab focus on it.As a first test, the team added to their island a CRISPR/Cas9 sequence, a genetic system that targets and cuts the DNA chain within a targeted gene, a lethal event in bacteria. Another drone studied by the team contains a gene for the enzyme lysostaphin, which directly kills bacteria by breaking down their cell walls. The team also studied a CRISPR approach with the potential to disable several, disease-causing bacterial genes without killing the bacteria, which promises to prevent infections from becoming drone resistant.Novick's study also led to another important conclusion. "The drone system would not, like antibiotics, disrupt patients' microbiomes, the mix of bacteria in the gut, some species of which are essential to digestion and to general health," he says.
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Genetically Modified
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September 17, 2018
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https://www.sciencedaily.com/releases/2018/09/180917111609.htm
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Gene therapy via skin protects mice from lethal cocaine doses
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There are no approved medications to treat either cocaine addiction or overdose. Frequent users tend to become less and less sensitive to the drug, leading to stronger or more frequent doses. The typical result is addiction. Exposure to the drug, or to drug-associated cues, even after long periods of abstention, often leads to relapse.
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In the September 17, 2018 issue of The researchers had the three crucial mechanisms necessary to treat overdose and prevent addiction, according to Xu."We had an effective enzyme that can degrade cocaine with high efficiency," he said. "We had CRISPR, a genetic tool that enabled us to introduce a gene of interest inside the cell without affecting other genes. And, most importantly we had technology, developed by my colleague Xiaoyang Wu, to put genetically modified skin cells back into an immunocompetent recipient. That saved us a lot of trouble."The enzyme, butyrylcholinesterase (BChE), can degrade cocaine. But because of its short half-life, injecting BChE directly into muscle tissue has a profoundly limited effect.To make long-lasting BChE, the authors collected primary epidermal basal progenitor/stem cells from newborn mice. They used CRISPR to deliver engineered human BChE to the cells.Then they used a technique, developed by Wu, to prepare skin organoids and transplant them back to the donor animals, where they act as a depot for robust expression and secretion of hBChE into the blood stream. This efficiently protected the mice from cocaine-seeking and cocaine-induced relapse. It even prevented the death of mice exposed to uniformly lethal doses of cocaine.Cutaneous gene therapy can be used as a "safe and effective way for treatment of non-skin diseases, including drug abuse, a scenario that has not been explored before," the authors note. "We demonstrated key evidence that engineered skin transplants can efficiently deliver hBChE in vivo and protect against cocaine-seeking and overdose."These stem cells were well tolerated by the injected mice. The grafted skin cells exhibited normal epidermal stratification, proliferation and cell death.Mice who received these skin grafts were able to remove cocaine from the bloodstream much faster than normal mice. They were able to withstand cocaine overdoses that would be lethal to 100 percent of unprotected mice.Treated mice were less likely than untreated mice to enter environments previously associated with cocaine use. Mice exposed to alcohol, however, retained a learned fondness for that drug."Our study demonstrates that transplantation of genome-edited skin stem cells can be used to deliver an active cocaine hydrolase long term in vivo," the authors concluded. They showed that epidermal stem cells "can be successfully employed for ex vivo gene therapy, as efficient genetic manipulation is possible with minimal risk."Skin transplantation protocols have been in clinical use for decades in the treatment of burn wounds, as well as vitiligo and skin genetic disorders, the authors note. These regenerated skin grafts "are stable and have been shown to survive long-term."The skin-derived expression of hBChE in host mice with intact immune systems was stable for more than 10 weeks without significant decrease in hBChE. This suggests that the skin environment may limit any potential immune reaction toward hBChE.The oldest mice in this study are now 12 months old and healthy, the authors note, which supports the feasibility of cutaneous gene therapy. "Taken together, our results show promise of cutaneous gene therapy as a safe and cost-effective therapeutic option for cocaine abuse in the future."For cocaine addicts or those prone to cocaine abuse, this approach could reduce drug-seeking and protect against cocaine overdose, potentially making them "immune" to further cocaine abuse. This skin cell-based approach can potentially be used to treat alcohol, nicotine and opioid abuse and co-abuse.Creative thinking about cocaine addiction and overdose is needed. About five percent of young adults in the United States (1.7 million people aged 18 to 25) have used cocaine at least once, according to the 2015 National Survey on Drug Use and Health. More than 900,000 Americans are dependent on, or abuse, this popular but illegal drug.This study was funded by grants from the National Institutes of Health, the American Cancer Society and the V Foundation. Additional authors were Yuanyuan Li, Qingyao Kong, Jiping Yue and Xuewen Gou, all from the University of Chicago.
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Genetically Modified
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September 10, 2018
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https://www.sciencedaily.com/releases/2018/09/180910111249.htm
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Scientists block RNA silencing protein in liver to prevent obesity and diabetes in mice
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Obesity and its related ailments like type 2 diabetes and fatty liver disease pose a major global health burden, but researchers report in
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Takahisa Nakamura, PhD, and colleagues at Cincinnati Children's Hospital Medical Center genetically deleted a protein called Argonaute 2 (Ago2) from the livers of mice. Ago2 controls the silencing of RNA in cells, affecting energy metabolism in the body, according to the study. When Ago2 silences RNA in the liver, it slows metabolism and liver's ability to process a high-fat diet, the scientists report.When they deleted Ago2 from the livers of mice, it was not toxic to the animals but it did stabilize energy metabolism. This helped stave off obesity and prevented the mice from developing diabetes and fatty liver disease, which can severely damage the vital organ -- which helps rid the body of toxic substances."Although this is still basic science, we propose that there may be important translational implications for our findings for chronic metabolic disorders like diabetes, fatty liver diseases, and other obesity associated illnesses," said Nakamura, senior investigator and a member of the Division of Endocrinology. "This allows us to explore the potential of finding a novel therapeutic approach that alters energy balance in obesity and modulates the associated diseases."The scientists caution the research is early stage. Their findings still need additional study and verification in laboratory models and the development of a practical therapeutic to inhibit Ago2 in a clinical setting for patients. But the current paper provides a solid basis for subsequent work.Ago2 was identified after the researchers conducted a thorough screen and analysis of the activity of genes and their molecular targets in the liver, such as critical proteins. They analyzed wild type and genetically modified mice with high-fat diets by deleting certain proteins that are critical to liver metabolism -- such as one called AMPK (AMP-activated protein kinase).Nakamura said that identifying Ago2's role in the process "connects the dots" between how proteins are translated in the liver, how energy is produced and consumed and the activity of AMPK in these processes. He pointed out that disruption of these events is already a common feature in obesity and its related illnesses.
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Genetically Modified
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August 31, 2018
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https://www.sciencedaily.com/releases/2018/08/180831090941.htm
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Synthetic microbiome? Genetic engineering allows different species of bacteria to communicate
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More than 1,000 species of bacteria have been identified in the human gut, and understanding this incredibly diverse "microbiome" that can greatly impact health and disease is a hot topic in scientific research. Because bacteria are routinely genetically engineered in science labs, there is great excitement about the possibility of tweaking the genes of our intestinal interlopers so that they can do more than just help digest our food (e.g., record information about the state of the gut in real-time, report the presence of disease, etc.). However, little is known about how all those different strains communicate with each other, and whether it is even possible to create the kinds of signaling pathways that would allow information to be passed between them.
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Now, researchers from the Wyss Institute at Harvard University, Harvard Medical School (HMS), and Brigham and Women's Hospital have successfully engineered a genetic signal-transmission system in which a molecular signal sent by Salmonella Typhimurium bacteria in response to an environmental cue can be received and recorded by "In order to improve human health through engineered gut bacteria, we need to start figuring out how to make the bacteria communicate," said Suhyun Kim, a graduate student in the lab of Pamela Silver at the Wyss Institute and HMS, who is the first author of the paper. "We want to make sure that, as engineered probiotics develop, we have a means to coordinate and control them in harmony."The team harnessed an ability that naturally occurs in some strains of bacteria called "quorum sensing," in which the bacteria send and receive signal molecules that indicate the overall density of the bacterial colony and regulate the expression of many genes involved in group activities. A particular type of quorum sensing known as acyl-homoserine lactone (acyl-HSL) sensing has not yet been observed in the mammalian gut, so the team decided to see if they could repurpose its signaling system to create a bacterial information transfer system using genetic engineering.The researchers introduced two new genetic circuits into different colonies of a strain of The researchers confirmed that this system works in vitro in both "It was exciting and promising that our system, with single copy-based circuits, can create functional communication in the mouse gut," explained Kim. "Traditional genetic engineering introduces multiple copies of a gene of interest into the bacterial genome via plasmids, which places a high metabolic burden on the engineered bacteria and causes them to be easily outcompeted by other bacteria in the host."Finally, the team repeated the in vivo experiment, but gave the mice signaler The researchers hope to continue this line of inquiry by engineering more species of bacteria so that they can communicate, and by searching for and developing other signaling molecules that can be used to transmit information between them."Ultimately, we aim to create a synthetic microbiome with completely or mostly engineered bacteria species in our gut, each of which has a specialized function (e.g., detecting and curing disease, creating beneficial molecules, improving digestion, etc.) but also communicates with the others to ensure that they are all balanced for optimal human health," said corresponding author Silver, Ph.D., a Founding Core Faculty member of the Wyss Institute who is also the Elliot T. and Onie H. Adams Professor of Biochemistry and Systems Biology at HMS."The microbiome is the next frontier in medicine as well as wellness. Devising new technologies to engineer intestinal microbes for the better while appreciating that they function as part of a complex community, as was done here, represents a major step forward in this direction," said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at SEAS.
