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May 30, 2018
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https://www.sciencedaily.com/releases/2018/05/180530151831.htm
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Cellular recycling process is key to longer, healthier life
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Building on two decades of research, investigators at UT Southwestern have determined that "cellular housekeeping" can extend the lifespan and healthspan of mammals.
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A study jointly led by Drs. Salwa Sebti and Álvaro Fernández, postdoctoral researchers in the Center for Autophagy Research, found that mice with persistently increased levels of autophagy -- the process a cell uses to dispose of unwanted or toxic substances that can harm cellular health -- live longer and are healthier. The study, published online today, is found in "Specifically, they have about a 10 percent extension in lifespan and are less likely to develop age-related spontaneous cancers and age-related pathological changes in the heart and the kidney," said Dr. Beth Levine, Director of the Center for Autophagy Research at UT Southwestern.Twenty years ago, Dr. Levine and her colleagues discovered beclin 1 -- a key gene in the biological process of autophagy. The group's research has since shown that autophagy is important in many aspects of human health, such as preventing neurodegenerative diseases, combating cancer, and fighting infection.In 2003, Dr. Levine's team found that the genetic machinery required for autophagy was essential for the lifespan extension observed in long-lived mutant roundworms."Since then, it has become overwhelmingly clear that autophagy is an important mechanism necessary for the extended lifespan that is observed when model organisms are treated with certain drugs or when they have mutations in certain signaling pathways," said Dr. Levine, also a Professor of Internal Medicine and Microbiology who holds the Charles Cameron Sprague Distinguished Chair in Biomedical Science. "The body's natural ability to perform autophagy declines with aging, which likely contributes to the aging process itself."Yet a crucial question remained unanswered: Is increased autophagy throughout mammalian life safe and beneficial? In other words, can autophagy extend lifespan and improve healthspan?To answer this question, Dr. Levine and her UTSW colleagues created a genetically engineered mouse that had persistently increased levels of autophagy. The researchers made a mutation in the autophagy protein Beclin 1 that decreases its binding to another protein, Bcl-2, which normally inhibits Beclin 1's function in autophagy. As the researchers expected, these mice had higher levels of autophagy from birth in all of their organs.Last summer, Dr. Congcong He, a former trainee in Dr. Levine's laboratory at UT Southwestern who originally made the mice, reported in Additionally, in collaboration with Dr. Ming Chang Hu, Associate Professor of Internal Medicine and Pediatrics who holds the Makoto Kuro-o Professorship in Bone and Kidney Research, and Dr. Orson Moe, Professor of Internal Medicine and Physiology who holds The Charles Pak Distinguished Chair in Mineral Metabolism and the Donald W. Seldin Professorship in Clinical Investigation, the "These studies have important implications for human health and for the development of drugs to improve it," said Dr. Levine, who is also a Howard Hughes Medical Institute Investigator. "They show that strategies to increase the cellular housekeeping pathway of autophagy may retard aging and aging-related diseases. The results suggest that it should be safe to increase autophagy on a chronic basis to treat diseases such as neurodegeneration. Furthermore, they reveal a specific target for developing drugs that increase autophagy -- namely the disruption of Beclin 1 binding to Bcl-2."Dr. Levine's group is collaborating with Dr. Jef De Brabander, Professor of Biochemistry and a member of the Harold C. Simmons Comprehensive Cancer Center who holds the Julie and Louis Beecherl, Jr. Chair in Medical Science, and his team to synthesize such drugs. Based on the results reported in the Nature study, drugs acting through this mechanism might be expected to improve the health and prolong the lifespan of human beings.
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May 23, 2018
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https://www.sciencedaily.com/releases/2018/05/180523133324.htm
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Genetic diversity helps protect against disease
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So much for survival of the fittest -- diversity is the key: a team of researchers from the Leibniz-Institute of Freshwater Ecology and Inland Fisheries (IGB) has succeeded in demonstrating experimentally that genetic diversity makes populations more resistant to disease.
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Why is it that animal and plant species throughout the world have different genetic variants within their particular species, even though it is supposed to be the "fittest" gene pool that survives? According to a common theory in evolutionary biology, it is to enable the species to respond more effectively to changes in the environment, such as the occurrence of disease. However, experimental evidence to support this theory is very difficult to obtain: After all, it is virtually impossible to observe how evolutionary trends develop in most animal and plant species -- their generation times are simply too long.A team led by IGB researcher and evolutionary ecologist Dr. Ramsy Agha has now investigated the evolution of the fungal parasite The scientists permitted the adaptation of If, on the other hand, the cyanobacteria were genetically diverse, these effects did not occur. The parasite failed to adapt, and the state of the disease remained unchanged. Genetic diversity in cyanobacteria evidently slows down the adaptation of the parasite, increasing their resistance to disease."Our findings are also significant for ecosystem research in general, because they help us to explain why a high degree of diversity in populations may be valuable for their preservation," said Agha. He and his team want to investigate next what happens when not only the parasite, but also the host population is permitted to adapt to changed conditions. The researchers hope to gain further insights into how disease -- generally perceived as a negative phenomenon -- is a crucial natural process that promotes and preserves biological diversity.
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Genetically Modified
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May 22, 2018
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https://www.sciencedaily.com/releases/2018/05/180522123316.htm
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Researchers build artificial cellular compartments as molecular workshops
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How to install new capabilities in cells without interfering with their metabolic processes? A team from the Technical University of Munich (TUM) and the Helmholtz Zentrum München have altered mammalian cells in such a way that they formed artificial compartments in which sequestered reactions could take place, allowing the detection of cells deep in the tissue and also their manipulation with magnetic fields.
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Prof. Gil Westmeyer, Professor of Molecular Imaging at TUM and head of a research team at the Helmholtz Zentrum München, and his team accomplished this by introducing into human cells the genetic information for producing bacterial proteins, so-called encapsulins, which self-assemble into nanospheres. This method enabled the researchers to create small, self-contained spaces -- artificial cellular compartments -- inside mammalian cells.The great strength of the little spheres is that they are non-toxic to the cell and enzymatic reactions can take place inside them without disturbing the cell's metabolic processes. "One of the system's crucial advantages is that we can genetically control which proteins, for example, fluorescent proteins or enzymes, are encapsulated in the interior of the nanospheres," explains Felix Sigmund, the study's first author. "We can thus spatially separate processes and give the cells new properties."But the nanospheres also have a natural property that is especially important to Westmeyer's team: They can take in iron atoms and process them in such a way that they remain inside the nanospheres without disrupting the cell's processes. This sequestered iron biomineralization makes the particles and also the cells magnetic. "To render cells visible and controllable remotely by making them magnetic is one of our long-term research goals. The iron-incorporating nanocompartments are helping us to take a big step towards this goal," explains Westmeyer.In particular, this will make it easier to observe cells using different imaging methods: Magnetic cells can also be observed in deep layers with methods that do not damage the tissue, such as Magnetic Resonance Imaging (MRI). In collaboration with Dr. Philipp Erdmann and Prof. Jürgen Plitzko from the Max Planck Institute of Biochemistry, the team could additionally show that the nanospheres are also visible in high-resolution cryo-electron microscopy. This feature makes them useful as gene reporters that can directly mark the cell identity or cell status in electron microscopy, similar to the commonly used fluorescent proteins in light microscopy. Moreover, there are even additional advantages: Cells that are magnetic can be systematically guided with the help of magnetic fields, allowing them to be sorted and separated from other cells.One possible future use of the artificial cellular compartments is, for example, cell immunotherapies, where immune cells are genetically modified in such a way that they can selectively destroy a patient's cancer cells. With the new nanocompartments inside the manipulated cells, the cells could in the future be possibly located easier via non-invasive imaging methods. "Using the modularly equipped nanocompartments, we might also be able to give the genetically modified cells new metabolic pathways to make them more efficient and robust," explains Westmeyer. "There are of course many obstacles that have to be overcome in preclinical models first, but the ability to genetically control modular reaction vessels in mammalian cells could be very helpful for these approaches."
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May 17, 2018
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https://www.sciencedaily.com/releases/2018/05/180517142605.htm
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Pesticides: What happens if we run out of options?
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To slow the evolutionary progression of weeds and insect pests gaining resistance to herbicides and pesticides, policymakers should provide resources for large-scale, landscape-level studies of a number of promising but untested approaches for slowing pest evolution. Such landscape studies are now more feasible because of new genomic and technological innovations that could be used to compare the efficacy of strategies for preventing weed and insect resistance.
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That's the takeaway recommendation from a North Carolina State University review paper addressing pesticide resistance published today in the journal Pesticide resistance exacts a tremendous toll on the U.S. agricultural sector, costing some $10 billion yearly. Costs could also increasingly accrue on human lives. If insecticide-coated bed nets and complementary insecticide spraying failed to slow the transmission of malaria by pesticide-resistant mosquitoes, for example, the human health costs in places like Africa could be catastrophic."What is the impact on people if these herbicides and pesticides run out?" said Fred Gould, William Neal Reynolds Professor of Agriculture at NC State and the corresponding author of the paper. "Resistance to pesticides is rising in critical weed and insect species, threatening our ability to harness these pests. Weed species have evolved resistance to every class of herbicide in use, and more than 550 arthropods have resistance to at least one pesticide."Consider glyphosate, the powerhouse weed killer used ubiquitously in the United States to protect major crops like corn and soybeans. A bit more than 20 years ago, crops were genetically engineered to withstand glyphosate, allowing them to survive exposure to the chemical while weeds perished. By 2014, some 90 percent of planted U.S. corn, soybean and cotton crops were genetically modified to withstand glyphosate. Unfortunately, as the evolutionary arms race progresses, many weeds have figured out how to evolve resistance to glyphosate, making the chemical increasingly ineffective and forcing farmers to look for other or new solutions.Some of these "new" solutions are actually old, as the herbicides 2,4-D and Dicamba, developed in the 1940s and 1960s, respectively, are currently getting a second look as possible widespread weed weapons."We're working down the list of available tools to fight weeds and insect pests," said Zachary Brown, assistant professor of agricultural and resource economics at NC State and a co-author of the paper. "It hasn't been economically feasible to develop new herbicides to replace glyphosate, for example, so what's old is becoming new again. But the current incentives don't seem to be right for getting us off this treadmill."Besides ecology and economics, the authors stress that sociological and political perspectives also set up roadblocks to solving the problems of pest resistance. Cultural practices by farmers -- whether they till their land or not, how they use so-called refuges in combination with genetically modified crop areas and even how often they rotate their crops -- all play a big role in pest resistance."Any proposed solutions also need to include perspectives from the individual farmer, community and national levels," said Jennifer Kuzma, Goodnight-NC GSK Foundation Distinguished Professor and co-author of the paper.The authors propose large-scale studies that would test the efficacy of a particular pesticide resistance strategy in one large area -- thousands of acres or more -- and how weeds and crop yields compare to large "control" areas that don't utilize that particular strategy. Farmers would receive incentives to participate; perhaps subsidies already allocated to farmers could be shifted to provide these participatory incentives, the authors suggest."In the end, are we going to outrun the pests or are they going to outrun us?" Gould said.
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Genetically Modified
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May 8, 2018
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https://www.sciencedaily.com/releases/2018/05/180508111745.htm
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Tissue-engineered human pancreatic cells successfully treat diabetic mice
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Researchers tissue-engineered human pancreatic islets in a laboratory that develop a circulatory system, secrete hormones like insulin and successfully treat sudden-onset type 1 diabetes in transplanted mice.
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In a study published by "This method may serve as a principal curative strategy for treating type 1 diabetes, of which there are 79,000 new diagnoses per year," said Takanori Takebe, MD, a physician-scientist at the Cincinnati Children's Center for Stem Cell and Organoid Medicine. "This is a life-threatening disease that never goes away, so developing effective and possibly permanent therapeutic approaches would help millions of children and adults around the world."Takebe, who has a dual appointment in the Department of Regenerative Medicine at YCU, stressed the technology needs additional research before it can be used therapeutically in a clinic. He is the study's co-lead investigator along with YCU colleague, Hideki Taniguchi, MD, PhD.Scientists tested their processing system with donated human organ cells (pancreas, heart, brain, etc.), with mouse organ cells and with induced pluripotent stem cells (iPS). Reprogrammed from a person's adult cells (like skin cells), iPS cells act like embryonic cells and can form any tissue type in the body.The tissue-engineering process also uses two types of embryonic-stage progenitor cells, which support formation of the body and its specific organs. The progenitor cells are mesenchymal stem cells (MSNs) and human umbilical vascular endothelial cells (HUVECs).Using either donated organ cells, mouse cells or iPS cells, the researchers combined these with MSNs, HUVECs along with other genetic and biochemical material that cue the formation of pancreatic islets. In conditions that nourish and nurture the cells, the ingredients condensed and self-organized into pancreatic islets.After the tissue-engineered islets were transplanted into humanized mouse models of severe type 1 diabetes, they resolved the animals' disease, report researchers.Human pancreatic islets already can be transplanted into diabetic patients for treatment. Unfortunately, the engraftment success rate is relatively low because the tissues lose their vascularization and blood supply as islets are being processed before transplant. This makes it difficult to get the maximum health benefit for patients getting these procedures, the authors write.And although stem cell-based tissue engineering has tremendous therapeutic potential, its future clinical use still faces the critical challenge of ensuring a blood supply to nourish the transplanted tissues, according to researchers."We need a strategy that ensures successful engraftment through the timely development of vascular networks," said Taniguchi. "We demonstrate in this study that the self-condensation cell culturing system promotes tissue vascularization."Pancreatic islets tissue-engineered in the current generated by the process not only quickly developed a vascular network after transplant into animal models of type 1 diabetes, the tissues also functioned efficiently as part of the endocrine system -- secreting hormones like insulin and stabilizing glycemic control in the animals.Takebe's and Taniguchi's research team already demonstrated the ability to use a "self-condensation" cell culture process using iPS cells to tissue engineer three-dimensional human liver organoids that can vascularize after transplant into laboratory mice. But the ability to generate organ tissue fragments that vascularize in the body -- like pancreatic islets -- had been an elusive goal until the current study, investigators said.