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Genetically Modified
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August 25, 2018
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https://www.sciencedaily.com/releases/2018/08/180825132319.htm
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Genetic analysis of Florida's invasive pythons reveals a tangled family tree
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A new genetic analysis of invasive pythons captured across South Florida finds the big constrictors are closely related to one another. In fact, most of them are genetically related as first or second cousins, according to a study by wildlife genetics experts at the U.S. Geological Survey.
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The study also found that at least a few of the snakes in the invasive South Florida population are not 100 percent Burmese pythons. Instead, the genetic evidence shows at least 13 snakes out of about 400 studied are a cross between two separate species: Burmese pythons, which mostly inhabit wetlands, and Indian pythons, which prefer higher ground. The interbreeding between Burmese and Indian pythons probably took place before the animals became established in the South Florida environment, and may have given them greater adaptability in their new habitats.The South Florida pythons spring from a tangled family tree, with consequences for the species' future spread that are hard to predict, the USGS scientists said."The snakes in South Florida are physically identifiable as Burmese pythons, but genetically, there seems to be a different, more complicated story," said Margaret Hunter, a USGS research geneticist and lead author on the study published in the journal Burmese pythons have been reproducing in the Everglades since the 1980s, and have caused important environmental changes including the decline of small-mammal populations in South Florida.The researchers analyzed tail tissue from about 400 Burmese pythons captured across a wide area, from southwest Florida and the Big Cypress National Preserve to the Everglades, southeast Miami-Dade County and the Florida Keys, between 2001 and 2012.The researchers looked at nuclear DNA, which contains genetic material from both parents, to determine how much each animal had in common with others in the population. To express family relationships in statistical terms, they used a common type of calculation known as a relatedness value. For all snakes in the study, the average relatedness value was about midway between first and second cousins. That close kinship means the population as a whole is experiencing inbreeding, the researchers concluded.When the researchers tested genetic material from a different part of the snakes' cells-mitochondrial DNA, inherited solely from the mother-they were surprised to find genetic signatures from the Indian python in 13 snakes.Sometimes interbreeding between related species "can lead to hybrid vigor, that is, the best traits of two species are passed onto their offspring," Hunter saidIn the wild, related species typically avoid interbreeding by using different habitats. In their native Asia, Burmese pythons prefer wet habitats, while Indian pythons tend to stick to drier ones. In previous studies, scientists have observed South Florida's Burmese pythons in both wet and dry habitat types."Our ability to detect Burmese pythons in the Greater Everglades has been limited by their effective camouflage and secretive behavior," said Kristen Hart, a USGS research ecologist and a co-author on the study. "By using genetic tools and techniques and continuing to monitor their movement patterns, we have been able to gain a better understanding of their habitat preferences and resource use. The new information in this study will help scientists and wildlife managers better understand these invasive predators' capacity to adapt to new environments."
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Genetically Modified
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August 24, 2018
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https://www.sciencedaily.com/releases/2018/08/180824090616.htm
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Genetically engineered virus spins gold into beads
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The race is on to find manufacturing techniques capable of arranging molecular and nanoscale objects with precision.
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Engineers at the University of California, Riverside, have altered a virus to arrange gold atoms into spheroids measuring a few nanometers in diameter. The finding could make production of some electronic components cheaper, easier, and faster."Nature has been assembling complex, highly organized nanostructures for millennia with precision and specificity far superior to the most advanced technological approaches," said Elaine Haberer, a professor of electrical and computer engineering in UCR's Marlin and Rosemary Bourns College of Engineering and senior author of the paper describing the breakthrough. "By understanding and harnessing these capabilities, this extraordinary nanoscale precision can be used to tailor and build highly advanced materials with previously unattainable performance."Viruses exist in a multitude of shapes and contain a wide range of receptors that bind to molecules. Genetically modifying the receptors to bind to ions of metals used in electronics causes these ions to "stick" to the virus, creating an object of the same size and shape. This procedure has been used to produce nanostructures used in battery electrodes, supercapacitors, sensors, biomedical tools, photocatalytic materials, and photovoltaics.The virus' natural shape has limited the range of possible metal shapes. Most viruses can change volume under different scenarios, but resist the dramatic alterations to their basic architecture that would permit other forms.The M13 bacteriophage, however, is more flexible. Bacteriophages are a type of virus that infects bacteria, in this case, gram-negative bacteria, such as Studies of the infection process of the M13 bacteriophage have shown the virus can be converted to a spheroid upon interaction with water and chloroform. Yet, until now, the M13 spheroid has been completely unexplored as a nanomaterial template.Haberer's group added a gold ion solution to M13 spheroids, creating gold nanobeads that are spiky and hollow."The novelty of our work lies in the optimization and demonstration of a viral template, which overcomes the geometric constraints associated with most other viruses," Haberer said. "We used a simple conversion process to make the M13 virus synthesize inorganic spherical nanoshells tens of nanometers in diameter, as well as nanowires nearly 1 micron in length."The researchers are using the gold nanobeads to remove pollutants from wastewater through enhanced photocatalytic behavior.The work enhances the utility of the M13 bacteriophage as a scaffold for nanomaterial synthesis. The researchers believe the M13 bacteriophage template transformation scheme described in the paper can be extended to related bacteriophages.The paper, "M13 bacteriophage spheroids as scaffolds for directed synthesis of spiky gold nanostructures," was published in the July 21 issue of The project is supported by award number N00014-14-1-0799 from the U.S. Office of Naval Research.
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Genetically Modified
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August 22, 2018
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https://www.sciencedaily.com/releases/2018/08/180822141029.htm
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Found: A destructive mechanism that blocks the brain from knowing when to stop eating
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An international team of researchers has uncovered a destructive mechanism at the molecular level that causes a well-known phenomenon associated with obesity, called leptin resistance.
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They found that mice fed a high-fat diet produce an enzyme named MMP-2 that clips receptors for the hormone leptin from the surface of neuronal cells in the hypothalamus. This blocks leptin from binding to its receptors. This in turn keeps the neurons from signaling that your stomach is full and you should stop eating.This is the first time that a destructive molecular mechanism has been observed and described.Scientists showed that when MMP-2 is blocked, leptin can still bind to the receptors and signal satiety. They hope that in the future, clinicians will be able to treat leptin resistance in humans by blocking MMP-2. They also have evidence that their findings have a broader scope."We opened a new field of study for metabolic disease," said Rafi Mazor, a research scientist in the Department of Bioengineering at the University of California San Diego and the paper's first author. "We need to ask what other pathways, in addition to leptin and its receptors, undergo a similar destructive process and what the consequences might be."Mazor is part of a team that includes researchers from the University of California San Diego, the Salk Institute for Biological Studies in La Jolla, Tel Aviv University in Israel and Monash University in Australia. The team presents their findings in the Aug. 23 issue of While other research efforts have focused on studying pathways that block leptin from doing its job, Mazor and colleagues, under the lead of UC San Diego bioengineering professor Geert Schmid-Schonbein, decided to investigate the leptin receptor in the brain itself."Our hypothesis was that an enzyme breaking down proteins into amino acids and polypeptides can cleave membrane receptors and lead to dysfunctional activity," Mazor said.He and colleagues are calling for a large-scale clinical trial to investigate whether MMP-2 inhibitors might help people lose weight. Those in the early stages of being overweight might be clipping their leptin receptors, but their neural pathways are still intact, Schmid-Schonbein said. Receptors are able to regenerate but it's unclear to what extent."When you block the protease that leads to the receptors not signaling, you can treat the issue," said Schmid-Schonbein.Leptin molecules are released from white fat tissue during a meal. They travel through the blood stream into the brain, specifically the hypothalamus, where they stimulate neural receptors to signal that the stomach is full. People who are obese often have plenty of leptin in their blood, but it fails to lead to signaling satiety.Leptin resistance is a known process associated with obesity, but the molecular mechanisms by which it occurs were not understood.Researchers first tested brain tissue from obese mice for protease activity. This is how they found MMP-2, the enzyme that they suspected was damaging leptin receptors. Mazor and colleagues then developed a method to tag leptin receptors to see what was happening to them. They observed that MMP-2 was damaging the receptors, which lost their ability to signal. Researchers then used a recombinant protein to verify that the MMP-2 enzyme was indeed cleaving leptin receptors. They also cultured brain cells from mice and found clipped receptors when MMP-2 was present.Researchers genetically altered a group of mice to not produce MMP-2. In spite of being fed a high-fat diet, these mice gained less weight and their leptin receptors remained intact. Meanwhile, mice that were fed the same diet but were not genetically altered became obese and their leptin receptors were cleaved.In the long run, researchers aim to design an MMP-2 inhibitor or an inhibitor for the MMP-2 pathway of activation. Next steps also include confirming that the same mechanism occurs in human brain cells. "In the future, we will try to find out why proteases are activated, what is activating them and how to stop it," Mazor added. He and the team think that other membrane receptors may also be destroyed in the same way. "There is still a lot of work to do to better understand receptor cleaving and the loss of cell function while on a high-fat diet."
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Genetically Modified
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August 21, 2018
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https://www.sciencedaily.com/releases/2018/08/180821094234.htm
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Bigger proteins, stronger threads: Synthetic spider silk
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Spider silk is among the strongest and toughest materials in the natural world, as strong as some steel alloys with a toughness even greater than bulletproof Kevlar. Spider silk's unmatched combination of strength and toughness have made this protein-based material desirable for many applications ranging from super thin surgical sutures to projectile resistant clothing. Unfortunately, due to spiders' territorial and cannibalistic nature, their silk has been impossible to mass produce, so practical applications have yet to materialize.