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Genetically Modified
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May 7, 2018
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https://www.sciencedaily.com/releases/2018/05/180507111840.htm
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Universal antibody drug for HIV-1 prevention and immunotherapy
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A research team led by scientists at AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine of The University of Hong Kong (HKU) invents a universal antibody drug against HIV/AIDS. By engineering a tandem bi-specific broadly neutralizing antibody, the team found that this novel antibody drug is universally effective not only against all genetically divergent global HIV-1 strains tested but also promoting the elimination of latently infected cells in a humanized mouse model. The new findings are now published in the April issue of
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AIDS remains an incurable disease. In the world, HIV/AIDS has resulted in estimated 40 million deaths while 36.9 million people are still living with the virus. To end the HIV/AIDS pandemic, it is important to discover either an effective vaccine or a therapeutic cure. There are, however, two major scientific challenges: the tremendous HIV-1 diversity and the antiviral drug-unreachable latency. Since it is extremely difficult to develop an appropriate immunogen to elicit broadly neutralizing antibodies (bnAbs) against genetically divergent HIV-1 subtypes, developing existing bnAbs as passive immunization becomes a useful approach for HIV-1 prophylaxis and immunotherapy.Previous studies have investigated the potency, breadth and crystal structure of many bnAbs including their combination both in vitro and in vivo. Naturally occurring HIV-1 resistant strains, however, are readily found against these so-called bnAbs and result in the failure of durable viral suppression in bnAb-based monotherapy. To improve HIV-1 neutralization breadth and potency, bispecific bnAb, which blocks two essential steps of HIV-1 entry into target cells, have been engineered and show promising efficacy in animal models. Before the publication, tandem bi-specific bnAb has not been previously investigated in vivo against HIV-1 infection.The HKU research team invented a single gene-encoded tandem broadly neutralizing antibody, titled "BiIA-SG," which "kills two birds with one stone." By attaching to host protein CD4, BiIA-SG strategically ambushes invading HIV-1 particles to protect CD4 positive T cells. BiIA-SG not only displays a potent activity against all three panels of 124 genetically divergent global HIV-1 strains tested, but also prevents diverse live viral challenges completely in humanized mice. Moreover, gene transfer of BiIA-SG achieves pro-longed drug availability in vivo, leading to a promising efficacy of eliminating HIV-1 infected cells in humanized mice. Therefore, the research team provides a proof-of-concept that BiIA-SG is a novel universal antibody drug for prevention and immunotherapy against HIV-1 infection.The accumulated number of HIV-1 infections has more than doubled from 4,443 diagnostic cases in 2009 to 9,091 in 2017, despite the timely introduced combination antiretroviral therapy and prevention interventions in Hong Kong. Currently, the estimated annual cost is over HK$550 millions for antiretroviral drugs alone per year in Hong Kong, not to mention the rising issues of life-long financial burdens, drug toxicity and resistant viruses. The newly invented universal antibody drug brings the hope to fight these issues. With significantly improved breadth and potency, BiIA-SG will hopefully be the first "Made in Hong Kong" anti-HIV-1 antibody drug for clinical development.
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Genetically Modified
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May 1, 2018
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https://www.sciencedaily.com/releases/2018/05/180501161757.htm
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Formate prevents most folic acid-resistant neural tube defects in mice
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Maternal folic acid supplementation has reduced the prevalence of neural tube defects, one of the most common structural malformations in people, by up to 80 percent. However, many infants are still born with a neural tube defect that appears to be resistant to folic acid supplementation. In this study, a multi-institutional research team has developed a novel folic acid-resistant neural tube defect mouse model of the human condition by silencing the Slc25a32 gene, and, in most of the mutant mice, neural tube defects can be prevented by formate supplementation. A parallel genetic study of individuals with neural tube defects found a patient carrying a non-functional mutation of the SLC25A32 gene. Together, these findings support the search for supplements that might prevent folic acid-resistant human neural tube defects in the future. The study appears in the
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"Folic acid supplementation is considered one of the most significant public health breakthroughs in recent years. By providing mandatory folic acid fortification, as 87 countries, including the U.S. since 1998, now do, we can prevent the vast majority of neural tube defect cases. But in about 30 percent of the cases, folic acid is not protecting," said corresponding author Dr. Richard Finnell, professor in the Center for Precision Environmental Health at Baylor College of Medicine.The success obtained with folic acid supplementation suggested that there might be other nutrients that could prevent neural tube defect cases that do not respond to folic acid. To find these nutrients, Finnell and his colleagues studied the metabolic pathway involving folic acid. The body requires folic acid to accomplish a number of cellular processes, including the synthesis of the building blocks of DNA, which is essential for proliferating cells."Lacking enough folic acid inhibits DNA synthesis and cell proliferation and can have serious consequences, especially in the growing embryo which is engaged in active cell proliferation to develop a complete baby," Finnell said. "Folic acid deficiency in the embryo, together with genetic and environmental factors, can result in failed closure of the neural tube and lead to defects."As the researchers studied the metabolic pathway involving folic acid, called one carbon metabolism, they focused on formate, a compound derived from folic acid in a cellular organelle called the mitochondria that also contributes to DNA synthesis. Previous laboratory studies by collaborators at the University of Texas at Austin had identified the Mthfd1l gene, which encodes for an enzyme that is involved in the synthesis mitochondrial formate. Mice lacking this gene had neural tube defects that were partially rescued when the mother was given formate supplementation."In our study, we asked whether disrupting formate synthesis by silencing the Slc25a32 gene that transports the precursors of formate into the mitochondria would also result in neural tube defects in mice," said first author Dr. Yunping Lei, assistant professor in the Center for Precision Environmental Health at Baylor College of Medicine. "When we genetically engineered mice to lack the formate transport protein produced by the Slc25a32 gene, all of the mutant mice had neural tube defects. When we provided pregnant mice with extra formate, we were able to prevent neural tube defects in 78 percent of the offspring carrying a defective Slc25a32 gene."To determine whether the findings in mice could be connected to human neural tube defects, the researchers conducted genomic studies in a cohort of patients with this condition and found one individual carrying a non-functional variant of the SLC25A32 gene."We know that the patient has a neural tube defect, but we would need further studies to determine how involved the SLC25A32 gene is in the condition," Finnell said. "Neural tube defects can be caused by variants in over 300 genes in the mouse, so we anticipate that many genes also are likely to be involved in the human condition.""I am most excited about the connection we have made between the mouse model and the human condition through the SLC25A32 gene," Lei said. "We now have a novel mouse model of human neural tube defects in which we can study the complex interactions between genetics and the environment that lead to this condition, and explore strategies to prevent the defects from happening.""My lab is all about preventing preventable birth defects," Finnell said. "Even though we do fortify foods with folic acid, there are still babies born with neural tube defects. Folic acid has been a major public health advance, but the problem has not disappeared. We cannot lose sight of the fact that babies can still be born with neural tube defects even when the mothers take folic acid supplements."
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Genetically Modified
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April 26, 2018
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https://www.sciencedaily.com/releases/2018/04/180426125953.htm
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Spawing better ways to combat crop-killing fungus
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About 21 million years ago, a fungus that causes a devastating disease in rice first became harmful to the food that nourishes roughly half the world's population, according to an international study led by Rutgers University-New Brunswick scientists.
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The findings may help lead to different ways to fight or prevent crop and plant diseases, such as new fungicides and more effective quarantines.Rice blast, the staple's most damaging fungal disease, destroys enough rice to feed 60 million people annually. Related fungal pathogens (disease-causing microorganisms) also infect turfgrasses, causing summer patch and gray leaf spot that damage lawns and golf courses in New Jersey and elsewhere every summer. And now a new fungal disease found in wheat in Brazil has spread to other South American countries.Results from the study published online in "The rice blast fungus has gotten a lot of attention in the past several decades but related species of fungi draw little attention, largely because they're not as severe or not harmful," Zhang said. "But they're all genetically related and the relatives of severe pathogens have been little-studied. You have to know your relatives to have a holistic understanding of how the rice blast pathogen became strong and others did not."The study is the outcome of a 2016 international symposium at Rutgers-New Brunswick hosted by Zhang and Debashish Bhattacharya, study senior author and distinguished professor in the Department of Biochemistry and Microbiology. The National Science Foundation, Rutgers Center for Turfgrass Science, and School of Environmental and Biological Sciences funded the symposium by researchers from the U.S., France and South Korea.The scientists studied Magnaporthales, an order of about 200 species of fungi, and some of the new members were discovered in the New Jersey Pine Barrens. About half of them are important plant pathogens like the rice blast fungus -- ranked the top fungal pathogen out of hundreds of thousands. After the first sign of infection, a rice field may be destroyed within days, Zhang said.To get a holistic understanding of how the rice blast fungus evolved, scientists genetically sequenced 21 related species that are less harmful or nonpathogenic. They found that proteins (called secretomes) that fungi secrete are especially abundant in important pathogens like the rice blast fungus.Based on previous research, the proteins perhaps became more abundant over time, allowing the fungi to infect crops, Zhang said. The researchers identified a list of genes that are abundant in pathogens but less so in nonpathogens, so the abundant genes might promote pathogens that can infect crops. The results will allow scientists to look into the mechanism behind the infection process."With climate change, I think the rice blast problem can only get worse because this is a summer disease in warm climates where rice is grown," Zhang said, adding that wheat, turfgrass and other important plants may also be affected.
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Genetically Modified
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April 26, 2018
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https://www.sciencedaily.com/releases/2018/04/180426125937.htm
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CRISPR/Cas9 silences gene associated with high cholesterol
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Biomedical engineers at Duke University have used a CRISPR/Cas9 genetic engineering technique to turn off a gene that regulates cholesterol levels in adult mice, leading to reduced blood cholesterol levels and gene repression lasting for six months after a single treatment.
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This marks the first time researchers have delivered CRISPR/Cas9 repressors for targeted therapeutic gene silencing in adult animal models. The study appeared online in The CRISPR/Cas9 system is based on an antiviral defense mechanism in bacteria in which the Cas9 enzyme recognizes the viral DNA sequences of previous infections and cuts up invading DNA during re-infection. Researchers have engineered the CRISPR/Cas9 system to not only locate and cut specific sequences of DNA, but to also turn on or off the expression of targeted genes without making permanent changes to the DNA coding sequence.While this CRISPR/Cas9 repressor technique has emerged as a robust tool for disrupting gene regulation in cell culture models, it had not yet been adapted for delivery to adult animals for applications such as gene therapy.In their most recent study, Charles Gersbach, the Rooney Family Associate Professor of Biomedical Engineering at Duke, and members of his laboratory developed an approach to efficiently package and deliver the CRISPR/Cas9 repressor system to mice. They tested their delivery system by silencing Pcsk9, a gene that regulates cholesterol levels. While several drugs have been developed to treat high cholesterol and cardiovascular disease by blocking the activity of Pcsk9, this new approach would prevent Pcsk9 from being made."We previously used these same types of tools to turn genes on and off in cultured cells, and we wanted to see if we could also deliver them to animal models with an approach that is relevant for gene therapy," Gersbach said. "We wanted to change the genes in a way that would have a therapeutic outcome, and Pcsk9 is a useful proof-of-concept given its role regulating cholesterol levels, which in turn affect health issues like heart disease."To test the targeted Pcsk9 repressor in an adult animal, the team opted to use adeno-associated viral (AAV) vectors -- small viruses that have been engineered to target a variety of tissue types in human gene therapy clinical trials. Due to the vector's small cargo limit, the team couldn't use the common Cas9 enzyme from Streptococcus pyogenes. Instead, they opted to use a smaller Cas9 from Staphylococcus aureus. They also deactivated the DNA-cutting function of Cas9, creating a "dead" version of the enzyme, dCas9, that binds to but does not cut the targeted DNA sequence.The dCas9 can be combined with a KRAB protein that silences gene expression, creating a CRISPR/Cas9 repressor that blocks transcription, reduces chromatin accessibility, and silences gene expression without altering the underlying DNA sequence. Using an adenovirus vector to deliver CRISPR/Cas9-based repressors to the mouse liver, the researchers reduced Pcsk9 and cholesterol levels in treated mice.While the experiment was successful, the researchers also observed release of liver enzymes into the blood only in treatments that included Cas9. While these liver enzyme levels remained below a critical threshold and normalized over time, their elevated levels indicated that the therapy potentially caused immune responses in the liver, where the virus and Cas9 enzyme accumulate. That raises questions about the efficacy of multiple injections."One of the interesting things we found looked like an immune response against the Cas9 protein," said Pratiksha Thakore, the PhD student who led the work in Gersbach's lab. "Following injection, we saw that levels of our target gene, Pcsk9, were reduced, but we also observed increases in expression of many immune cell genes, which indicates that immune cells were infiltrating the liver after we delivered Cas9 to the mice. Gaining a better understanding of this immune response and how to modulate it will be important for using Cas9 technologies for therapies."As researchers develop new ways to use the CRISPR/Cas9 for therapy and research, more information is emerging on how the immune system of living organisms responds to delivery of CRISPR/Cas9 system. Because the Cas9 enzyme is derived from bacteria, the immune system may recognize it as a foreign protein from an invading organism and mount a response. There is also concern that potential patients for a CRISPR/Cas9-based therapy may already be primed to harbor immune responses against these systems, because the Cas9 enzymes most commonly used in research come from common bacteria to which humans are routinely exposed."The field is just starting to look at this, and it's clear that immune response is an important issue," said Gersbach. "Although we did see an immune response in the mice when we administered Cas9, the levels of liver enzymes in the serum seemed to mitigate over time without any intervention, and the effect of Pcsk9 repression was sustained regardless."As they continue the research, Gersbach and his collaborators hope to gather more information to better understand the immune response against Cas9 and stability of epigenetic modulation."There are still lots of things for us to explore with this approach," said Thakore. "CRISPR/Cas9 tools have worked so well in cell culture models that it's exciting to apply them more in vivo, especially when we're examining important therapeutic targets and using delivery vehicles that would be relevant to treating human diseases."
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Genetically Modified
| 2,018 |
April 16, 2018
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https://www.sciencedaily.com/releases/2018/04/180416121539.htm
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Two is better than one to improve brain function in Alzheimer's disease mouse model
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Using two complementary approaches to reduce the deposits of amyloid-beta in the brain rather than either approach alone improved spatial navigation and memory in a mouse model of Alzheimer's disease. These findings suggest that similar combination treatments also might help patients with Alzheimer's disease in the future. The study appears in the
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"Many of the therapies that are currently being developed to treat Alzheimer's disease focus on reducing the levels of amyloid-beta," said corresponding author Dr. Joanna Jankowsky, associate professor of neuroscience, molecular and cellular biology, neurology, and neurosurgery at Baylor College of Medicine. "Amyloid-beta is a small protein that is abundant in the amyloid plaques that characterize Alzheimer's disease."All previous clinical trials designed to reduce the levels of amyloid-beta using one therapy at a time have had limited success. Jankowsky and her colleagues have previously shown that combining two complementary treatments to reduce amyloid-beta not only curbs further plaque growth, but also helps to clear plaques that have already formed. With a combination approach, animals finished the study with less amyloid than they had at the start of treatment. In this study, Jankowsky and colleagues determined for the first time the benefits of dual amyloid-beta treatment on brain functions, such as spatial navigation and memory, in a mouse model of Alzheimer's disease.To reduce the levels of amyloid-beta the researchers attacked the problem from two fronts. On one front, they worked with a mouse model genetically engineered to stop the production of amyloid-beta. On the other front, they promoted the elimination of amyloid-beta with antibodies that bind to this protein and promote its elimination."Using this combined approach, we were able to reduce the levels of amyloid-beta, but, importantly, restored spatial learning and memory to the level observed in healthy mice," Jankowsky said.The other contribution of this study was the identification of potential alternative therapeutic targets."Dr. Angie Chiang, a recent Ph.D. graduate from my lab and the first author of this work, was interested in identifying a molecular mechanism supporting our observations and decided to look at the mTOR pathway," Jankowsky said.The mTOR protein is part of a complex that carries out a multitude of functions within cells, including the formation of synapses -- the connections between neurons -- their maintenance and plasticity. This pathway also regulates autophagy, one of the cellular processes that eliminates amyloid-beta. The mTOR pathway sits at the intersection of these processes that Jankowsky and her colleagues found changed as a result of treatment."The neurons had roadblocks that were causing them to swell and malfunction; the double treatment helped clear that roadblock," Jankowsky said. "Also, synapses lost as a result of the amyloid deposits were rebuilt, and the animals improved learning and memory."The researchers showed that the mTOR pathway correlates with brain improvements observed in their mice and suggest that future studies might test whether the pathway is necessary to mediate such improvements."If mTOR signaling is necessary for the improvements, it might become an alternative target for combination therapy," Jankowsky said. "We hope that our findings will be valuable in discussions about future human clinical trials."
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Genetically Modified
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April 11, 2018
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https://www.sciencedaily.com/releases/2018/04/180411131649.htm
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Mutant ferrets offer clues to human brain size
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A genetically engineered ferret could help reveal how humans got their big brains.
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By inactivating a gene linked to abnormally small brain size in humans, researchers have created the first ferret with a neurological mutation. Although the original impetus of the work was to study human brain disease and development, says Howard Hughes Medical Institute (HHMI) Investigator Christopher Walsh, the results also shed light on how the human brain expanded during the course of evolution."I'm trained as a neurologist, and study kids with developmental brain diseases," says Walsh, of Boston Children's Hospital. "I never thought I'd be peering into the evolutionary history of humankind."He and colleagues, along with Byoung-Il Bae's lab at Yale University, report the work April 11, 2018, in the journal Usually, the outer layer of the human brain, called the cerebral cortex, is large and highly folded. But things can go wrong when the embryonic brain is being built, resulting in a much smaller cortex. This occurs in microcephaly, a condition where babies have significantly smaller heads and brains than normal. Microcephaly can have a genetic root, and has also been linked to recent outbreaks of the Zika virus.Researchers have identified genes that play a role in the condition, some of which are essential for cerebral cortex growth during embryonic development. Mutations in a gene called Scientists have studied microcephaly in mice to better understand the condition in humans, but learning about human disorders from mice can be tricky. A mouse brain is a thousand times smaller than a human brain, and lacks several kinds of brain cells that are abundant in humans. Inactivating This prompted Bae and Walsh's team to genetically inactivate, or "knock out," Still, scientists haven't done much research on ferret genetics. The whole idea of an Walsh, Bae, and their colleagues discovered that their ferrets model human microcephaly much more accurately than do mice. The ferrets displayed severely shrunken brains, with up to 40 percent reduced brain weight. And, as in humans with the condition, cortical thickness and cell organization were preserved.What's more, the ferrets reveal a possible mechanism for how human brains have grown over evolutionary time. Over the last seven million years, human brain size has tripled. Most of this expansion has occurred within the cerebral cortex.Indeed, in the mutant ferrets, researchers traced the cerebral cortex deficits to a type of stem cell called outer radial glial cells (ORGs). ORGs are created by stem cells capable of making all sorts of different cells in the cortex. Walsh's team found that That's a clue that the gene could have played a role in the evolution of the human brain. "Nature had to solve the problem of changing the size of the human brain without having to reengineer the whole thing," Bae says.In humans, a few genes associated with centriole proteins, including Overall, he says, the study demonstrates the advantages of using ferrets to study some human neurological disorders. It also points to new mechanisms at work in the brain development of individuals and in species like humans over evolutionary time."It makes sense in retrospect," Walsh says. "The genes that put our brains together during development must have been the genes that evolution tweaked to make our brains bigger."
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April 5, 2018
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https://www.sciencedaily.com/releases/2018/04/180405150057.htm
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Injecting gene cocktail into mouse pancreas leads to human-like tumors
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Novel technology developed at UT Health San Antonio gives rise to mouse pancreatic tumors that have the same traits as human pancreatic cancer. A U.S. patent is pending on the invention.
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The technology could revolutionize studies of pancreatic cancer initiation and progression and spur new drug development. An article published in the journal Scientists study pancreatic cancer by genetically engineering mice to develop the disease or by transplanting tumors into rodents to test drug activity. In both cases, the resulting tumors provide an artificial, rather than true, picture of the human disease, said the technology's inventor, Bruno Doiron, Ph.D., of UT Health San Antonio."For a decade, we have failed in treating pancreatic cancer because we didn't have a good way to test new drugs," Dr. Doiron, an assistant professor in the Joe R. & Teresa Lozano Long School of Medicine, said.Pancreatic cancer kills 95 percent of patients within five years of diagnosis. Advances in therapy have been negligible, with chemotherapies only able to extend survival by a few months. Need for a new study tool is therefore urgent.Dr. Doiron and his lab team are injecting a modified virus into the adult mouse pancreas. The virus is a delivery vehicle for two pro-cancer molecules (called KrasG12D mutation and shRNA p53) that are present in human pancreatic tumors. Upon injection, the virus permeates the pancreas with these pro-cancer factors. The effect is contained; only the pancreas is altered by this molecular cocktail. When the mice reach 28 to 30 weeks of age, tumors develop that resemble human pancreatic cancer."I take the two major genetic mutations involved in human pancreatic cancer and inject them directly to the pancreas, and tumors develop in the adult mice," Dr. Doiron said. "This bypasses the artificial manipulation introduced by other methods, and spontaneous cancers develop that mimic those found in people."The procedure is performed in mice that are not of any special breeding or stock. They are from many different parents. This ensures that the development of pancreatic cancer is in a random nature, the way it occurs in humans.The Obesity and diabetes are major risk factors for pancreatic cancer. The risk of pancreatic cancer is increased 1.5-fold in obese subjects and two- to threefold in people with diabetes. The new technology can be used to delve into this link."The prevalence of obesity and Type 2 diabetes has reached epidemic proportions during the last two decades in the U.S. and worldwide, and this may explain, in part, why the death rate from pancreatic cancer has not declined in the same way as it has for some other cancers," Dr. Doiron said.Ruben A. Mesa, M.D., FACP, director of the Mays Cancer Center, the newly named center home to UT Health San Antonio MD Anderson Cancer Center, commented: "This important work by Dr. Doiron and colleagues will allow us to better predict which treatments for the devastating disease of pancreatic cancer will be effective. These discoveries are a much-needed advance on efforts to cure pancreatic cancer."
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March 29, 2018
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https://www.sciencedaily.com/releases/2018/03/180329141052.htm
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Mice 'eavesdrop' on rats' tear signal
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Tears might not seem to have an odor. But studies have shown that proteins in tears do act as pheromonal cues. For example, the tear glands of male mice produce a protein that makes females more receptive to sex. Now researchers reporting in
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The findings provide the first example of "olfactory eavesdropping" in the predator-prey communications of mammals, the researchers say.Researchers led by Kazushige Touhara at the University of Tokyo, Japan, had earlier described a pheromone protein in mouse tears that they call ESP1. In the new study, they hypothesized that proteins secreted in the tear fluid of a predator (rats) might trigger behavioral changes in their prey (mice).First, they identified a novel compound in rats' tear fluid, which they call cystatin-related protein 1 (CRP1). The protein, produced by male rats, activates receptors in the vomeronasal organ of female rats, prompting them to stop. As the researchers suspected, the protein also activates receptors in the vomeronasal organs of mice.When mice detect rat CRP1, they report, it activates a defensive circuit in the rodents' brains. As a result, the mice stop moving around as their body temperature and heart rate drop.Touhara's team found that multiple receptors in the mouse vomeronasal organ detect the rat protein. When the researchers genetically modified mice to block expression of one of those receptors, the animals stopped responding to rat CRP1."Our study shows that rat CRP1 is a putative sex pheromone in rats and that mice eavesdrop the rat pheromone as a predator signal," Touhara says.Touhara says that rat CRP1 is a member of the cystatin superfamily, a group best known for its role in inhibiting enzymes that degrade proteins. That a member of this superfamily would serve as a chemical signal comes as a surprise.The researchers say that future studies will explore how rat-derived vomeronasal signals are encoded to produce distinct behaviors in the mice. The discovery also opens a new avenue to explore the evolution of predator-prey communications.This work was supported by the JST ERATO Touhara Chemosensory Signal and the JSPS.
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Genetically Modified
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March 29, 2018
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https://www.sciencedaily.com/releases/2018/03/180329141047.htm
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Pig model of Huntington's offers advantages for testing treatments
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Using genetic engineering technology, a team of scientists has established a pig model of Huntington's disease (HD), an inherited neurodegenerative disease. The researchers anticipate that the pigs could be a practical way to test treatments for HD, which is caused by a gene encoding a toxic protein that causes brain cells to die.
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The research is scheduled for publication in Although genetically modified mice have been used widely to model neurodegenerative diseases, they lack the typical neurodegeneration or overt neuronal loss seen in human brains, says corresponding author Xiao-Jiang Li, MD, PhD, distinguished professor of human genetics at Emory University School of Medicine.The pig HD model is an example that suggests large animal models could better model other neurodegenerative diseases, such as Alzheimer's, Parkinson's and ALS (amyotrophic lateral sclerosis), he says. A HD pig could be an opportunity to test if CRISPR-Cas9 gene editing can work in larger animals before clinical applications in humans.In comparison with mice, delivery of treatments to affected nervous system tissues can be better tested in pigs, because their size is closer to that of humans. The pig model of HD also more closely matches the symptoms of the human disease. Compared with non-human primate models, the pigs offer advantages of faster breeding and larger litter sizes, the researchers say.The pig model of HD was established by researchers at Emory University School of Medicine, together with colleagues at Jinan University and Chinese Academy of Sciences in Guangzhou."We think the pig model will fill an important gap," says co-senior author Shihua Li, M.D, professor of human genetics at Emory University School of Medicine. "In pigs, the pattern of neurodegeneration is almost the same as in humans, and there have been several treatments tested in mouse models that didn't translate to human."Shihua and Xiao-Jiang Li jointly run a lab at Emory, which collaborated with Liangxue Lai, PhD, associate director of the South China Institute of Stem Cells and Regeneration Medicine, Chinese Academy of Sciences. The lead author of the paper is Sen Yan at Jinan University's Guangdong-Hongkong-Macau Institute of CNS Regeneration. Yan was trained in the Li Lab as a visiting PhD student at Emory. The pigs are housed in Guangzhou.Symptoms displayed by the genetically altered pigs include movement problems. They show respiratory difficulties, which resemble those experienced by humans with HD and are not seen in mouse models of HD. In addition, the pigs show degeneration of the striatum, the region of the brain most affected by HD in humans, more than other regions of the brain.Huntington's disease is caused by a gene encoding a toxic protein (mutant huntingtin or mHTT). mHTT contains abnormally long repeats of a single amino acid, glutamine. Symptoms commonly appear in mid-life and include uncontrolled movements, mood swings and cognitive decline.Researchers used the CRISPR/Cas9 gene editing technique to introduce a segment of a human gene causing Huntington's, with a very long glutamine repeat region, into pig fibroblast cells. Then somatic cell nuclear transfer generated pig embryos carrying this genetic alteration. The alteration is referred to a "knock in" because the changed gene is in its natural context.Last year, the Li lab published a paper in The research was supported by the U.S. National Institute of Neurological Disorders and Stroke (NS101701, NS095279, NS095181), National Key Research and Development Program of China (Stem Cell and Translational Research), the National Natural Science Foundation of China, and Guangdong Province.