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Scientists have been able to create some forms of synthetic spider silk, but have been unable to engineer a material that included most if not all of the natural silk's traits.Until now.Researchers in the School of Engineering & Applied Science at Washington University in St. Louis have engineered bacteria that produce a biosynthetic spider silk with performance on par with its natural counterparts in all of the important measures. And they've discovered something exciting about the possibilities ahead.The new research, published Monday, Aug. 20 in "People already knew about this correlation, but only with smaller-sized proteins. We found that even at this large size, there is still a very good correlation," said Fuzhong Zhang, associate professor in the School of Engineering & Applied Science.One of the biggest historical challenges creating a biosynthetic spider silk has been creating a large enough protein. The challenge was so big, in fact, it required a whole new approach."We started with what others had done, making a genetically repeated sequence," said Christopher Bowen, a PhD student in Zhang's lab. The DNA sequence was modeled after the sequence in spiders that is responsible for creating the silk protein. In theory, the more repetitions of the sequence, the bigger the resulting protein.After the DNA sequence reaches a certain size, however, "the bacteria can't handle it, they chop the sequence into smaller pieces," Bowen said. It's a problem has been encountered many times in previous efforts. To get around this long-standing obstacle, Bowen and co-authors added a short genetic sequence to the silk DNA that promotes a chemical reaction between the resulting proteins, fusing them together to form an even bigger protein, bigger than has ever been produced and purified before."We made proteins basically twice as large as anyone's been able to make before," Bowen said. Their silk protein chains are 556 kDa. Previously, the largest biosynthetic spider silk protein was 285 kDa. Even natural dragline silk proteins tend be around 370 kDa, although there are a few, bigger outliers.Bowen and co-authors subsequently spun their exceptionally large biosynthetic silk proteins into fibers about a tenth the diameter of a human hair and tested their mechanical properties. This biosynthetic silk is the first to replicate natural spider silk in terms of: tensile strength (the maximum stress needed to break the fiber), toughness (the total energy absorbed by the fiber before breaking), as well as other mechanical parameters such as elastic modulus and extensibility.Going forward, Zhang's lab is looking to work toward positioning biosynthetic silk fibers to replace some of the myriad of petroleum-based synthetic fibers used across industry."We will continue to work on making the process more scalable and economical by making it easier to handle, reducing the amount of chemicals needed, and increasing the robustness and efficiency," Zhang said.And the Zhang group also plans to further explore the limits of their new approach. In addition to producing the first biosynthetic silk fibers to fully replicate the performance of natural spider silk, their work strongly suggests that the strength and toughness of these fibers will continue to increase if even larger proteins can be produced.
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Genetically Modified
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August 14, 2018
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https://www.sciencedaily.com/releases/2018/08/180814134207.htm
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Models give synthetic biologists a head start
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Synthetic biologists have the tools to build complex, computer-like DNA circuits that sense or trigger activities in cells, and thanks to scientists at Rice University and the University of Houston they now they have a way to test those circuits in advance.
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Rice synthetic biologist Matthew Bennett and University of Houston mathematician William Ott led the development of models to predict the output of custom-built genetic circuits that, for example, can be prompted to start or stop the production of proteins. Their work is described in the American Chemical Society journal The idea behind synthetic biological circuits seems simple. They are combinations of proteins and ligands that switch gene expression on or off in response to specific conditions in a cell. Such circuits can be used to engineer bacteria and other organisms to regulate cellular systems or perform functions they wouldn't in nature.The approach allows unprecedented precision in programming microorganisms, and experts expect the field to bring about a revolution in biological sensing and delivery of customized medical treatments such as probiotics to patients and to advance the controllable manufacture of useful chemicals by genetically modified bacteria.The concern is that the ability to engineer new circuits, with hundreds of genetic parts available to combine in thousands of ways, has outstripped the ability to characterize them. And the same combination can lead to different outcomes depending on the cellular environment. Bennett said the new work is a step toward solving those problems by eliminating much of the trial and error.Bennett and Ott's initial modeling target is multi-input synthetic promoters, switches that require more than one condition to be met before they start or stop the production of a specific protein. For instance, a promoter could be designed to sense the environment around the cell and trigger production of a particular protein only if two chemicals are detected."One of the first problems in synthetic biology was just getting enough parts to assemble larger circuits," Bennett said. "Now that we have the parts, and we're faced with the task of being able to predict how these novel circuits are going to behave."There are different ways of constructing multi-input promoters, the parts of DNA that turn a gene on and off," Bennett said. "These constructs allow cells to sense multiple environmental conditions simultaneously to determine whether or not a gene should be turned on or off."Bennett said the team explored different ways of modeling systems to predict how they work. The models used information from the input/output relations of simple, stand-alone circuits, and then predict how they'll work in combination.The first "naïve" model used data from single-input systems that sense the presence of ligands that repress transcription by chimeric transcription factors. Combining data from several circuits allowed researchers to accurately predict the on-off responses in two-input circuits with two chimeras.The Rice lab confirmed the model's prediction by engineering bacteria with chimeric "AND" gates that required two ligands to be present to induce the production of a fluorescent protein. Changing the ligand levels changed the fluorescent output on a curve that closely matched the model's prediction.Bennett said a second, more sophisticated model predicts a circuit's output over an entire landscape of input combinations. That required "informing" the model with a small set of data from experimental two-input systems, and more experiments to verify the accuracy of the model.The lab also tested each model on multi-input hybrid promoters that included both activators (on switches) and repressors (off switches). The naïve model sometimes succumbed to crosstalk between signaling molecules, but the informed model continued to produce accurate predictions."This provides a way of designing and constructing large synthetic gene circuits more efficiently," Bennett said. "In the same way that we can predict how electronic circuits work before we build them by modeling them in computers, now we can do that with these gene circuits as well."He said the naïve model will be useful for predicting the behavior of well-characterized single-input devices without additional lab work, and the informed model will help researchers design microbes for complex, constantly changing environments such as the gut microbiome or soil.
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Genetically Modified
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August 13, 2018
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https://www.sciencedaily.com/releases/2018/08/180813160531.htm
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Scarlet macaw DNA points to ancient breeding operation in Southwest
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Somewhere in the American Southwest or northern Mexico, there are probably the ruins of a scarlet macaw breeding operation dating to between 900 and 1200 C.E., according to a team of archaeologists who sequenced the mitochondrial DNA of bird remains found in the Chaco Canyon and Mimbres areas of New Mexico.
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Remains of a thriving prehistoric avian culture and breeding colony of scarlet macaws exist at the northern Mexican site of Paquimé, or Casas Grande. However, this community existed from 1250 to 1450, well after the abandonment of Chaco Canyon, and could not have supplied these birds to Southwest communities prior to the 13th century, said Richard George, graduate student in anthropology, Penn State.Historically, scarlet macaws lived from South America to eastern coastal Mexico and Guatemala, thousands of miles from the American Southwest. Previously, researchers thought that ancestral Puebloan people might have traveled to these natural breeding areas and brought birds back, but the logistics of transporting adolescent birds are difficult. None of the sites where these early macaw remains were found contained evidence of breeding -- eggshells, pens or perches."We were interested in the prehistoric scarlet macaw population history and the impacts of human direct management," said George. "Especially any evidence for directed breeding or changes in the genetic diversity that could co-occur with different trade networks."The researchers sequenced the mitochondrial DNA of 20 scarlet macaw specimens, but were only able to obtain full sequences from 14. They then directly radiocarbon-dated all 14 birds with complete or near complete genomes and found they fell between 900 and 1200 CE."We looked at the full mitochondrial genome of over 16,000 base pairs to understand the maternal relationships represented in the Chaco Canyon and Mimbres regions," said George.Mitochondrial DNA exists separate from the cell nucleus and is inherited directly from the mother. While nuclear DNA combines the DNA inherited from both parents, mitochondrial DNA can show direct lineage because all siblings have the same mtDNA as their mother, and she has the same mtDNA as her own siblings and mother, all the way back through their ancestry.Scarlet macaws in Mexico and Central America have five haplogroups -- genetically similar, but not identical mitochondrial DNA lines -- and each haplogroup has a number of haplotypes containing identical DNA lines. The researchers found that their scarlet macaws were all from haplogroup 6 and that 71 percent of the birds shared one of four unique haplotypes. They report the results of this analysis today (Aug 13) in the The researchers found that the probability of obtaining 14 birds from the wild and having them all come from the same haplogroup, one that is small and isolated, was extremely small. A better explanation, especially because these specimens ranged over a 300-year period, is that all the birds came from the same breeding population and that this population existed somewhere in the American Southwest or northern Mexico."These birds all likely came from the same source, but we don't have any way to support that assumption without examining the full genome," said George. "However, the genetic results likely indicate some type of narrow breeding from a small founder population with little or no introgression or resupply."However, no one has found macaw breeding evidence dating to the 900 to 1200 period in the American Southwest or northern Mexico."The next step will be to analyze macaws from other archaeological sites in Arizona and northern Mexico to narrow down the location of this early breeding colony," said Douglas Kennett, professor and head of anthropology, Penn State, and co-director or the project.
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Genetically Modified
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August 13, 2018
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https://www.sciencedaily.com/releases/2018/08/180813133352.htm
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Thermal switch discovered in engineered squid-based biomaterials
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Tuning materials for optimal optical and electrical properties is becoming commonplace. Now, researchers and manufacturers may be able to tune materials for thermal conductivity by using a squid-inspired protein made of multiple DNA repeats.
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"Controlling thermal transport in modern technologies -- refrigeration, data storage, electronics or textiles -- is an unsolved problem," said Melik Demirel, professor of engineering science and mechanics and director, Center for Research on Advanced Fiber Technologies at Penn State. "For example, most standard plastic materials have very low thermal conductivity and they are thermal insulators. These squid-based bio-materials that we are working on have low conductivity at ambient humidity, but they can be engineered so that their thermal conductivity increases dramatically."In this case, the increase is dependent on how many tandem repeats are in the protein, and can be 4.5 times larger than increases seen in conventional plastics. Tandem repeats are repeating strings of DNA that are found in nature, in this case, in squid ring teeth.One potential use of this bioprotein film might be as a fabric coating, especially for athletic wear, said the researchers. The material could be perfectly comfortable and cozy in everyday use, but when actually used for heavy activity, the sweat produced by the wearer could "flip" the thermal switch and allow the fabric to remove heat from the wearer's body.Demirel and his team have designed synthetic proteins that are patterned on tandem repeating sequences. They are able to choose the number of repeats they want and investigate how the various proteins react, in this case, to moisture."Under ambient conditions -- less than 35 percent humidity -- the thermal conductivity of these proteinaceous films do not depend on repeat units or molecular weight, and demonstrate similar thermal conductivities to disordered polymers and water-insoluble proteins," the researchers report today (Aug. 13) in However, when the films are engineered to have higher molecular topology, the thermal conductivity jumps when they become wetter, through high humidity, water or sweat. In collaboration with the University of Virginia team and NIST, the researchers found that as the number of tandem repeats increased, the thermal conductivity did as well."Because the thermal conductivity when wet is linearly related to the number of repeats, we can program the amount of thermal conductivity into the material," said Demirel. "So, we could make better thermal switches, regulators and diodes similar to high-performance devices to solve the problems in modern technologies such as refrigeration, data storage, electronics or textiles."When the material returns to normal ambient humidity or lower, the switch turns off, and the protein no longer conducts heat as efficiently.
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Genetically Modified
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August 9, 2018
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https://www.sciencedaily.com/releases/2018/08/180809141144.htm
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Recording every cell's history in real-time with evolving genetic barcodes
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All humans begin life as a single cell that divides repeatedly to form two, then four, then eight cells, all the way up to the ~26 billion cells that make up a newborn. Tracing how and when those 26 billion cells arise from one zygote is the grand challenge of developmental biology, a field that has so far only been able to capture and analyze snapshots of the development process.
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Now, a new method developed by scientists at the Wyss Institute and Harvard Medical School (HMS) finally brings that daunting task into the realm of possibility using evolving genetic barcodes that actively record the process of cell division in developing mice, enabling the lineage of every cell in a mouse's body to be traced back to its single-celled origin.The research is published today in "Current lineage-tracking methods can only show snapshots in time, because you have to physically stop the development process to see how the cells look at each stage, almost like looking at individual frames of a motion picture," said senior author George Church, Ph.D., who is a Founding Core Faculty member at the Wyss Institute, Professor of Genetics at HMS, and Professor of Health Sciences and Technology at Harvard and MIT. "This barcode recording method allows us to reconstruct the complete history of every mature cell's development, which is like playing the full motion picture backwards in real-time."The genetic barcodes are created using a special type of DNA sequence that encodes a modified RNA molecule called a homing guide RNA (hgRNA), which was developed in a previous paper. hgRNA molecules are engineered such that when the enzyme Cas9 (of CRISPR-Cas9 fame) is present, the hgRNA will guide the Cas9 to its own hgRNA sequence in the genome, which Cas9 then cuts. When the cell repairs that cut, it can introduce genetic mutations in the hgRNA sequence, which accumulate over time to create a unique barcode.The researchers implemented the hgRNA-Cas9 system in mice by creating a "founder mouse" that had 60 different hgRNA sequences scattered throughout its genome. They then crossed the founder mouse with mice that expressed the Cas9 protein, producing zygotes whose hgRNA sequences started being cut and mutated shortly after fertilization."In every single cell that the zygote divides to become, there's a chance that its hgRNAs will mutate," explained first author Reza Kalhor, Ph.D., a postdoctoral research fellow at the Wyss Institute and HMS. "In each generation, all the cells acquire their own unique mutations in addition to the ones they inherit from their mother cell, so we can trace how closely related different cells are by comparing which mutations they have."Each hgRNA can produce hundreds of mutant alleles; collectively, they can generate a unique barcode that contains the full developmental lineage of each of the ~10 billion cells in an adult mouse.The ability to continuously record cells' development also allowed the researchers to resolve a longstanding question regarding the embryonic brain: does it distinguish its front from its back end first, or its left from its right side first? By comparing the hgRNA mutation barcodes present in cells taken from different parts of two mice's brains, they found that neurons from the left side of each brain region are more closely related to neurons from the right side of the same region than to neurons from the left side of neighboring regions. This result suggested that front-back brain patterning emerges before left-right patterning in the development of the central nervous system."This method allows us to take the final developmental stage of a model organism and from there reconstruct a full lineage tree all the way back to its single-cell stage. It's an ambitious goal that will certainly take many labs several years to realize, but this paper represents an important step in getting there," said Church. The researchers are now focusing on improving their readout techniques so that they can analyze the barcodes of individual cells and reconstruct the lineage tree that has been recorded."Being able to record cells continuously over time is a huge milestone in developmental biology that promises to exponentially increase our understanding of the process by which a single cell grows to form to an adult animal and, if applied to disease models, it could provide entirely new insights into how diseases, such as cancer, emerge," said Donald Ingber, M.D., Ph.D., Founding Director of the Wyss Institute who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at Harvard's John A. Paulson School of Engineering and Applied Sciences (SEAS).Additional authors of the paper include Kian Kalhor from Sharif University of Technology in Tehran, Iran; Leo Mejia from HMS, Kathleen Leeper and Amanda Graveline from the Wyss Institute, and Prashant Mali, Associate Professor at the University of California, San Diego.This research was supported by the National Institutes of Health and the Intelligence Advanced Research Projects Activity.
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Genetically Modified
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August 8, 2018
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https://www.sciencedaily.com/releases/2018/08/180808075309.htm
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Hijacking hormones for plant growth
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Hormones designed in the lab through a technique combining chemistry, biology, and engineering might be used to manipulate plant growth in numerous ways, according to a
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Scientists harnessed the power of synthetic chemistry to design compounds similar to auxin, a small chemical hormone that controls nearly all aspects of plant growth, development, and behavior.These compounds might be used for various agricultural purposes, for example for manipulating the ripening of fruit crops or for preventing the undesirable spread of transgenes (genes that have been transferred from one organism to another) in the field."It is truly gratifying as a plant biologist that collaboration with synthetic chemists could yield such a game-changing tool. With a new version of auxin and its engineered receptor, we could possibly pinpoint the desired auxin action in target plants or tissues of interest without disrupting the physiology of other plant parts or neighbors," said lead author Dr. Keiko Torii, of the University of Washington, in Seattle.
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Genetically Modified
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August 3, 2018
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https://www.sciencedaily.com/releases/2018/08/180803160207.htm
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Groundbreaking poplar study shows trees can be genetically engineered not to spread
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The largest field-based study of genetically modified forest trees ever conducted has demonstrated that genetic engineering can prevent new seedlings from establishing.
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The "containment traits" that Oregon State University researchers engineered in the study are important because of societal concerns over gene flow -- the spread of genetically engineered or exotic and invasive trees or their reproductive cells beyond the boundaries of plantations."There's still more to know and more research to be done, but this looks really good," said corresponding author Steve Strauss, distinguished professor of forest biotechnology at OSU. "It's very exciting."Findings from the study -- which looked at 3,300 poplar trees in a 9-acre tract over seven growing seasons -- were published today in Poplars are fast growing and the source of many products, from paper to pallets to plywood to frames for upholstered furniture.In trees like poplars that have female and male individuals, female flowers produce the seeds and male flowers make the pollen needed for fertilization.Strauss and colleagues in the Department of Forest Ecosystems and Society assessed a variety of approaches for making both genders of trees sterile, focusing on 13 genes involved in the making of flowers or controlling the onset of reproduction.Individually and in combination, the genes had their protein function or RNA expression modified with the goal of obtaining sterile flowers or a lack of flowering.The upshot: Scientists discovered modifications that prevented the trees from producing viable sexual propagules without affecting other traits, and did so reliably year after year. The studies focused on a female, early-flowering poplar that facilitates research, but the genes they targeted are known to affect both pollen and seed and thus should provide general approaches to containment.In addition to the findings, the research was notable for its scope, duration, and broad network of funders, both government and industry."I'm proud that we got the research done," Strauss said. "It took many years and many people doing it, managing it."People have this fear that GMO trees will take over the world, but these are containment genes that make taking over the world essentially impossible," he said. "If something is GMO, people assume it's dangerous -- it's guilty until proven safe in the minds of many and in our regulations today. In contrast, scientists say the focus should be on the trait and its value and safety, not the method used.At the start of the research, Strauss wondered if the trees would look normal or survive or express their new traits stably and reliably. All the answers were a strong yes."Will our trees be OK, will they be variable or unpredictable? The trees were fine," he said. "Year after year, the containment traits reliably worked where we got the genetics right. Not all of the constructs worked but that's why you do the research."Strauss also noted that newer genetic approaches in his laboratory, especially CRISPR-based gene editing, are making the production of reliably contained and improved trees even easier and more efficient.He pointed out that "the work focused on pollen and seeds, but poplar can also spread vegetatively -- for example by root sprouts. But those are far slower, much narrower in distance, and far easier to control in and around plantations."