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March 26, 2018
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https://www.sciencedaily.com/releases/2018/03/180326090324.htm
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Let them eat xylose: Yeast engineered to grow efficiently on novel nutrients
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Researchers at Tufts University have created a genetically modified yeast that can more efficiently consume a novel nutrient, xylose, enabling the yeast to grow faster and to higher cell densities, raising the prospect of a significantly faster path toward the design of new synthetic organisms for industrial applications, according to a study published today in
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In synthetic biology, organisms such as bacteria or yeast may be transformed into "mini-factories" when fed nutrients to produce a wide range of products, from pharmaceuticals to industrial chemicals and biofuels. However, a central challenge has been the efficient conversion of abundant feedstocks into the final product, particularly when the feedstock is not something the bacteria or yeast normally "eat."In this study, the researchers noted that conventional approaches to modifying organisms to consume novel nutrients constitutively (i.e. with no "off switch") can lead to inefficiencies when the nutrient metabolic pathways are not linked to downstream pathways for stress-responses, cell growth and other functions important for the health of the organism.Taking a different approach, the researchers took a set of regulatory genes, called a GAL regulon, that normally processes galactose -- a favorite on the yeast menu of nutrients -- and replaced some of the genes with those that become activated by, and direct the breakdown of, xylose. All other genes in the GAL regulon were unchanged. In doing so, they preserved a more natural interaction between the genes that govern feeding and those that govern survival. The new synthetic regulon, dubbed XYL, enabled the yeast cells to grow more rapidly and to higher cell densities."Instead of building a metabolic framework from the ground up, we can reverse engineer existing regulons to enable an organism to thrive on a novel nutrient," said Nikhil U. Nair, Ph.D., assistant professor of chemical and biological engineering at Tufts and corresponding author of this study. "Adapting native regulons can be a significantly faster path toward the design of new synthetic organisms for industrial applications."One such application is the production of ethanol as a biofuel. Concerns have been raised that diverting significant portions of crops, such as corn, to biofuel production could have a negative impact on availability and cost of the food supply. However, xylose is a sugar derived from the otherwise indigestible parts of plant material. The ability to ferment xylose can be a path to biofuel production that does not compete with the food supply.As part of the study, Nair and his team took a closer look at what exactly accounted for the improved survival of the xylose-eating yeast organism. They found numerous genes activated in the XYL regulon-controlled yeast that upregulated pathways involved in growth, such as cell wall maintenance, cell division, mitochondrial biogenesis and adenosine triphosphate (ATP) production. Yeast strains that had constitutive (mostly unregulated) control of xylose metabolism triggered pathways related to cell stress, starvation and DNA damage."Our study applied this approach to xylose, but it suggests a broader principle -- adapting native regulons for the efficient assimilation of other non-native sugars and nutrients," said Nair. "Nature has already done the work of tuning genes and metabolic pathways to the environment of the organism. Let's make use of that when introducing something new on the menu."
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March 22, 2018
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https://www.sciencedaily.com/releases/2018/03/180322181338.htm
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Using light to turn yeast into biochemical factories
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Scientists have recently learned how to use light to control specific groups of neurons to better understand the operation of the brain, a development that has transformed areas of neuroscience.
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Researchers at Princeton University have now applied a similar method to controlling the metabolism, or basic chemical process, of a living cell. In a series of experiments, they used light to control genetically-modified yeast and increase its output of commercially valuable chemicals. The results offer scientists a powerful new tool to probe and understand the inner working of cells."This technique allows us to control the metabolism of cells in an unprecedented way," said co-lead researcher José L. Avalos, an assistant professor of chemical and biological engineering and Princeton's Andlinger Center for Energy and the Environment. "It opens the door to controlling metabolism with light."Yeast has been used for centuries to make bread, wine and beer. Through fermentation, yeast cells transform sugar into chemicals that make bread rise and turn grape juice into wine. Using their new technique, the Princeton researchers have now used fermentation and genetically-engineered yeast to produce other chemicals including lactic acid, used in food production and bioplastics, and isobutanol, a commodity chemical and an advanced biofuel.Light played a key role in the experiment because it allowed the researchers to switch on genes that they had added to the yeast cells. These particular genes are sensitive to light, which can trigger or suppress their activity. In one case, turning on and off a blue light caused the special yeast to alternate between producing ethanol, a product of normal fermentation, and isobutanol, a chemical that normally would kill yeast at sufficiently high concentration.The achievement of producing these chemicals was significant, but the researchers were intrigued by the development of light's broader role in metabolic research."It provides a new tool with the ability to do sophisticated experiments to determine how metabolism works and how to engineer it," Avalos said.In a March 21 paper in the journal Isobutanol is an alcohol used in products such as lubricants, gasoline and jet fuel replacements, and plastics. With good compatibility with gasoline infrastructure, isobutanol has properties that could make it a direct substitute for gas as a vehicle fuel. However, most attempts to create isobutanol biofuel have run into difficulties involving cost or scaling production to an industrial level. Although natural yeast fermentation produces isobutanol, it does so in miniscule amounts. Instead, yeast makes high volumes of ethanol (the alcohol in beer and wine) and carbon dioxide (a gas that makes bread rise)."Yeast don't want to make anything but ethanol; all their systems have evolved to do this," said Evan M. Zhao, a third-year Ph.D. student in Avalos' lab and lead author on the The researchers sought to overcome this barrier. They managed to suppress the yeast's evolutionary self-interest by genetically engineering it to produce large quantities of isobutanol. But they faced a major problem. Isobutanol is toxic to yeast and eventually kills yeast colonies that produce it in any significant quantity. The researchers predicted they could use a combination of genetic engineering and light to fine tune isobutanol production. Using their light-switch technique, the researchers set out to keep the yeast alive while maximizing isobutanol production.The researchers started by putting a modified gene from a marine bacterium that is controllable by blue light into yeast's DNA. They then used light to turn on a chemical process that activates enzymes that naturally allow yeast to grow and multiply by eating glucose and secreting ethanol. But while those enzymes are active, ones that influence the production of isobutanol can't work. So the team turned to darkness to switch off the ethanol-producing enzymes to make room for the expression of their competitors."Normally light turns expression on," said Jared E. Toettcher, assistant professor of molecular biology and co-lead researcher, "but we also had to figure out how to make the absence of light turn another expression on."The challenge was to find the right balance of light and dark, given that yeast cells die when their natural fermentation process is disturbed, Zhao said: "The yeast get sick. They don't do anything anymore; they just stop."The researchers allowed the cells to grow by giving them bursts of blue light every few hours. In between they turned the light off to shift their metabolism from powering growth to producing isobutanol. Before the cells completely arrested, the researchers dispersed more bursts of light."Just enough light to keep the cells alive," said Toettcher, "but still crank out a whole lot of product that you want, which they produce only in the dark."Using light to control yeast's chemical production offers several advantages over techniques involving pure genetic engineering or chemical additives. For one, light is much faster and cheaper than most alternatives. It's also adjustable, meaning that turning it on and off can toggle the function of live cells on the spot at any point in the fermentation process (as opposed to chemicals, which generally can't be turned off once they are added.) Also, unlike chemical manipulators that diffuse throughout a cell, light can be applied to specific genes without affecting other parts of the cell.Optogenetics, as the use of light to control genes is called, is already used in neuroscience and other fields, but this the first application of the technology to control cellular metabolism for chemical production. Gregory Stephanopoulos, an MIT chemical engineering professor who was not involved with Princeton's research, called it a turning point in the field of metabolic engineering."It offers a brand new approach to the control of gene expression in microbial cultivation," Prof. Stephanopoulos said.The work and resulting paper were the culmination of interdisciplinary collaboration between Avalos's and Toettcher's labs.Both started working at Princeton in the winter of 2015 and immediately saw an opportunity to work together. Zhao worked in both labs."Within our first month we wanted to use light to control metabolic engineering," Toettcher said.Avalos said the researchers are working to improve their results. They have recently tested different colors of light to activate various proteins and cut the time needed for yeast to produce desired chemicals. But he said they would ultimately like to expand the scope of their work."We intend to keep pushing," Avalos said. "But metabolic engineering transcends industrial microbiology. It also allows us to study the metabolism of cells for health-related problems. You can control metabolism in any context, for industrial biology or to address medical questions."Other authors on the paper were Department of Chemical and Biological Engineering graduate students Yanfei Zhang, Justin Mehl, Helen Park, and Makoto A. Lalwani. Support for the project was provided in part by the Alfred P. Sloan Foundation, the National Institute of Health, the Pew Charitable Trusts and the Eric and Wendy Schmidt Transformative Technology Fund.
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March 21, 2018
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https://www.sciencedaily.com/releases/2018/03/180321094745.htm
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New genetic research shows extent of cross-breeding between wild wolves and domestic dogs
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Mating between domesticated dogs and wild wolves over hundreds of years has left a genetic mark on the wolf gene pool, new research has shown.
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The international study showed that around 60 per cent of Eurasian grey wolf genomes carried small blocks of the DNA of domestic dogs, suggesting that wolves cross-bred with dogs in past generations.The results suggest that wolf-dog hybridisation has been geographically widespread in Europe and Asia and has been occurring for centuries. The phenomenon is seen less frequently in wild wolf populations of North America.Researchers examined DNA data from grey wolves -- the ancestors of the domestic dog -- to determine how much their gene pool was diluted with the DNA of domestic canines, and how widespread the process of hybridisation is.Despite the evidence of hybridisation among Eurasian grey wolves, the wolf populations have remained genetically distinct from dogs, suggesting that such cross-breeding does not diminish distinctiveness of the wolf gene pool if it occurs at low levels.The results could have important conservation implications for the grey wolf, which is a keystone species -- meaning it is vital to the natural balance of the habitat it occupies. The legal status of hybrids is still uncertain and unregulated.The study was led by researchers from the University of Lincoln, UK, the Italian National Institute for Environmental Protection and Research and the University of California, Los Angeles.Dr Malgorzata Pilot, from the School of Life Sciences at the University of Lincoln, said: "The fact that wild wolves can cross-breed with dogs is well-documented, but little was previously known about how widespread this phenomenon has been and how it has affected the genetic composition of wild wolf populations."We found that while hybridisation has not compromised the genetic distinctiveness of wolf populations, a large number of wild wolves in Eurasia carry a small proportion of gene variants derived from dogs, leading to the ambiguity of how we define genetically 'pure wolves'."Our research highlighted that some individual wolves which had been identified as 'pure wolves' according to their physical characteristics were actually shown to be of mixed ancestry. On the other hand, two Italian wolves with an unusual, black coat colour did not show any genetic signatures of hybridisation, except for carrying a dog-derived variant of a gene linked to dark colouration. This suggests that the definition of genetically 'pure' wolves can be ambiguous and identifying admixed individuals can be difficult, implying that management strategies based on removal of suspected hybrids from wolf populations may be inefficient."Instead, our study has highlighted a need to reduce the factors which can cause hybridisation, such as abundance of free-ranging dogs, small wolf population sizes, and unregulated hunting."Studying a specific type of genetic variation in the DNA sequences of wolves and domestic dogs -- called Single Nucleotide Polymorphisms (SNPs) -- the scientists identified the transfer of dog gene variants into wolf genomes.A single DNA sequence is formed from a chain of four nucleotide bases and if some individuals in a population do not carry the same nucleotide at a specific position in the sequence, the variation is classified as an SNP.
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Genetically Modified
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March 20, 2018
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https://www.sciencedaily.com/releases/2018/03/180320141339.htm
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How obesity dulls the sense of taste
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Previous studies have indicated that weight gain can reduce one's sensitivity to the taste of food, and that this effect can be reversed when the weight is lost again, but it's been unclear as to how this phenomenon arises. Now a study publishing March 20 in the open-access journal
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A taste bud comprises of approximately 50 to 100 cells of three major types, each with different roles in sensing the five primary tastes (salt, sweet, bitter, sour, and umami). Taste bud cells turn over quickly, with an average lifespan of just 10 days. To explore changes in taste buds in obesity, the authors fed mice either a normal diet made up of 14% fat, or an obesogenic diet containing 58% fat. Perhaps unsurprisingly, after 8 weeks, the mice fed the obesogenic diet weigh about one-third more than those receiving normal chow. But strikingly, the obese mice had about 25% fewer taste buds than the lean mice, with no change in the average size or the distribution of the three cell types within individual buds.The turnover of taste bud cells normally arises from a balanced combination of programmed cell death (a process known as apoptosis) and generation of new cells from special progenitor cells. However, the researchers observed that the rate of apoptosis increased in obese mice, whereas the number of taste bud progenitor cells in the tongue declined, likely explaining the net decline in the number of taste buds. Mice that were genetically resistant to becoming obese did not show these effects, even when fed a high-fat diet, implying that they are due not to the consumption of fat per se, but rather the accumulation of fatty tissue (adipose).Obesity is known to be associated with a chronic state of low-grade inflammation, and adipose tissue produces pro-inflammatory cytokines -- molecules that serve as signals between cells -- including one called TNF-alpha. The authors found that the high-fat diet increased the level of TNF-alpha surrounding the taste buds; however mice that were genetically incapable of making TNF-alpha had no reduction in taste buds, despite gaining weight. Conversely, injecting TNF-alpha directly into the tongue of lean mice led to a reduction in taste buds, despite the low level of body fat."These data together suggest that gross adiposity stemming from chronic exposure to a high-fat diet is associated with a low-grade inflammatory response causing a disruption in the balancing mechanisms of taste bud maintenance and renewal," Dando said. "These results may point to novel therapeutic strategies for alleviating taste dysfunction in obese populations."