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Genetically Modified
| 2,018 |
August 2, 2018
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https://www.sciencedaily.com/releases/2018/08/180802141744.htm
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How to make the gene-editing tool CRISPR work even better
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Among the most significant scientific advances in recent years are the discovery and development of new ways to genetically modify living things using a fast and affordable technology called CRISPR. Now scientists at The University of Texas at Austin say they've identified an easy upgrade for the technology that would lead to more accurate gene editing with increased safety that could open the door for gene editing safe enough for use in humans.
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The team of molecular biologists found conclusive evidence that Cas9, the most popular enzyme currently used in CRISPR gene editing and the first to be discovered, has less effectiveness and precision than one of the lesser-used CRISPR proteins, called Cas12a.Because Cas9 is more likely to edit the wrong part of a plant's or animal's genome, disrupting healthy functions, the scientists make the case that switching to Cas12a would lead to safer and more effective gene editing in their study published Aug. 2 in the journal "The overall goal is to find the best enzyme that nature gave us and then make it better still, rather than taking the first one that was discovered through historical accident," said Ilya Finkelstein, an assistant professor of molecular biosciences and a co-author of the study.Scientists are already using CRISPR, a natural mechanism used by bacteria to defend against viruses, to learn more about human genes, genetically modify plants and animals and develop such science-fiction-inspired advances as pigs that contain a fat-fighting mouse gene, leading to leaner bacon. Many expect CRISPR to lead to new treatments for human diseases and crops that have higher yield or resist droughts and pests.But the CRISPR systems found in nature sometimes target the wrong spot in a genome, which -- applied to humans -- could be disastrous, for example, failing to correct for a genetic disease and instead turning healthy cells into cancerous cells.Some previous studies have hinted that Cas12a is choosier than Cas9, but the research before now was inconclusive. This latest study, the researchers say, closes the case by showing that Cas12a is a more precise gene-editing scalpel than Cas9 and explaining why.The team, led by graduate student Isabel Strohkendl and professor Rick Russell, found that Cas12a is choosier because it binds like Velcro to a genomic target, whereas Cas9 binds to its target more like super glue. Each enzyme carries a short string of genetic code written in RNA that matches a target string of genetic code written in the DNA of a virus. When it bumps into some DNA, the enzyme starts trying to bind to it by forming base pairs -- starting at one end and working its way along, testing to see how well each letter on one side (the DNA) matches the adjacent letter on the other side (the RNA).For Cas9, each base pair sticks together tightly, like a dab of super glue. If the first few letters on each side match well, then Cas9 is already strongly bound to the DNA. In other words, Cas9 pays attention to the first seven or eight letters in the genomic target, but pays less attention as the process goes on, meaning it can easily overlook a mismatch later in the process that would lead it to edit the wrong part of the genome.For Cas12a, it's more like a Velcro strap. At each point along the way, the bonds are relatively weak. It takes a good match all along the strip for the two sides to hold together long enough to make an edit. That makes it much more likely that it will edit only the intended part of the genome."It makes the process of base-pair formation more reversible," Russell said. "In other words, Cas12a does a better job of checking each base pair before moving on to the next one. After seven or eight letters, Cas9 stops checking, whereas Cas12a keeps on checking out to about 18 letters."The researchers said that Cas12a still isn't perfect, but the study also suggests ways that Cas12a can be improved further, perhaps one day realizing the dream of creating a "precision scalpel," an essentially error-proof gene-editing tool."On the whole, Cas12a is better, but there were some areas where Cas12a was still surprisingly blind to some mispairing between its RNA and the genomic target," Finkelstein said. "So what our work does is show a clear path forward for improving Cas12a further."The researchers are currently using these insights in a follow-on project designed to engineer an improved Cas12a.The study's other co-authors are graduate student James Rybarski and former undergraduate student Fatema Saifuddin.This work was supported by grants from the National Institute of General Medical Sciences and the Welch Foundation.
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Genetically Modified
| 2,018 |
August 1, 2018
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https://www.sciencedaily.com/releases/2018/08/180801160017.htm
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Yeast grow -- but can't always breed -- with their 16 chromosomes fused into two
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Baker's yeast survive and grow after a drastic reorganization, not of their genes, but of the chromosome superstructures that house, protect and control access to their DNA code, a study just published in
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Led by NYU School of Medicine, a research team fused together chromosomes in stages until the 6,000 genes in a species of one-celled fungus, Engineering such "reproductive isolation" between yeast strains would be a must to achieve certain hoped-for, future applications of yeast -- like recycling agricultural waste to make fuel, or fighting starvation by supplementing livestock feed, say the study authors. Such endeavors would require the creation of strains that could be released into the field, but that were incapable of mating with naturally occurring yeast to alter ecosystems.Further in the future, a better understanding of how chromosomes are copied and apportioned in sex cells -- spores in yeast; eggs and sperm in humans -- may suggest ways to counter errors that cause too short, too long, missing or extra chromosomes to be passed down in human cells. Such events are a main cause of miscarriages and mental retardation, including Down's syndrome, in which an embryo receives an extra copy of the 21st human chromosome. Yeast chromosomes are similar enough to human ones to make good models for study."We found that yeast can tolerate drastic changes in chromosome number without disrupting the action of the genes in them, more evidence of their robustness as an engineering platform," says senior study author Jef Boeke, PhD, director of the Institute for Systems Genetics at NYU Langone Health. "Beyond applications, this work sheds light on the wild trajectory of accidental chromosome duplications and fusions across evolution that has left one ant species with a single pair of chromosomes, humans with 23 pairs, and one species of butterfly with 220. We are learning how one species becomes two."The study results concern chromosomes, large protein bundles that, upon receiving the right signals, unwind to expose for reading by the cellular machinery just the bits of DNA instructions needed for the jobs at hand in each cell type. All chromosomes unwind when it is time to copy the entire genetic code before cell division, where one cell becomes two. Such divisions either create more genetically identical cells during growth (mitosis), or further divide a parental cell's chromosomes in rounds (meiosis) that yield sex cells, which can then combine with other sex cells to create new organisms.As cells get ready to divide such that each resulting cell gets its proper share of DNA, the newly copied chromosomes are connected by special DNA sets called centromeres, creating pairs with four chromosome "arms." Each arm is capped by DNA sets called telomeres which protect against enzymes that would otherwise damage the exposed tips.The current study authors used the famous CRISPR-Cas9 gene editing technology to cut 14 centromeres and 28 telomeres out of the complete set of yeast chromosomes (the genome). Without these telomeres or centromeres in place, the remaining DNA chains fused in steps until only two remained, each containing roughly half the genetic material for the Interestingly, the team was unable to generate a living strain of yeast with just one chromosome pair housing all of its genes. The authors say this may be because the two large chromosomes operating in the new strain had arms that, at about 5.9 million DNA molecular letters (bases) each, approached the maximum length limit. Longer than that and an arm is likely to have its end clipped off as a cell divides.Remarkably, the researchers found that yeast with chromosomes that are up to four times the maximum size of those seen in nature survived, divided and multiplied (grew) via mitosis at roughly the same rates as natural strains.However, when the team took the offspring from crosses of yeast strains with different chromosome numbers, and then induced the offspring of the crosses to make sex cells via meiosis, the ability to produce viable spores dropped in this next generation as the difference grew between the chromosome numbers of their parents. The team surmises that this is because chromosomes within such sex cells no longer lined up so that the DNA could be divided properly during cell division, leaving some with lethal DNA dosage abnormalities.Experiments showed that a difference in chromosome number of eight, say after eight fusions, was enough to keep an engineered strain from interbreeding with its ancestral species, achieving the reproductive isolation so important to envisioned applications. When two members of a species can no longer interbreed, they can no longer mix DNA and accumulate different genetic changes over time. This begins the process of their becoming different species, says Boeke.Along with Boeke, authors of the current study were Jingchuan Luo and Xiaoji Sun in the Institute for Systems Genetics at NYU Langone Health, along with Brendan Cormack in the Department of Molecular Biology & Genetics at Johns Hopkins University School of Medicine. The work was supported by National Science Foundation grant MCB-1616111.
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Genetically Modified
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July 31, 2018
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https://www.sciencedaily.com/releases/2018/07/180731103946.htm
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Gene therapy: Better adenine base editing system
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Two research teams from East China Normal University and Sun Yat-Sen University in China have developed and improved the ABE system in mouse and rat strains, which has great implications for human genetic disorders and gene therapy. The research has been published by Springer Nature in two articles in the open access journal
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The human gene is composed of the bases Adenine (A), Thymine (T), Cytosine (C) and Guanine (G), which are arranged in a particular order to encode genetic information. The ABE system is able to generate a desired Adenine (A) to Guanine (G) conversion and therefore allows scientists to alter genetic codes with minimal undesired outcomes. Since almost half of human genetic diseases are caused by C/G to T/C mutation, which could be ideally corrected through ABE, this is a promising technology for therapeutic applications.Mice and rats are two of the most critical model organisms for biological and medical studies because they can be easily bred and are physiologically similar to humans. Using genetically modified rodent models scientists have made significant progress in understanding human biology, disease pathology and the development of therapeutics for numerous diseases. However, it is not easy to generate mouse or rat strains containing point mutants identified in human diseases, even with targeted genome editing like CRISPR/Cas9.In these studies, the researchers used the ABE system to efficiently generate three mice strains to mimic the genetic muscle degeneration disorder called Dunchenne Muscular Dystrophy (DMD). They also used a rat model to mimic the hereditary glycogen storage disease type II known as GSD?or Pompe disease. These models could be an important resource for testing innovative therapeutics, especially gene therapy."It is critical to expand the targeting scope of the ABE system and test its efficiency and editing window in cells and animals," says Dali Li.His group at East China Normal University has enabled targeting of genomic sites that were not covered by the original ABE system. They used chemically modified "guide RNAs" (gRNAs) to enhance the overall editing efficiency."The early results are promising," Li says. "We are working hard to apply this powerful tool in preclinical therapeutic studies to develop novel gene therapy strategies for different human genetic disorders. I believe that clinical application will be in the near future, although the improvement of overall efficiency and the delivery system for ABE is a challenge."