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Genetically Modified
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March 19, 2018
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https://www.sciencedaily.com/releases/2018/03/180319190054.htm
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Making intricate images with bacterial communities
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Working with light and genetically engineered bacteria, researchers from Stanford University are able to shape the growth of bacterial communities. From polka dots to stripes to circuits, they can render intricate designs overnight. The technique, described in the Mar. 19 in
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"Most of the bacteria on Earth live in biofilm communities and biofilms are very relevant in disease in health -- plaque on our teeth or catheter-based bacterial infection, for example," said Ingmar Riedel-Kruse, assistant professor of bioengineering and senior author of the paper. "Understanding how biofilms function is an important question on many levels."The group said the technique could clarify how biofilms grow and lead to the development of novel biomaterials or synthetic microbial communities that could be implemented in small devices or systems, such as microfluidic chips or biofilm-based circuits.The group's technique relies on E. coli bacteria they have genetically engineered to secrete a sticky protein in response to a particular wavelength of blue light. When they shine the appropriate wavelength light in the desired pattern on a culture dish of modified bacteria, the bacteria stick to the lit areas, forming a biofilm in the shape of the pattern. The researchers call their technique biofilm lithography for its similarity to lithography used in making electronic circuits.Other techniques for patterning bacterial communities exist, including depositing them with an inkjet printer or pre-patterning the culture surface with chemicals that bias bacterial growth in specific areas. However, biofilm lithography has the benefit of speed, simplicity, higher resolution and compatibility with a variety of surface environments including closed microfluidic devices, the researchers said.The intricate designs made possible with biofilm lithography could help in exploring the dynamics of bacterial communities."Biofilms exist in a social environment with other bacteria," said Xiaofan Jin, a graduate student in bioengineering and lead author of the paper. "Interactions between these bacteria are often dictated by where they grow relative to each other and this could be a great tool for specifying exactly when and where in a bacterial community certain species can live."While testing biofilm lithography, the researchers already happened upon a new insight. They had assumed that cells swimming in and out of illuminated regions would result in blurry patterns, but the designs turned out surprisingly sharp. These crisp images led the group to conclude that many of the bacteria must already be weakly bound to the culture surface. Rather than cruising around the dish, it appears that bacteria are continuously jumping on and off the surface."In the literature, there are different models of how certain bacterial species form biofilms," explained Riedel-Kruse. "We argue, at least with this species, that we provided additional evidence for that one hypothesis."By coincidence, the 25 micrometer resolution the researchers achieved with biofilms is similar to the first silicon photolithography, which contributed to the widespread success of silicon semiconductors. Similarly, the researchers see many versatile and impactful applications for their bacterial designs."We're hoping this tool can be applied toward further understanding bacterial communities, both natural and synthetic," said Jin. "We also see potential in having these communities do useful things, such as metabolic biosynthesis or distributed biocomputation. It may even be possible to create novel biomaterials such as conductive biofilm circuits."The researchers are currently taking steps to grow multiple strains of bacteria simultaneously through biofilm lithography to make multi-species communities. In particular, they hope to understand how bacteria in a biofilm may share antibiotic resistance -- a question with significant clinical implications, as biofilms are well-known for being stubborn against antibiotic treatment.Riedel-Kruse is also a member of Stanford Bio-X. This research was funded by Stanford Bio-X, the Natural Sciences and Engineering Research Council of Canada and the American Cancer Society.
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Genetically Modified
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March 12, 2018
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https://www.sciencedaily.com/releases/2018/03/180312150523.htm
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Forty years of data quantifies benefits of Bt corn adoption across multiple crops for the first time
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UMD researchers have pulled together forty years of data to quantify the effects of Bt field corn, a highly marketed and successful genetically engineered technology, in a novel and large-scale collaborative study. Other studies have demonstrated the benefits of Bt corn or cotton adoption on pest management for pests like the European corn borer or cotton bollworm in corn or cotton itself, but this is the first study to look at the effects on other offsite crops in North America. By tracking European corn borer populations, this study shows significant decreases in adult moth activity, recommended spraying regimens, and overall crop damage in vegetable crops such as sweet corn, peppers, and green beans. These benefits have never before been documented and showcase Bt crops as a powerful tool to reduce pest populations regionally thereby benefitting other crops in the agricultural landscape.
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Bt corn was first introduced and adopted in the United States in 1996 and is a genetically engineered crop (or GE) that makes up over 80% of our current corn plantings. In this study, Dr. Galen Dively, Professor Emeritus and Integrated Pest Management Consultant in the Department of Entomology, and Dr. Dilip Venugopal, UMD Research Associate, use data from 1976 -- 2016 to look at trends twenty years before and twenty years after adoption of Bt corn. "Safety of Bt corn has been tested extensively and proven, but this study is about effectiveness of Bt corn as a pest management strategy, and particularly benefits for offsite crops or different crops in different areas than the Bt field corn itself," explains Venugopal."This is the first paper published showing offsite benefits to other host plants for a pest like the corn borer, which is a significant pest for many other crops like green beans and peppers," says Dively. "We are seeing really more than 90 percent suppression of the European corn borer population in our area for these crops, which is incredible."Using numbers from pest traps to estimate the population and examine the recommended spraying regimens for pests like the European corn borer, Dively and Venugopal observed significant reductions in the population, with much less spraying occurring over time. "There would be no recommendation to spray for the corn borer given the current population, and this paper can trace that back to Bt corn adoption," said Dively. "What's more, by looking at the actual pest infestations and damage on actual crops over forty years of data, we took it a step farther to see the benefits on all sorts of crops and the declines in the actual pest population. We are able to see the results in theory and in practice on actual crops and in the real pest population over a long stretch of time.""The next steps would to be quantify the potentially millions of dollars in economic benefits we see here in a very concrete way to show money and time saved on spraying and pest management, crop damage reduction, as well as consideration of the environmental benefits. The important thing here, however, is to think of Bt crops as one of many tools in an integrated pest management tool box. The benefits are undeniable, but must always be weighed against many other options to use a broad range of tools and maximize benefit while minimizing any potential risks such as the pests developing Bt resistance," said Venugopal.Dively concludes, "This study ultimately shows the importance of evaluating GE crops beyond the field that is being planted. These products and the new advances coming down the pipeline have the potential to suppress major pest populations just like Bt corn has. This is just the beginning, and we need to be quantifying these effects. I am excited by these results and encouraged for future work."Their paper is published in the
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March 8, 2018
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https://www.sciencedaily.com/releases/2018/03/180308143102.htm
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The enemy within: Gut bacteria drive autoimmune disease
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Bacteria found in the small intestines of mice and humans can travel to other organs and trigger an autoimmune response, according to a new Yale study. The researchers also found that the autoimmune reaction can be suppressed with an antibiotic or vaccine designed to target the bacteria, they said.
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The findings, published in Gut bacteria have been linked to a range of diseases, including autoimmune conditions characterized by immune system attack of healthy tissue. To shed light on this link, a Yale research team focused on Enterococcus gallinarum, a bacterium they discovered is able to spontaneously "translocate" outside of the gut to lymph nodes, the liver, and spleen.In models of genetically susceptible mice, the researchers observed that in tissues outside the gut, Through further experiments, the research team found that they could suppress autoimmunity in mice with an antibiotic or a vaccine aimed at "When we blocked the pathway leading to inflammation, we could reverse the effect of this bug on autoimmunity," said senior author Martin Kriegel, M.D."The vaccine against While Kriegel and his colleagues plan further research on E. gallinarum and its mechanisms, the findings have relevance for systemic lupus and autoimmune liver disease, they said."Treatment with an antibiotic and other approaches such as vaccination are promising ways to improve the lives of patients with autoimmune disease," he said.
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Genetically Modified
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March 8, 2018
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https://www.sciencedaily.com/releases/2018/03/180308143052.htm
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Gene knockout using new CRISPR tool makes mosquitoes highly resistant to malaria parasite
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Deleting a single gene from mosquitoes can make them highly resistant to the malaria parasite and thus much less likely to transmit the parasite to humans, according to a new paper from scientists at Johns Hopkins Bloomberg School of Public Health's Malaria Research Institute.
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The scientists used the new CRISPR/Cas9 system, which permits precise DNA editing, to delete a gene called FREP1 from the genome of Anopheles gambiae mosquitoes, the chief transmitters of malaria to humans. Within the modified mosquitoes, malaria parasites were much less likely to survive and multiply. The CRISPR/Cas9 system used in this study was developed by Eric Marois, research scientist at the University of Strasbourg,The study, published March 8 in PLoS Pathogens, is the first to show that deleting a gene from mosquitoes can make them resistant to malaria parasites. It also underscores the potential of this strategy to modify wild mosquito populations and thereby reduce malaria transmission to humans.The CRISPR/Cas9 system is a set of DNA-editing molecules implicated in bacterial defense mechanism against viruses. In recent years, biologists have adapted it as a precise tool for genetic engineering -- in scientific experiments, and in prospective genetic-modification strategies against diseases such as malaria."Our study shows that we can use this new CRISPR/Cas9 gene-editing technology to render mosquitoes malaria-resistant by removing a so-called host factor gene," says study senior author George Dimopoulos, PhD, professor in the Bloomberg School's Department of Molecular Microbiology and Immunology. "This gives us a good technological platform for developing advanced malaria-control strategies, based on genetically modified mosquitoes unable to transmit the disease, and for studying the biology of malaria parasites in their mosquito hosts."The World Health Organization estimates there were more than 200 million cases of the disease in 2016 and more than 400,000 deaths, the majority occurring among children under age five in sub-Saharan Africa. A malaria vaccine is available, but its protection is only partial and temporary, and like antimalarial medicines, the vaccine has a limited supply. Researchers are turning to potentially cost-effective strategies that target malaria-carrying mosquitoes to prevent the spread of malaria in the first place.For the research, conducted in the insectary at the Johns Hopkins Malaria Research Institute in Baltimore, Dimopoulos and colleagues modified Anopheles gambiae mosquitoes by deleting the gene FREP1, which encodes an immune protein, fibrinogen-related protein 1. For reasons that aren't fully clear, the protein helps malaria parasites survive within the mosquito gut and progress to the developmental stages needed for their transmission to people. FREP1 is thus considered a malarial "host factor."The elimination of this host factor via the deletion of the FREP1 gene had other effects besides reducing the number of mosquitoes infected with malaria. After the FREP1 deletion, most of the modified mosquitoes had no evidence in their salivary glands of the sporozoite-stage parasites that enter the human bloodstream through a mosquito bite."The resistance to malaria parasites that's achieved by deleting FREP1 is remarkably potent," Dimopoulos says. "If you could successfully replace ordinary, wild-type mosquitoes with these modified mosquitoes, it's likely that there would be a significant impact on malaria transmission.Replacing ordinary mosquitoes in the wild with genetically modified mosquitoes hasn't yet been attempted, though scientists have been working on "gene drive" techniques that cause DNA modifications to spread quickly into a wild population via ordinary breeding. Gene drives use CRISPR/Cas9's DNA-editing ability to essentially hack the conception process, pushing a gene modification into all or nearly all the offspring of a modified animal. In 2016, for example, researchers reported that they had created a CRISPR/Cas9 gene drive that forces a fertility-reducing gene modification into female Anopheles gambiae mosquitoes -- which could quickly reduce local Anopheles populations if unleashed in the wild.In principle, the deletion or inactivation of FREP1 also could be incorporated in a gene drive system. Because it doesn't aim at reducing mosquitoes' health or ability to reproduce -- reducing "fitness" in the Darwinian sense -- a FREP1 inactivation would create less of an opportunity for mosquito mutations that resist its effects.Dimopoulos and his research team found that deleting FREP1 entirely from Anopheles did however come with some fitness costs to the modified mosquitoes. Compared to their wild-type cousins, the FREP1-less mosquitoes developed into adults more slowly, were less likely to take blood meals when given the opportunity and laid fewer and less viable eggs."We're now making mosquitoes in which FREP1 will be inactivated only in the adult gut," Dimopoulos says. "We predict that when we do that, the mosquito won't suffer the same fitness costs."In addition, he and his team are using their CRISPR/Cas9 DNA-editing platform to study the effects of deleting other potential malaria host-factor genes and to learn more about the roles of these host factors in mosquitoes. "We're focused not just on developing a malaria control strategy, but also learning more about the biology of malaria-carrying mosquitoes," Dimopoulos says.Support was provided by the National Institute of Allergy and Infectious Diseases, the Bloomberg Philanthropies, CNRS, Inserm, the University of Strasbourg, Agence Nationale de la Recherche, and the Johns Hopkins Malaria Research Institute.
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Genetically Modified
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March 6, 2018
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https://www.sciencedaily.com/releases/2018/03/180306115752.htm
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New method to improve crops
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A team of University of Georgia researchers has developed a new way to breed plants with better traits. By introducing a human protein into the model plant species
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Using this method to increase diversity among plant populations could serve to create varieties that are able to withstand drought or disease in crops or other plant populations, and the researchers have already begun testing the technique on maize, soy and rice.They published their findings in The research project was led by Lexiang Ji, a doctoral student in bioinformatics, and William Jordan, a doctoral student in genetics. The new method they explored, known as epimutagenesis, will make it possible to breed diverse plants in a way that isn't possible with traditional techniques."In the past this has been done with traditional breeding. You take a plant, breed it with another plant that has another characteristic you want to create another plant," said Jordan. "The problem with that is getting an individual that has all of the characteristics you want and none of the characteristics that you don't want. It's kind of difficult. With our new technique, you can modify how the genes are turned on and off in that plant without having to introduce a whole other set of genes from another parent."The idea for the method evolved originally from working in the lab with department of genetics professor Robert Schmitz, the corresponding author on the study. In his lab, researchers were studying DNA methylation, which controls expressed genetic traits, and creating maps of where DNA methylation is located in many plant species, including crops. When DNA methylation is removed, researchers found that they could selectively turn on previously silenced genes in the underlying genome of the plant."We saw repeatedly that lots of genes are silenced by DNA methylation and thought it was kind of curious," said Schmitz. "There are lots of discussions you can have about why these exist, but the reality is that they are there. So we wondered, how can we leverage them? Let's use the plant already in the field and reawaken some of those silenced genes to generate trait variation."To turn these dormant or silenced genes on, researchers introduced a human enzyme, known as a ten-eleven translocation enzyme, to plant seedlings using specially modified bacteria as a delivery vector. Introducing this human protein allows researchers to remove DNA methylation and thereby turn on previously silenced genes.Figuring out the best way to introduce the protein to the plant species has been a trial and error process. With Ji's expertise in bioinformatics, researchers are able to look at large sets of data about their experiment and make decisions on how to best proceed with the project."The data has really helped us brainstorm and coordinate what we should do next," said Ji. "That was particularly important in the beginning of this project because we just didn't know what was going to happen with this new technique.""Thousands of years ago you'd plant out hundreds of plants and one of them does really well so you'd breed out generations of that plant. Doing this though, you narrow down the genetic diversity until they're basically very, very similar," said Jordan. "While that's beneficial for yield or other plant characteristics that you might want, if there's a stress that they're not well adapted to because they're all so similar they're all going to respond in the same way. That creates a potentially vulnerable crop.""If they don't have the genetic differences to respond, then it can really wipe out crops," added Schmitz. "This isn't a savior, but it's an alternative strategy that has not been tried before. The idea is to access genes that people haven't been studying because they're not expressed but they're there. We think this method to reactivate these genes could lead to increased trait variation which could be useful for biotechnology applications."
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Genetically Modified
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March 1, 2018
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https://www.sciencedaily.com/releases/2018/03/180301144138.htm
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Mitochondria-to-nucleus messenger protein discovered
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Researchers have identified a protein, G-Protein Pathway Suppressor 2 (GPS2), that moves from a cell's mitochondria to its nucleus in response to stress and during the differentiation of fat cells. While proteins with similar functions had previously been found in yeast and worms, this is first direct messenger discovered in the cells of mammals.
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Mitochondria regulate cell survival and metabolism. They are often called the powerhouse of the cell because they take in oxygen and nutrients, break them down and create energy rich molecules for the cell. This is essential for cells and tissues to function properly and defects in mitochondrial functions and number are linked to aging and chronic diseases such as cancer, obesity, type II diabetes and neurological disorders.Mitochondria are special organelles that contain their own DNA. However, the information they store is not sufficient to sustain their own activity or biogenesis. Instead most of the genetic information for mitochondrial proteins is stored in the nuclear DNA. Thus, when the mitochondria are under stress they need to communicate with the nucleus so that it can respond appropriately to help restore their activity or increase in number.The researchers conducted their study in cell cultures and experimental models that had been genetically modified to lose the expression of GPS2. "Using a combination of imaging techniques, biochemical approaches and next-generation sequencing experiments, we were able to show that the total number of mitochondria in the cells and the fat tissue without GPS2 was considerably lower than in the normal ones. We also showed that in absence of GPS2, cells were not able to recover when exposed to mitochondrial stress," explained corresponding author Valentina Perissi, PhD, assistant professor of biochemistry at Boston University School of Medicine.Although these finding are primarily important for the basic understanding of cell biology and currently do not have direct translational implications, the ability to understand how mitochondria communicate their stress level and their energy status to the nucleus is an important step towards understanding of how mitochondrial diseases arise and how they can be treated. Also, therapeutic and lifestyle interventions designed for combating obesity and improving insulin sensitivity often rely on increased mitochondrial activity in the adipose tissue. Thus, a better understanding of the molecular mechanisms that regulate the biogenesis of mitochondria could have important translational implications.These findings appear online in the journal Funding for this study was provided by BNORC and BU/Joslin P&F Awards (P30DK046200, P30DK036836), F31DK108571 NRSA Predoctoral Fellowship and Research Grants R01DK100422 and DoD-BC160363.
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Genetically Modified
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February 27, 2018
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https://www.sciencedaily.com/releases/2018/02/180227090715.htm
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Scientists use forensic technology to genetically document infanticide in brown bears
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Scientists used a technology designed for the purposes of human forensics, to provide the first genetically documented case of infanticide in brown bears, following the murder of a female and her two cubs in Trentino, the Italian Alps, where a small re-introduced population has been genetically monitored for already 20 years.
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The study, conducted and authored by Francesca Davoli, The Italian Institute for Environmental Protection and Research (ISPRA), Bologna, and her team, is published in the open access journal To secure their own reproduction, males of some social mammalian species, such as lions and bears, exhibit infanticidal behaviour where they kill the offspring of their competitors, so that they can mate with the females which become fertile again soon after they lose their cubs. However, sometimes females are also killed while trying to protect their young, resulting in a survival threat to small populations and endangered species."In isolated populations with a small number of reproductive adults, sexually selected infanticide can negatively impact the long-term conservation of the species, especially in the case where the female is killed while protecting her cubs," point out the researchers."Taking this into account, the genetic identification of the perpetrators could give concrete indications for the management of small populations, for example, placing radio-collars on infanticidal males to track them," they add. "Nevertheless, genetic studies for identifying infanticidal males have received little attention."Thanks to a database containing the genotypes of all bears known to inhabit the study site and an open-source software used to analyse human forensic genetic profiles, the scientists were able to solve the case much like in a television crime series.Upon finding the three corpses, the researchers were certain that the animals had not been killed by a human. In the beginning, the suspects were all male brown bears reported from the area in 2015.Hoping to isolate the DNA of the perpetrator, the researchers collected three samples of hairs and swabbed the female's wounds in search for saliva. Dealing with a relatively small population, the scientists expected that the animals would share a genotype to an extent, meaning they needed plenty of samples.However, while the DNA retrieved from the saliva swabs did point to an adult male, at first glance it seemed that it belonged to the cubs' father. Later, the scientists puzzled out that the attacker must have injured the cubs and the mother alternately, thus spreading blood containing the inherited genetic material from the father bear. Previous knowledge also excluded the father, since there are no known cases of male bears killing their offspring. In fact, they seem to distinguish their own younglings, even though they most likely recognise the mother.To successfully determine the attacker, the scientists had to use the very small amount of genetic material from the saliva swabs they managed to collect and conduct a highly sophisticated analysis, in order to obtain four genetic profiles largely overlapping with each other. Then, they compared them against each of the males reported from the area that year. Eventually, they narrowed down the options to an individual listed as M7."The monitoring of litters is a fundamental tool for the management of bear populations: it has allowed the authors to genetically confirm the existence of cases of infanticide and in the future may facilitate the retrieval of information necessary to assess the impact of SSI on demographic trends," conclude the researchers.
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Genetically Modified
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February 19, 2018
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https://www.sciencedaily.com/releases/2018/02/180219155022.htm
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In living color: Brightly-colored bacteria could be used to 'grow' paints and coatings
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Researchers have unlocked the genetic code behind some of the brightest and most vibrant colours in nature. The paper, published in the journal
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The study is a collaboration between the University of Cambridge and Dutch company Hoekmine BV and shows how genetics can change the colour, and appearance, of certain types of brightly-coloured bacteria. The results open up the possibility of harvesting these bacteria for the large-scale manufacturing of nanostructured materials: biodegradable, non-toxic paints could be 'grown' and not made, for example.Flavobacterium is a type of bacteria that packs together in colonies that produce striking metallic colours, which come not from pigments, but from their internal structure, which reflects light at certain wavelengths. Scientists are still puzzled as to how these intricate structures are genetically engineered by nature, however."It is crucial to map the genes responsible for the structural colouration for further understanding of how nanostructures are engineered in nature," said first author Villads Egede Johansen, from Cambridge's Department of Chemistry. "This is the first systematic study of the genes underpinning structural colours -- not only in bacteria, but in any living system."The researchers compared the genetic information to optical properties and anatomy of wild-type and mutated bacterial colonies to understand how genes regulate the colour of the colony.By genetically mutating the bacteria, the researchers changed their dimensions or their ability to move, which altered the geometry of the colonies. By changing the geometry, they changed the colour: they changed the original metallic green colour of the colony in the entire visible range from blue to red. They were also able to create duller colouration or make the colour disappear entirely."We mapped several genes with previously unknown functions and we correlated them to the colonies' self-organisational capacity and their colouration," said senior author Dr Colin Ingham, CEO of Hoekmine BV."From an applied perspective, this bacterial system allows us to achieve tuneable living photonic structures that can be reproduced in abundance, avoiding traditional nanofabrication methods," said co-senior author Dr Silvia Vignolini from the Cambridge's Department of Chemistry. "We see a potential in the use of such bacterial colonies as photonic pigments that can be readily optimised for changing colouration under external stimuli and that can interface with other living tissues, thereby adapting to variable environments. The future is open for biodegradable paints on our cars and walls -- simply by growing exactly the colour and appearance we want!"
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Genetically Modified
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February 16, 2018
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https://www.sciencedaily.com/releases/2018/02/180216174738.htm
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Scientists shed light on biological roots of individuality
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Put 50 newborn worms in 50 separate containers, and they'll all start looking for food at roughly the same time. Like members of other species, microscopic
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It turns out that the innate system that controls age-appropriate behavior in a developing worm is not entirely dependable, however. Despite sharing identical genes and growing up in similar environments, some individual worms will inevitably march to the beat of their own drum.New research from Rockefeller University illuminates the biology that guides behavior across different stages of life, and also suggests how variations in specific neuromodulators in the developing nervous system may lead to occasional variations. The work, led by Cori Bargmann, is made possible by a newly engineered system that allows scientists to record behavioral information for individual worms over an entire lifecycle. It is published in "There are patterns at every stage of life that are different from the patterns at other stages, and with the system we created we can see that really clearly in ways that are surprisingly complex and robust," says Bargmann, who is the Torsten I. Wiesel Professor and head of the Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior. "We can also observe something as complex as individuality and start to break down the biology behind it."Our understanding of how genes govern behavior comes largely from experiments that involve altering a subject's normal state with external stimuli over a short period of time, such as giving a mouse some cheese as a reward for completing a maze. We know less about how genes affect behavior as animals go about their normal routines.Shay Stern, a postdoctoral associate in Bargmann's laboratory, engineered a system to capture spontaneous, internally-generated behavior in worms over the span of their entire development, which totals about 50 hours. The scientists focused on foraging behavior -- the worms' roaming movements in search for food -- and found incredibly similar patterns of activity between individuals."Even though the worms were separated and not receiving external cues, they were actively searching for food at the same time point in development as other worms," says Stern. "And we saw very precise differences in foraging behavior at each stage of development."By creating genetic mutations in some worms, the researchers were also able to identify specific neuromodulators, or chemical messengers in the brain, that normally keep the animals on schedule. A mutation that disrupted the chemical messenger dopamine, for example, affected the worms' roaming speed during late development. Other mutations affected behavioral patterns within each developmental stage, suggesting that different neuromodulators influence behavior over different timescales.While the majority of worms conformed to the same behavioral patterns, a number of individual worms stood out for their atypical foraging behaviors. Variability between individuals is typically attributed to genetic differences or exposure to different environments, but the researchers designed this study to account for these differences, using genetically identical worms in identical environments.One explanation for these individual variations could be small differences in how the nervous system develops. There is a randomness factor in how some neurons connect with each other that isn't controlled by genetics, notes Bargmann.But Bargmann and colleagues showed that neuromodulators can also contribute. The researchers found that removing the chemical messenger serotonin from a population of worms drastically reduced the number of worms that displayed unique roaming patterns, or individuality. Indeed, without serotonin, all of the worms exhibited the same foraging behavior at the same time -- a finding that suggests how important individuality is to survival."From an evolutionary point of view, we can't have everyone going off the cliff all at once like lemmings -- someone's got to be doing something different for a species to survive," says Bargmann.