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Genetically Modified
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July 24, 2018
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https://www.sciencedaily.com/releases/2018/07/180724193644.htm
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Rice with fewer stomata requires less water and is better suited for climate change
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Rice plants engineered to have fewer stomata -- tiny openings used for gas exchange -- are more tolerant to drought and resilient to future climate change, a new study has revealed.
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Scientists from the University of Sheffield have discovered that engineering a high-yielding rice cultivar to have reduced stomatal density, helps the crop to conserve water and to survive high temperatures and drought.Much of humanity relies on rice as a food source, but rice cultivation is particularly water intensive -- using an estimated 2,500 litres of water per kilogram of rice produced.However, almost half of the global rice crop derives from rain-fed agricultural systems where drought and high temperatures are predicted to become more frequent and damaging under climate change.Like most plants, rice uses microscopic pores called stomata to regulate carbon dioxide uptake for photosynthesis, along with the release of water vapour via transpiration. When water is plentiful, stomatal opening also permits regulation of plant temperature by evaporative cooling. Under water-limiting drought conditions, stomatal closure normally slows down water loss. Low stomatal density rice conserves its water better under drought, and so has more water left to cool itself when necessary.Dr Robert Caine, Research Associate from the University of Sheffield's Department of Molecular Biology and Biotechnology and Principal Investigator of the study, said: "Future predicted decreases in water availability, combined with increased frequency of extreme drought and high temperature events, are likely to present particular challenges for farmers -- resulting in substantial crop loss."Our study has shown that rice plants with fewer stomata are drought tolerant and more conservative in their water use. This means they should perform better in the future under climate change conditions."We found that the engineered rice crops gave equivalent or even improved yields, which means it could have a massive impact on our future food security which is threatened by climate change."The new study, published in When grown at elevated atmospheric carbon dioxide levels, the low stomatal density rice plants were able to survive drought and high temperature (40 degrees Celsius) for longer than unaltered plants.Julie Gray, Professor of Plant Molecular Biology and lead author of the study, said: "Stomata help plants to regulate their water use, so this study could have a significant impact on other crops which are at risk under climate change."At the University of Sheffield we believe in a sustainable future and work towards solutions to the most pressing global challenges."This study was conducted at the University of Sheffield's centre of excellence for translational plant and soil science called P3 (Plant Production and Protection).P3 encompasses the breadth of plant and soil expertise at Sheffield and capitalises on the unparalleled ability to work across biological scales, from genome to the global atmosphere.
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Genetically Modified
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July 19, 2018
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https://www.sciencedaily.com/releases/2018/07/180719142113.htm
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How plant breeding technologies could make fruits and vegetables more exciting to eat
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Forget vegetables with dull colors and fuzzy skin or fruits that lack of flavor -- the produce aisle of the future could offer plant products that are designed for creative cooks and fussy eaters. In a review article published July 19 in the journal
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"Novelty drives a lot of first time purchasing," says Andrew Allan of New Zealand science institute Plant & Food Research, who co-wrote the article with Richard Espley. "If the experience is good, then the consumer will purchase again. Choice is key -- there is no risk with more choice."In their review, the authors describe how fast breeding with CRISPR-Cas9 gene editing doesn't rely on the addition of a new DNA sequence as is often the case with other genetically modified crops. Rather, these breeding technologies allow scientists to edit existing genes, particularly transcription factor genes called MYBs, which control many of a plant's key consumer traits. Information from these experiments can also be used to inform selection criteria in conventional breeding programs."MYBs often regulate the compounds that generate a fruit or vegetables' 'wow' factor -- its color," Allan says. "These compounds are also associated with important health benefits such as lowering cardiovascular disease or acting as vitamins. By using MYBs to elevate these compounds to create a richer color, we can make produce both more appealing to consumers and more beneficial for the human diet."This works for changes below the surface, as well. For example, apples and potatoes have colorless flesh, which often means that nutrients are concentrated in the skin. By altering MYBs to produce higher quantities of compounds in the flesh of the apple or potato, scientists can create fruits and vegetables where every bite has the same concentration of vitamins.The technology is also being used to adjust flavor and texture, and Allan is excited by what this progress could mean for the future of our supermarkets. He even suggests that this could usher in "the next green revolution, with more product choice for developed countries, greater yields for less developed countries, and more growing options for climate resilience." To those who may have reservations, he says new breeding techniques emulate changes to DNA made in nature and can be used to advance conventional breeding and growing practices.The authors receive support from the New Zealand Government, Ministry of Business, Innovation and Employment Endeavour Funds, 'Turbo Breeding' and 'Filling the Void.'
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Genetically Modified
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June 29, 2018
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https://www.sciencedaily.com/releases/2018/06/180629114703.htm
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Timing is key for bacteria surviving antibiotics
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For bacteria facing a dose of antibiotics, timing might be the key to evading destruction. In a series of experiments, Princeton researchers found that cells that repaired DNA damaged by antibiotics before resuming growth had a much better chance of surviving treatment.
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When antibiotics hit a population of bacteria, often a small fraction of "persister" cells survive to pose a threat of recurrent infection. Unlike bacteria with genetic resistance to antibiotics, evidence suggests that persisters stay alive in part by stalling cellular processes targeted by the drugs.In a new study, Princeton researchers examined a class of antibiotics that target bacterial DNA. In bacterial populations, some cells repair damaged DNA before resuming growth, and others resume growth before making repairs. The researchers found that those that make repairs before resuming growth generally are the ones that survive as persisters. The research advances a long-term goal to make antibiotic treatment more effective.In results published June 18 in the "But that doesn't guarantee that they're necessarily going to survive," said Mok. "We hypothesized that the timing of DNA repair and the resumption of growth-related activities like DNA synthesis could impact the survival of persisters after treatment."To test this hypothesis, Mok and Brynildsen used a strain of These non-growing cells, they found, experienced DNA damage similar to growing cells treated with ofloxacin. However, the non-growing cells showed delays in resuming DNA synthesis and repair following treatment.By controlling the activity of a key DNA repair protein, RecA, the researchers tested the effect of further delaying DNA repair until after the resumption of DNA synthesis. This led to a sevenfold decrease in survival compared to cells that continuously produced RecA, demonstrating that persistence to ofloxacin depends on repairing DNA damage before synthesizing the new DNA necessary for growth.Mok and Brynildsen then examined persistence in normal cells placed in a low-nutrient environment to stall their growth, simulating a condition that bacteria frequently encounter within an infected host. Indeed, following ofloxacin treatment, if cells were starved of carbon sources for at least three hours, they observed nearly complete tolerance to the antibiotic. This tolerance depended on effective DNA repair processes. They also observed enhanced persistence toward ofloxacin with nutrient deprivation after treatment among cells growing in biofilms, which are groups of bacteria that stick to surfaces and are implicated in a majority of hospital-treated bacterial infections.Jan Michiels, a professor of microbiology at the University of Leuven-VIB in Belgium, said the study used "an elegant model system" to probe the underlying mechanisms of persistence. Michiels, who was not involved in the research, said it represents "a landmark discovery providing new fundamental insights into how persister cells avoid death."Ofloxacin and other similar antibiotics are included on the World Health Organization's Model List of Essential Medicines, a catalog of the most important drugs for meeting health care needs. Curbing bacterial persistence could be a promising route to making these therapies more effective against urinary tract infections, staph infections and other bacterial diseases."Nutrient starvation is a stress that bacteria can routinely encounter at an infection site," said Mok. "Our results suggest that in the period after antibiotic treatment we can consider looking at targeting some of these DNA repair processes, and see whether that can improve treatment outcome." One counterintuitive approach might be to speed up bacterial growth following antibiotic treatment, thereby dooming the cells to outpace their repair mechanisms and die. However, the researchers added that other approaches would likely be better than fostering the growth of a pathogen in a patient.Brynildsen's group and others are interested in finding potential drug compounds that may interfere with bacterial DNA repair, as well as examining the relationship between antibiotic tolerance and genetic resistance.
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Genetically Modified
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June 27, 2018
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https://www.sciencedaily.com/releases/2018/06/180627160520.htm
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Mandatory labels reduce GMO food fears
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As the U.S. Department of Agriculture prepares guidelines for labeling products that contain genetically modified ingredients, a new study from the University of Vermont reveals that a simple disclosure can improve consumer attitudes toward GMO food.
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Led by Jane Kolodinsky, an applied economist in UVM's College of Agriculture and Life Sciences, the study compared levels of consumer opposition to GMO foods in Vermont -- the only U.S. state to have implemented a mandatory labeling policy -- with consumer attitudes in the rest of the U.S. The analysis showed opposition to GMO food fell by 19% in Vermont after the implementation of mandatory labels.The study is the first to examine the real-world impact of consumer attitudes toward GMO foods in a state where consumers were exposed to mandatory GMO labels."Our findings put to bed the idea that GMO labels will be seen as a warning label," said Kolodinsky, professor and chair of the Department of Community Development and Applied Economics and a Fellow of UVM's Gund Institute for the Environment. "What we're seeing is that simple disclosures, like the ones implemented in Vermont, are not going to scare people away from these products."Published today in Several studies, including past research by Kolodinsky, show consumers consistently express a desire for labels on GMO foods, but mandatory labeling has been opposed by some manufacturers and scientific organizations for fear that the labels would be perceived as warning signs and might signal that a product is unsafe or harmful to the environment.Despite numerous scientific studies that have shown that GMO foods are safe, nationwide, the majority of consumers express opposition to the use of GMO technologies, a trend that has been steadily increasing over the past decade."We're finding that both in real-world and hypothetical studies, the introduction of a simple disclosure label can actually improve consumer attitudes toward these technologies. In a state that has been such a hot bed for GMO opposition, to see this change is striking," said Kolodinsky, who has tracked attitudes to GMOs in Vermont since 2003.Kolodinsky's latest study, with co-author Jayson Lusk of Purdue University's Department of Agricultural Economics, suggests a simple, straightforward label disclosing whether a product is "produced or partially produced using GMO ingredients" may improve consumer confidence in GMO technologies and enable consumers to make an informed decision.However, proposed national labeling regulations released by the U.S. Department of Agriculture in May, seek a narrower definition of genetic engineering and propose alternatives to simple labeling disclosures. The draft guidelines also propose changing the labeling terminology from GMO to "bioengineered" or "BE," a new descriptor for genetic engineering that is unfamiliar to most of the general public.The USDA has invited public comments on the draft guidance through July 3, 2018.While several states introduced bills to require labeling of GMO foods, Vermont became the first and only U.S. state to implement a mandatory labeling initiative in July 2016 before the new federal legislation came into effect.Kolodinsky, who collected data on Vermonters' attitudes toward GMO food before and after the labeling policy was implemented, combined her results with Lusk's national data. Taken together, the study analyzed attitudes of over 7,800 consumers from 2014-2017 who ranked their attitude toward GMO food using a one to five scale. When controlling for demographic factors, opposition to genetic engineering fell significantly in Vermont after mandatory labeling, whereas opposition continued to increase nationwide."One of the concerns many people, including myself, expressed about mandating GMO labels is that consumers might see the label as a type of warning signal and increase aversion to the label. This research shows that this particular concern about mandatory GMO labels is likely misplaced," said co-author Lusk.Kolodinsky and Lusk note the findings are consistent with prior research that suggest "labels give consumers a sense of control, which has been shown to be related to risk perception." Indeed, some food manufacturers, including General Mills and Campbells, continue to voluntarily label GMO food products citing consumer demand for transparency.
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Genetically Modified
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June 27, 2018
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https://www.sciencedaily.com/releases/2018/06/180627160514.htm
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Genetically humanized mice could boost fight against aggressive hepatitis
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Hepatitis delta virus (HDV) causes the most aggressive form of viral hepatitis in humans, putting at least 20 million people worldwide at risk of developing liver fibrosis, cirrhosis, and liver cancer. Efforts to develop effective treatments against HDV have been hampered by the fact that laboratory mice are not susceptible to the virus. But, in a study published June 27, 2018, in the journal
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HDV is a small, RNA-based "satellite" virus that produces just a single protein of its own and therefore requires additional proteins provided by another liver virus, hepatitis B virus (HBV). HDV can infect patients already carrying HBV, or both viruses can infect patients simultaneously. Though infections can be prevented with an anti-HBV vaccine, there are no antiviral therapies available to cure existing HDV infections.HDV and HBV infect the liver by binding to a protein called NTCP that is present on the surface of liver cells. But the viruses only recognize the version of NTCP present in humans and a few other primates, and therefore can't infect mice or other small mammals that produce their own versions of NTCP. This has made it difficult to study HBV and HDV infections in the laboratory. Researchers have tried transplanting human liver cells into immunocompromised mice before infecting them with virus, but this approach has produced inconsistent results and is both expensive and time-consuming.Ploss and colleagues, led by graduate student Benjamin Winer, took a different approach. They generated mice that express the human NTCP protein in their liver cells, allowing these cells to be infected by HBV and HDV.In these mice, HBV failed to replicate after entering mouse liver cells but HDV was able to establish persistent infection when provided with the HBV proteins it needs to propagate. For example, mice genetically engineered to produce both human NTCP and the entire HBV genome could be infected with HDV for up to 14 days. "To our knowledge, this is the first time the entire HDV life cycle has been recapitulated in a mouse model with inheritable susceptibility to HDV," Ploss said.The mice were able to rid themselves of HDV before they developed any liver damage, apparently by mounting an immune response involving antiviral interferon proteins and various white blood cell types, including Natural Killer (NK) cells and T cells. Accordingly, mice expressing human NTCP and the HBV genome, but lacking functional B, T, and NK cells could be infected with HDV for two months or more.These immunocompromised animals allowed Ploss and colleagues to test the effectiveness of two drugs that are currently being developed as treatments for HDV infection. Both drugs -- either alone or in combination -- suppressed the levels of HDV in immunocompromised mice after viral infection. But the drugs were not able to completely clear the mice of HDV; viral levels rose again within weeks of stopping treatment."This is largely in line with recently reported data from clinical trials, showing the utility of our model for preclinical antiviral drug testing," Winer said."Our model is amenable to genetic manipulations, robust, and can be adopted as a method to rapidly screen for potential treatments," Ploss added.Timothy M. Block, president of the Hepatitis B Foundation and its Baruch S. Blumberg Institute, who was not involved in the study, said "These systems should be able to provide practical, and presumably economical tools. Their work is urgently needed, and a desperate community welcomes it. I emphasize that it is often the new methods in science that revolutionize a field such as drug discovery, almost as much as the new drugs themselves."
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Genetically Modified
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June 20, 2018
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https://www.sciencedaily.com/releases/2018/06/180620162427.htm
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Rewiring plant defense genes to reduce crop waste
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Plants can be genetically rewired to resist the devastating effects of disease -- significantly reducing crop waste worldwide -- according to new research into synthetic biology by the University of Warwick.
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Led by Professor Declan Bates from the Warwick Integrative Synthetic Biology Centre (WISB) and Professor Katherine Denby from the University of York, who is also an Associate member of WISB, researchers have developed a genetic control system that would enable plants to strengthen their defence response against deadly pathogens -- so they could remain healthy and productive.When pathogens attack crop plants, they obtain energy and nutrients from the plant but also target the plant's immune response, weakening defence, and making the plants more vulnerable.Building on experimental data generated by Prof. Denby, Professor Bates' group simulated a pathogen attack in Arabidopsis plants, and modelled a way to rewire the plants' gene network, creating a defensive feedback control system to combat disease -- which works in much the same way as an aircraft autopilot.Just as an aircraft's autopilot control system detects disturbances like wind gusts or turbulence and acts to reject them, this new plant control system detects a pathogen attack, and prevents the pathogen weakening the plants' defence response.This method could render crops more resilient against disease, helping mitigate crop wastage throughout the world. Since the system can be implemented by re-wiring plants' natural defence mechanisms, no external genetic circuitry needs to be added.Declan Bates, Professor of Bioengineering at the University of Warwick's School of Engineering, commented:"Disease, drought and extreme temperatures cause significant yield losses in crop plants all over the globe, threatening world food security. It is therefore crucial to explore new ways to develop crops that are resilient to pathogen attacks and can maintain yields in challenging environments. This study shows the enormous potential of using feedback control to strengthen plants' natural defence mechanisms."Katherine Denby, Professor of Sustainable Crop Production and Director of the N8 AgriFood Resilience Programme at the University of York commented:"Minimising crop waste is obviously an essential part of creating a more sustainable food system. What is exciting here is applying engineering principles to plant biology to predict how to re-design plant gene regulation to enhance disease resistance. We use re-wiring of existing genes in the plant to prevent pathogen manipulation."The next steps of the research will be to take the theory into the lab, and experimentally implement the defensive feedback control system in plants.
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Genetically Modified
| 2,018 |
June 18, 2018
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https://www.sciencedaily.com/releases/2018/06/180618222442.htm
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360 degrees, 180 seconds: Technique speeds analysis of crop traits
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A potted nine-leaf corn plant sits on a Frisbee-sized plate. The tandem begins rotating like the centerpiece atop a giant music box, three degrees per second, and after two minutes the plant has pirouetted to its original position.