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Genetically Modified
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February 15, 2018
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https://www.sciencedaily.com/releases/2018/02/180215105723.htm
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Scientists improve DNA transfer in gene therapy
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Parkinson's disease, Huntington's disease, cystic fibrosis -- these and many other fatal hereditary human diseases are genetically transmitted. Many cancers and cardiovascular diseases are also caused by genetic defects. Gene therapy is a promising possibility for the treatment of these diseases. With the help of genetically modified viruses, DNA is introduced into cells in order to repair or replace defective genes. By using this method, scientists from the German Primate Center (DPZ) -- Leibniz Institute for Primate Research have discovered a quicker and more efficient treatment for the cells. For this purpose, the scientists changed the so-called HEK293 cell line that is used for the production of therapeutic viruses. The cells then produced a protein called CD9 in large quantities. In addition, they modified the viruses used for gene transfer in such a way that CD9 is integrated into their envelope membrane. These genetic manipulations resulted in a faster and more efficient infection of the target cells. The resulting higher transfer rate of DNA into the target cells promises new and improved gene therapy treatment. The study was published in the journal
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The ability of viruses to introduce their genetic material into the host cells is used as a tool in gene therapy. These "gene taxis" consist of modified viruses, the so-called viral vectors. They are equipped with fully functional genes to replace the defective disease-causing genes in the cells. However, the prerequisite for this is that the viruses recognize and infect the corresponding cells. This is the point where the research of the junior research group Medical RNA Biology at the German Primate Center comes in."In our study, we wanted to find out if it was possible to improve the infection rate of viral vectors and how," says Jens Gruber, head of the junior research group and senior author of the study. "At the moment, the infection rates, depending on the target cells, are often around 20 percent, which is not enough for certain therapies." To change that, the researchers looked at the production of the so-called exosomes to find out how to use this mechanism in order for the virus vectors to become more efficient. Exosomes are small membrane vesicles filled with proteins, RNA or other molecules. They are used for the transportation of cell components and for intercellular communication. "Our hypothesis was that we could improve the production of viruses and their efficiency by boosting exosome production in the cells," explains Jens Gruber explaining the relevance of the transport vesicles for the study.In order to produce large quantities of the CD9 protein, Jens Gruber and his team genetically engineered the HEK293 cell lines that are used for the production of viral vectors. This protein is known for its function in cell movement, cell-cell contact, and membrane fusion. The assumption was that it could also play a role in exosome production. In addition, scientists incorporated the CD9 protein into the envelope membrane of viral vectors. "We were able to observe two things," Jens Gruber summarizes the results. "Firstly, in comparison to the untreated HEK293 cells, exosome production in the HEK293-CD9 cells increased significantly, which suggests a crucial role of the protein in exosome formation. Secondly, the incorporation of the CD9 protein in the viral membrane has significantly improved the transfer of DNA. This was observed in an increased number of infected target cells that carried the desired gene without the implementation of additional virus vectors."The increased amount of CD9 in the virus resulted in a higher infection rate that amounted to approximately 80 percent. The protein appears to have a direct impact on exosome production and virus efficiency, which has previously not been described. "The results of our study provide us with a better understanding of exosome formation as well as virus production in cells," says Jens Gruber. "These findings can be used to make currently used virus-based gene therapies more efficient. In future, one might be able to completely abstain from using viruses and only use exosomes to transport genetic material into target cells."
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Genetically Modified
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February 12, 2018
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https://www.sciencedaily.com/releases/2018/02/180212100618.htm
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Mouse study adds to evidence linking gut bacteria and obesity
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A new Johns Hopkins study of mice with the rodent equivalent of metabolic syndrome has added to evidence that the intestinal microbiome -- a "garden" of bacterial, viral and fungal genes -- plays a substantial role in the development of obesity and insulin resistance in mammals, including humans.
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A report of the findings, published Jan. 24 in "This study adds to our understanding of how bacteria may cause obesity, and we found particular types of bacteria in mice that were strongly linked to metabolic syndrome," says David Hackam, M.D., Ph.D., surgeon-in-chief and co-director of Johns Hopkins Children's Center and the study's senior author. "With this new knowledge we can look for ways to control the responsible bacteria or related genes and hopefully prevent obesity in children and adults."Metabolic syndrome, a cluster of conditions including obesity around the waist, high blood sugar and increased blood pressure, is a risk factor for heart disease, stroke and diabetes. While no precise cause for metabolic syndrome is known, previous studies of Toll-like receptor 4 (TLR4), a protein that receives chemical signals to activate inflammation, have suggested that TLR4 may be responsible in part for its development.How and why TLR4 may be responsible for metabolic syndrome, however, has been unclear, says Hackam. Perhaps, the research team thought, TLR4 signaling in different cells and their association with the bacterial environment could result in different effects on the development of metabolic syndrome.To first determine whether TLR4 specifically in the intestinal epithelium (layer of cells that line the small and large intestines) would cause the development of metabolic syndrome, the research team ran a series of experiments on both normal mice and mice genetically modified to lack TLR4 in their intestinal epithelium.The researchers fed both groups of mice "standard chow," or food with 22 percent fat calories, for 21 weeks.Compared to normal mice, those lacking TLR4 showed a series of symptoms consistent with metabolic syndrome, such as significant weight gain, increased body and liver fat, and insulin resistance.The researchers then fed both groups of mice a high-fat diet composed of 60 percent fat calories for 21 weeks to find out whether diet would affect the development of metabolic syndrome. Again, the genetically modified mice gained significantly more in weight and had greater body and liver fat than the normal mice.To confirm the role of TLR4 expression in the intestinal epithelium, the researchers genetically modified three more groups of mice: one group expressed TLR4 only in the intestinal epithelium, another group lacked TLR4 in all body cells and the third group lacked TLR4 only in white blood cells.All groups ate standard chow, and all groups had similar body weight, body and liver fat, and glucose tolerance compared to normal mice. Compared with normal mice, belly and small intestine fat was higher in mice lacking TLR4 only in the intestinal epithelium. This, the researchers say, provides further evidence that deleting TLR4 specifically from the intestinal epithelium is required for developing metabolic syndrome.To investigate the role the bacterial makeup of the gut had on the mice, Hackam and his team then administered antibiotics to the normal and TLR4 intestinal epithelium-deficient mice. Antibiotics significantly reduced the amount of bacteria in the intestinal tract and prevented all symptoms of metabolic syndrome in the mice that lacked TLR4 in their intestinal epitheliums.This demonstrates, the researchers say, that bacterial levels can be manipulated to prevent the development of metabolic syndrome.To further explore the role of intestinal epithelial TLR4 on the development of metabolic syndrome, the research team analyzed fecal samples from the TLR4 intestinal epithelium-deficient and normal mice. The team found that specific clusters of bacteria that contribute to the development of metabolic syndrome were expressed differently in the deficient mice than in normal mice. They also determined that the bacteria expressed genes that made them "less hungry" and thus less able to digest the nutrients present in the mouse chow. This resulted in a greater abundance of food for the mouse to absorb, which contributed to obesity.The researchers then analyzed the genes expressed in the lining of the intestinal mucosa -- the site at which food absorption occurs -- in normal and TLR4 intestinal epithelium-deficient mice. Of note, the team determined that important genes in the perixisome proliferator-activated receptor (PPAR) metabolic pathway were significantly suppressed in the deficient mice. Administering antibiotics prevented the differences in gene regulation between the two groups of mice, as did administering drugs to activate the PPAR signaling pathway, further explaining the reasons for which obesity developed."All of our experiments imply that the bacterial sensor TLR4 regulates both host and bacterial genes that play previously unrecognized roles in energy metabolism leading to the development of metabolic syndrome in mice," says Hackam.
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Genetically Modified
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February 9, 2018
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https://www.sciencedaily.com/releases/2018/02/180209170526.htm
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Efficient technique discovered for isolating embryonic stem cells in cows
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For more than 35 years, scientists have tried to isolate embryonic stem cells in cows without much success. Under the right conditions, embryonic stem cells can grow indefinitely and make any other cell type or tissue, which has huge implications for creating genetically superior cows.
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In a study published this week in the journal Producing embryonic stem cells from large livestock species like cattle is important for genetic testing, genome engineering and studying human disease. The cells may offer a better model for human stem cell therapies. Mice and rats are sometimes too small to demonstrate whether certain therapies will work on humans.If researchers can generate gametes, or sperm and eggs cells, from the stem cell lines, the ramifications are profound. Such "in vitro" breeding could decrease the amount of time it takes to produce genetically superior cattle."That could revolutionize the way we do genetics by orders of magnitude," said study author Pablo Ross, an associate professor in the Department of Animal Science at UC Davis' College of Agricultural and Environmental Sciences.In just a few years, scientists could speed up the process of improving generations by decades. "In two and a half years, you could have a cow that would have taken you about 25 years to achieve. It will be like the cow of the future. It's why we're so excited about this," said Ross.The cow of the future could have more muscle, produce more milk, emit less methane, or more easily adapt to a warmer climate.Ross envisions the findings helping the cattle industry become more sustainable. "Animals that are more efficient and have improved welfare, that may have more disease resistance is better for everyone," said Ross.
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Genetically Modified
| 2,018 |
February 6, 2018
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https://www.sciencedaily.com/releases/2018/02/180206100331.htm
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Workbench for virus design
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Bacteriophages, known informally as phages, are viruses that can attack and kill specific bacteria. They occur everywhere in the natural world. Precisely because they are matched to just one specific type of bacteria, researchers and medics hope that phages can be engineered to combat certain bacterial infections. For example, the food industry is already using these phages to destroy pathogens in food products by natural methods.
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However, genetically engineering phages in order to customise them for specific applications continues to be a very challenging and time-consuming process. It is particularly difficult to modify phages to combat Gram-positive bacteria such as A new era may now be dawning in the use of bacteriophages, however, as a team of researchers led by Martin Loessner, Professor of Food Microbiology at ETH Zurich, has just presented a novel technology platform in a paper published in the journal The new phage workbench allows such viruses to be created very quickly and the "toolbox" is extremely modular: it allows the scientists to create almost any bacteriophages for different purposes, with a great variety of functions."Previously it was almost impossible to modify the genome of a bacteriophage," Loessner says. On top of that, the methods were very inefficient. For example, a gene was only integrated into an existing genome in a tiny fraction of the phages. Isolating the modified phage was therefore often like searching for a needle in a haystack."In the past we had to screen millions of phages and select those with the desired characteristics. Now we are able to create these viruses from scratch, test them within a reasonable period and if necessary modify them again," Loessner stresses.Samuel Kilcher, a specialist in molecular virology, has played a key role in the breakthrough: he used synthetic biology methods to plan the genome of a bacteriophage on the drawing board and assemble it in a test tube from DNA fragments. At the same time new, additional functions were incorporated in the phage genome, such as enzymes to dissolve the bacterial cell wall. In addition, Kilcher is able to remove genes that give a phage unwanted properties, such as the integration into the bacterial genome or the production of cytotoxins.In order to reactivate a phage from synthetic DNA, the genome was introduced into spherical, cell wall-deficient but viable forms of the Listeria bacterium (L-form Listeria). Based on the genetic blueprint, these bacterial cells then produce all the components of the desired phage and ensure that the virus particles are assembled correctly.The researchers also discovered that spherical Listeria cells are not only capable of creating their own specific phages, but also those able to attack other bacteria. Usually, a host only generates its own specific viruses. L-form Listeria are therefore suitable as a virtually universal incubator for bacteriophages.If the Listeria cells are then brought to the point where they rupture (lysis), the bacteriophages are released and can be isolated and multiplied for use in therapy or diagnostics."A key prerequisite for using effective synthetic bacteriophages is that their genome is unable to integrate into the host's genome," Kilcher emphasises. If this happens, the virus no longer presents a threat to the bacterium. Using this new method, however, the scientists were able to simply reprogram such integrative phages so that they become interesting again for antibacterial applications.The two researchers are not particularly worried about potential resistances against the phages. And even if there were any, for example due to a bacterium changing its surface structures to prevent the virus from attaching, the new technology makes it possible to develop a suitable phage against which a bacterium has not yet developed resistance.The researchers also think the danger of unintended release is very small: because the bacteriophages -- both natural and synthetic -- are extremely host-specific, they cannot survive for long without their host. This high specificity also prevents the bacteriophages from switching to a new host bacterium. "Adapting to the surface structure of a different host would take an awful long time in nature," Loessner says.With this new technology, Loessner's team has made a giant stride towards applying synthetic bacteriophages for use in therapy, diagnostics or the food industry. The scientists are thus managing to overcome constraints associated with the use of naturally occurring phages. "Our toolbox could help to exploit the potential of phages," Loessner says. The researchers have applied for a patent for their technology. Now they hope to find licensees to produce the phages for therapy and diagnostics.
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January 31, 2018
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https://www.sciencedaily.com/releases/2018/01/180131184751.htm
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Cancer 'vaccine' eliminates tumors in mice
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Injecting minute amounts of two immune-stimulating agents directly into solid tumors in mice can eliminate all traces of cancer in the animals, including distant, untreated metastases, according to a study by researchers at the Stanford University School of Medicine.