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Another minute passes, and on a nearby screen appears a digital 3-D image in the palette of Dr. Seuss: magenta and teal and yellow, each leaf rendered in a different hue but nearly identical to its actual counterpart in shape, size and angle.That rendering and its associated data come courtesy of LiDAR, a technology that fires pulsed laser light at a surface and measures the time it takes for those pulses to reflect back -- the greater the delay, the greater the distance. By scanning a plant throughout its rotation, this 360-degree LiDAR technique can collect millions of 3-D coordinates that a sophisticated algorithm then clusters and digitally molds into the components of the plant: leaves, stalks, ears.The University of Nebraska-Lincoln's Yufeng Ge, Suresh Thapa and their colleagues have devised the approach as a way to automatically and efficiently gather data about a plant's phenotype: the physical traits that emerge from its genetic code. The faster and more accurately phenotypic data can be collected, the more easily researchers can compare crops that have been bred or genetically engineered for specific traits -- ideally those that help produce more food.Accelerating that effort is especially important, the researchers said, to meet the food demands of a global population expected to grow from about 7.5 billion people today to nearly 10 billion in 2050."We can already do DNA sequencing and genomic research very rapidly," said Ge, assistant professor of biological systems engineering. "To use that information more effectively, you have to pair it with phenotyping data. That will allow you to go back and investigate the genetic information more closely. But that is now (reaching) a bottleneck, because we can't do that as fast as we want at a low cost."At three minutes per plant, the team's set-up operates substantially faster than most other phenotyping techniques, Ge said. But speed matters little without accuracy, so the team also used the system to estimate four traits of corn and sorghum plants. The first two traits -- the surface area of individual leaves and all leaves on a plant -- help determine how much energy-producing photosynthesis the plant can perform. The other two -- the angle at which leaves protrude from a stalk and how much those angles vary within a plant -- influence both photosynthesis and how densely a crop can be planted in a field.Comparing the system's estimates with careful measurements of the corn and sorghum plants revealed promising results: 91 percent agreement on the surface area of individual leaves and 95 percent on total leaf area. The accuracy of angular estimates was generally lower but still ranged from 72 percent to 90 percent, depending on the variable and type of plant.To date, the most common form of 3-D phenotyping has relied on stereo-vision: two cameras that simultaneously capture images of a plant and merge their perspectives into an approximation of 3-D by identifying the same points from both images.Though imaging has revolutionized phenotyping in many ways, it does have shortcomings. The shortest, Ge said, is an inevitable loss of spatial information during the translation from 3-D to 2-D, especially when one part of a plant blocks a camera's view of another part."It has been particularly challenging for traits like leaf area and leaf angle, because the image does not preserve those traits very well," Ge said.The 360-degree LiDAR approach contends with fewer of those issues, the researchers said, and demands fewer computational resources when constructing a 3-D image from its data."LiDAR is advantageous in terms of the throughput and speed and in terms of accuracy and resolution," said Thapa, doctoral student in biological systems engineering. "And it's becoming more economical (than before)."Going forward, the team wants to introduce lasers of different colors to its LiDAR set-up. The way a plant reflects those additional lasers will help indicate how it uptakes water and nitrogen -- the essentials of plant growth -- and produces the chlorophyll necessary for photosynthesis."If we can tackle those three (variables) on the chemical side and these other four (variables) on the morphological side, and then combine them, we'll have seven properties that we can measure simultaneously," Ge said. "Then I will be really happy."
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Genetically Modified
| 2,018 |
June 15, 2018
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https://www.sciencedaily.com/releases/2018/06/180615185415.htm
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Genetic engineering researcher: Politicians are deaf to people's ethical concerns
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While a many Danes question whether genetically modified foods are unnatural, this concern is much less apparent among politicians, according to Professor Jesper Lassen at the University of Copenhagen's Department of Food and Resource Economics. Lassen has investigated Danish attitudes about genetically modified foods since the early 90's.
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His most recent research has demonstrated that there is little or no correlation between the general public's reservations about genetically modified foods and what Danish politicians bring up for parliamentary debate."That people do not like genetically engineered foods is etched in stone. And, one of the main arguments is that they are perceived as unnatural. However, the question of perceived naturalness is never raised in Danish parliamentary debate. Politicians should never resort to populism and placate voters. They should take the public seriously and consider their arguments," he says.His study looks at parliamentary debate about EU legislation that addresses genetic engineering, and compares this with studies of public perceptions of genetically modified foods."There is an obvious disconnect between public concerns and how politicians debate genetically modified foods. There are numerous indications that elected officials live in a political bubble, where certain types of risk v. benefit arguments are important, while arguments about naturalness, for example, which are of important for the population, are never advanced," says Jesper Lassen.Jesper Lassen elaborates that there is skepticism among Danes and other Europeans about genetically modified foods with regards to whether they are ethically and morally sound."While questions of risks and benefits are important for people, so are the moral and ethical dimensions. In relation to genetically modified foods, for example, the concern is whether something is unnatural in such a way that it transcends species barriers or creates new types of organisms. These concerns overshadow all other reservations and serve as a moral veto," he says. In his analysis of the political debates, Jesper Lassen concluded that politicians are far more focused on the benefits and risks of genetically modified foods."For example, politicians discuss genetic engineering technology as a source of more robust crops, and whether the cultivation of genetically modified crops affects organic agriculture, or potential long-term environmental risks. In doing so, they ignore the ethical issues, which is what people care about most," emphasizes Jesper Lassen.
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Genetically Modified
| 2,018 |
June 14, 2018
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https://www.sciencedaily.com/releases/2018/06/180614213729.htm
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Non-coding DNA changes the genitals you're born with
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Male mice grow ovaries instead of testes if they are missing a small region of DNA that doesn't contain any genes, finds a new paper published in
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The study, led by researchers at the Francis Crick Institute, could help explain disorders of sex development in humans, at least half of which have an unknown genetic cause.Mammals will develop ovaries and become females unless the early sex organs have enough of a protein called The amount of Only 2% of human DNA contains the 'code' to produce proteins, key building blocks of life. The remaining 98% is 'non-coding' and was once thought to be unnecessary 'junk' DNA, but there is increasing evidence that it can play important roles.The latest study adds to this evidence, showing that a small piece of DNA called enhancer 13 (Enh13), located over half a million bases away from the Enh13 is located in part of the mouse genome that maps directly onto a region of the human genome. People with XY chromosomes who are missing a larger DNA fragment in this region of the genome develop female sex organs, and this study could finally explain why this happens.Experiments leading to sex reversal in mice are not new. In 1991, a team of scientists including Crick Group Leader Robin Lovell-Badge unveiled 'Randy' a chromosomally female (XX) mouse who developed as a male after the team introduced the "We've come a long way since Randy, and now for the first time we've demonstrated sex reversal after changing a non-coding region of DNA rather than a protein-coding gene," explains Professor Robin-Lovell Badge, senior author of the paper. "We think Enh13 is probably relevant to human disorders of sex development and could potentially be used to help diagnose some of these cases."Dr Nitzan Gonen, first author of the paper and postdoc at the Crick, says: "Typically, lots of enhancer regions work together to boost gene expression, with no one enhancer having a massive effect. We identified four enhancers in our study but were really surprised to find that a single enhancer by itself was capable of controlling something as significant as sex.""Our study also highlights the important role of what some still refer to as 'junk' DNA, which makes up 98% of our genome. If a single enhancer can have this impact on sex determination, other non-coding regions might have similarly drastic effects. For decades, researchers have looked for genes that cause disorders of sex development but we haven't been able to find the genetic cause for over half of them. Our latest study suggests that many answers could lie in the non-coding regions, which we will now investigate further.""We know that
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Genetically Modified
| 2,018 |
June 4, 2018
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https://www.sciencedaily.com/releases/2018/06/180604111912.htm
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A change in bacteria's genetic code holds promise of longer-lasting drugs
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By altering the genetic code in bacteria, researchers at The University of Texas at Austin have demonstrated a method to make therapeutic proteins more stable, an advance that would improve the drugs' effectiveness and convenience, leading to smaller and less frequent doses of medicine, lower health care costs and fewer side effects for patients with cancer and other diseases.
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The results were published today in the journal Many drugs commonly used to treat cancer and diseases of the immune system -- including insulin, human growth hormone, interferon and monoclonal antibodies -- can have a short active life span in the human body. That's because these drugs, which are proteins or chains of amino acids linked together by chemical bonds, contain the amino acid cysteine, which makes chemical bonds that break down in the presence of certain compounds found in human cells and blood.The new method replaces cysteine with another amino acid called selenocysteine, which forms hardier chemical bonds. The change would lead to drugs that have the same therapeutic benefit but increased stability and may survive longer in the body, according to the new study."We have been able to expand the genetic code to make new, biomedically relevant proteins," said Andrew Ellington, associate director of the Center for Systems and Synthetic Biology and a professor of molecular biosciences who co-authored the study.Biochemists have long used genetically modified bacteria as factories to produce therapeutic proteins. However, bacteria have built-in limitations that previously prevented harnessing selenocysteine in these therapies. Through a combination of genetic engineering and directed evolution -- whereby bacteria that produce a novel protein containing selenocysteine can grow better than those that don't -- the researchers were able to reprogram a bacteria's basic biology."We have adapted the bacteria's natural process for inserting selenocysteine to remove all the limitations, allowing us to recode any position in any protein as a selenocysteine," said Ross Thyer, a postdoctoral researcher in Ellington's lab who led the study.Other authors on the paper, all from UT Austin, are Raghav Shroff, Dustin Klein, Simon d'Oelsnitz, Victoria Cotham, Michelle Byrom and Jennifer Brodbelt.Thyer, Brodbelt and Ellington described the basic method in a paper in the Journal of the American Chemical Society in 2015. In this latest study, the team demonstrated the practical application of this method by producing medically relevant proteins -- including the functional region of the breast cancer drug Herceptin. The team showed that the new proteins survive longer in conditions similar to those found in the human body compared with existing proteins containing cysteine.Funding for this research was provided by the Welch Foundation, the National Science Foundation, the U.S. Army Research Office and the National Cancer Institute.The University of Texas at Austin is committed to transparency and disclosure of all potential conflicts of interest. University investigators involved in this research have submitted required financial disclosure forms with the university. UT Austin filed patent applications on the technology described in this news release, and the patents were licensed earlier this year to form a startup to develop improved protein therapeutics. Ellington and Thyer have equity ownership in the biotech startup.
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Genetically Modified
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