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The approach works for many different types of cancers, including those that arise spontaneously, the study found.The researchers believe the local application of very small amounts of the agents could serve as a rapid and relatively inexpensive cancer therapy that is unlikely to cause the adverse side effects often seen with bodywide immune stimulation."When we use these two agents together, we see the elimination of tumors all over the body," said Ronald Levy, MD, professor of oncology. "This approach bypasses the need to identify tumor-specific immune targets and doesn't require wholesale activation of the immune system or customization of a patient's immune cells."One agent is currently already approved for use in humans; the other has been tested for human use in several unrelated clinical trials. A clinical trial was launched in January to test the effect of the treatment in patients with lymphoma.Levy, who holds the Robert K. and Helen K. Summy Professorship in the School of Medicine, is the senior author of the study, which will be published Jan. 31 in Levy is a pioneer in the field of cancer immunotherapy, in which researchers try to harness the immune system to combat cancer. Research in his laboratory led to the development of rituximab, one of the first monoclonal antibodies approved for use as an anticancer treatment in humans.Some immunotherapy approaches rely on stimulating the immune system throughout the body. Others target naturally occurring checkpoints that limit the anti-cancer activity of immune cells. Still others, like the CAR T-cell therapy recently approved to treat some types of leukemia and lymphomas, require a patient's immune cells to be removed from the body and genetically engineered to attack the tumor cells. Many of these approaches have been successful, but they each have downsides -- from difficult-to-handle side effects to high-cost and lengthy preparation or treatment times."All of these immunotherapy advances are changing medical practice," Levy said. "Our approach uses a one-time application of very small amounts of two agents to stimulate the immune cells only within the tumor itself. In the mice, we saw amazing, bodywide effects, including the elimination of tumors all over the animal."Cancers often exist in a strange kind of limbo with regard to the immune system. Immune cells like T cells recognize the abnormal proteins often present on cancer cells and infiltrate to attack the tumor. However, as the tumor grows, it often devises ways to suppress the activity of the T cells.Levy's method works to reactivate the cancer-specific T cells by injecting microgram amounts of two agents directly into the tumor site. (A microgram is one-millionth of a gram). One, a short stretch of DNA called a CpG oligonucleotide, works with other nearby immune cells to amplify the expression of an activating receptor called OX40 on the surface of the T cells. The other, an antibody that binds to OX40, activates the T cells to lead the charge against the cancer cells. Because the two agents are injected directly into the tumor, only T cells that have infiltrated it are activated. In effect, these T cells are "prescreened" by the body to recognize only cancer-specific proteins.Some of these tumor-specific, activated T cells then leave the original tumor to find and destroy other identical tumors throughout the body.The approach worked startlingly well in laboratory mice with transplanted mouse lymphoma tumors in two sites on their bodies. Injecting one tumor site with the two agents caused the regression not just of the treated tumor, but also of the second, untreated tumor. In this way, 87 of 90 mice were cured of the cancer. Although the cancer recurred in three of the mice, the tumors again regressed after a second treatment. The researchers saw similar results in mice bearing breast, colon and melanoma tumors.Mice genetically engineered to spontaneously develop breast cancers in all 10 of their mammary pads also responded to the treatment. Treating the first tumor that arose often prevented the occurrence of future tumors and significantly increased the animals' life span, the researchers found.Finally, Sagiv-Barfi explored the specificity of the T cells by transplanting two types of tumors into the mice. She transplanted the same lymphoma cancer cells in two locations, and she transplanted a colon cancer cell line in a third location. Treatment of one of the lymphoma sites caused the regression of both lymphoma tumors but did not affect the growth of the colon cancer cells."This is a very targeted approach," Levy said. "Only the tumor that shares the protein targets displayed by the treated site is affected. We're attacking specific targets without having to identify exactly what proteins the T cells are recognizing."The current clinical trial is expected to recruit about 15 patients with low-grade lymphoma. If successful, Levy believes the treatment could be useful for many tumor types. He envisions a future in which clinicians inject the two agents into solid tumors in humans prior to surgical removal of the cancer as a way to prevent recurrence due to unidentified metastases or lingering cancer cells, or even to head off the development of future tumors that arise due to genetic mutations like BRCA1 and 2."I don't think there's a limit to the type of tumor we could potentially treat, as long as it has been infiltrated by the immune system," Levy said.The work is an example of Stanford Medicine's focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.
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January 22, 2018
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https://www.sciencedaily.com/releases/2018/01/180122150742.htm
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Digging deep into distinctly different DNA
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A University of Queensland discovery has deepened our understanding of the genetic mutations that arise in different tissues, and how these are inherited.
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Researchers from UQ's Queensland Brain Institute, led by Dr Steven Zuryn, found the rates of genetic mutations in mitochondrial DNA vary across differing tissue types, with the highest rate occurring in reproductive cells."Mitochondria are known as the cell's power plant -- they are found in all animal and human cells -- and in humans they generate about 90 per cent of the body's energy from the food we eat and the oxygen we breathe," Dr Zuryn said."In addition to regular DNA, which is contained in the nucleus, each cell also contains DNA in the mitochondria."Mitochondrial DNA is only passed down from the mother's side, and transmits the genetic information from one generation to the next."The team studied the transparent roundworm ("The researchers developed an exceptionally pure method of isolating mitochondria from specific cells in the body to study them in detail."We now suspect that there is a mechanism in all animals that can filter out these mutations before they are passed to future offspring, which could otherwise cause a multitude of diseases affecting the brain," Dr Zuryn said.In humans, mutations in mitochondrial DNA can cause rare but devastating diseases, especially in organs such as the brain, which relies heavily on mitochondria for energy.The study is published in The research was supported by the Stafford Fox Medical Research Foundation and the National Health and Medical Research Council.
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January 22, 2018
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https://www.sciencedaily.com/releases/2018/01/180122104047.htm
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Combination of resistance genes offers better protection for wheat against powdery mildew
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A decent wheat harvest requires robust wheat. However, wheat crops are often infected by fun-gal diseases such as powdery mildew. For several years now, UZH researchers have been inves-tigating a wheat gene that confers resistance to powdery mildew (
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The researchers created new wheat lines by crossbreeding transgenic Pm3 lines (see box). This resulted in four new wheat lines, each containing two different Pm3 gene variations. "These four new wheat lines showed improved resistance against powdery mildew in field trials compared with their parental lines -- during the field seasons 2015 to 2017," explains Teresa Koller, lead author of the study.Back in the laboratory, the scientists proved that the parental lines' gene activity is added up in the newly created lines. Each Pm3 allele in the four new lines displayed the same activity as in the parental line, which results in increased overall activity, since it came from two different gene variations. "The improved resistance against powdery mildew is the result of the increased total transgene activity as well as the combination of the two Pm3 gene variations," summarizes Teresa Koller. The high overall activity of resistance genes did not cause any negative effects for the development of the wheat or its yield.The findings of these trials improve our general knowledge of the immune system of plants, and in particular of fungal disease resistance of wheat. Besides contributing to fundamental research in the area of plants' immune systems, the findings can also be applied in wheat breeding. Thanks to the precise testing of Pm3 alleles, the best variations and combinations are identified and can then be used directly in traditional breeding by crossbreeding them into modern wheat varieties.The Pm3 gene is the "blueprint" for a protein that can receive signals in the plant cell, i.e. a receptor. It is able to recognize avirulent proteins, or AvrPm3 for short, of the powdery mildew fungus. The receptor triggers the plant cell's death as soon as the harmful fungus attempts to inject the AvrPm3 protein into the plant cell. By killing off the attacked cell, the rest of the plant is protected against the fungus. Different Pm3 gene variations, or Pm3 alleles, encode different variations of the receptor. These receptor variations are able to recognize different AvrPm3 proteins of the powdery mildew fungus.Prof. Beat Keller and his team have identified various Pm3 gene variations in powdery mildew-resistant wheat varieties from across the world. To assess the function and effectiveness of the different Pm3 gene variations, they were genetically engineered into the genome of the spring wheat variety Bobwhite. Bobwhite wheat lacks its own functioning Pm3 gene and is very sus-ceptible to powdery mildew. The transgenic Bobwhite wheat lines, each containing a single Pm3 gene variation, were assessed in field trials as part of the National Research Program NFP59 between 2008 and 2010. The findings of these trials were published in 2011 and 2012.
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January 18, 2018
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https://www.sciencedaily.com/releases/2018/01/180118142532.htm
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Crop failure in the Andes
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Kenneth Feeley, the Smathers Chair of Tropical Tree Biology in the University of Miami's Department of Biology, is an expert in studying the effects of climate change on tropical forests. From the mountains of Peru to the lowlands of the Amazon, Feeley examines the ramifications of climate change on the trees and other species that comprise the diverse forests of these regions. Yet, recently, Feeley shifted gears from studying tropical forests to examining the impacts of climate change in rural farming communities in Peru.
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As co-author of a study published in "The research was executed in a very remote part of Peru," said Feeley. "We were trying to look at how the traditional agriculture practices of people in the high Andes Mountains will be impacted by climate change so we performed a set of experiments to simulate different scenarios under global warming."In the first experiment, the researchers simulated what will happen if farmers continue cultivating the same areas amid rising temperatures. To do this, they grew corn farther down the mountain, where temperatures are slightly higher. "We carried in the soil from where the corn is normally grown because the soil at the top of the mountain is different in texture and nutrients than the soil at lower elevations," said Feeley.The simulation revealed that, with just a small temperature increase of 1.3 degrees to 2.6 degrees, nearly all the corn plants were killed by invading birds and pest insects. Potato plants fared even worse. When potatoes were grown at lower elevations (but in their normal soil), most of the plants died and any potatoes that survived were of such low quality they had no market value.In a second set of experiments, the researchers simulated what will happen if farmers try to counteract rising temperatures by moving their corn farms to higher elevations. (Potato crops are already grown along mountain peaks, so moving those farms higher isn't an option.) To accomplish this simulation, the researchers grew corn under normal temperatures but in soils carried in from higher elevations. When grown at a higher elevation, the corn plants survived but the quality and quantity of the harvest was greatly reduced."We found big decreases in the yield, quality, and the market value of the corn and potatoes planted under these simulated future conditions," said Feeley. "Notably, much of the decline was due to increased damage by pests, something that is often not taken into account in greenhouse or lab studies. Given the extreme importance of these staple crops for Andean communities, our findings can have huge, and scary, implications."The study measured the crops during a growing season within the remote Huamburque area of the Andean Amazon basin, where elevations range between 3,000 and 4,000 meters. Unfortunately, Feeley said, farmers in this rural area of Peru lack the means to purchase genetically modified varieties of corn or potato, as well as pesticides to remove the pests or commercial fertilizers."Small communities in rural places don't have the technology or market access to quickly adapt to climate change," said Feeley. "Some farmers might be able to switch their crop to a variety that is tolerant to higher temperatures, but many lack the resources to save their crops by using irrigation pumps or fertilizers. These farmers are in jeopardy as are millions of people who depend on these crops throughout the Andes of Colombia, Ecuador, and Bolivia."
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January 15, 2018
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https://www.sciencedaily.com/releases/2018/01/180115120555.htm
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Fast-tracking T-cell therapies with immune-mimicking biomaterials
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Immunologists and oncologists are harnessing the body's immune system to fight cancers and other diseases with adoptive cell transfer techniques. In a normal immune response, a type of white blood cell known as T cells are instructed by another kind of immune cell called an antigen-presenting cell (APC) to expand their numbers and stay alive. Adoptive cell transfer procedures are mimicking exactly this process in a culture dish by taking T cells from patients, multiplying them, sometimes genetically modifying them, and then returning them to patients so that they can, for example, locate and kill cancer cells. However, these procedures often take weeks to produce batches of therapeutic T cells that are large and reactive enough to be able to eliminate their target cells.
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A team led by David Mooney at Harvard's Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS) is now reporting in "Our approach closely mimics how APCs present their stimulating cues to primary T cells on their outer membrane and how they release soluble factors that enhance the survival of the T cells. As a result, we achieve much faster and greater expansion. By varying the compositions of lipids, cues, and diffusible factors in the scaffolds, we engineered a very versatile and flexible platform that can be used to amplify specific T cell populations from blood samples, and that could be deployed in existing therapies such as CAR-T cell therapies," said Mooney, Ph.D., a Core Faculty member at the Wyss Institute and leader of its Immunomaterials Platform. Mooney is also the Robert P. Pinkas Family Professor of Bioengineering at SEAS.To engineer an APC-mimetic scaffold, the team first loaded tiny mesoporous silica rods (MSRs) with Interleukin 2 (IL-2) -- an APC-produced factor that prolongs the survival of associated T cells. The MSRs were then coated with lipids that formed a thin supported lipid bilayer (SLB), which resembles the outer membrane of APCs and that the researchers then functionalized with a pair of T cell-stimulating antibodies that remain mobile in the lipid layer and can bind to receptor/co-receptor molecules on the surface of T cells. In culture medium, 3D scaffolds spontaneously formed through the settling and random stacking of the rods, forming pores big enough to allow the entry, movement, and accumulation of T cells, thereby signaling them to multiply.In a series of side-by-side comparisons, Mooney's team demonstrated that APC-mimetic scaffolds performed better than methods involving commercially available expansion beads (Dynabeads), which are currently used in clinical adoptive cell transfer approaches. "In a single dose, APC-mimetic scaffolds led to two- to ten-fold greater expansion of primary mouse and human T cells than Dynabeads. As another advantage, APC-mimetic scaffolds enabled us to tune the ratios of subpopulations of T cells with different roles in the desired immune responses, which in the future might increase their functionality," said David Zhang, the study's second author and a Graduate Student working with Mooney.Building on these findings, the researchers demonstrated the utility of their T cell expansion platform in a therapeutic model. "Prompted by recent breakthroughs in CAR-T cell therapies, we showed that a specific CAR-T cell product expanded with an APC-mimetic scaffold could facilitate treatment of a mouse model of a human lymphoma cancer," said first author Alexander Cheung, Ph.D., who started the project in Mooney's team and now is a scientist at UNUM Therapeutics in Cambridge, Massachusetts. An APC-mimetic scaffold that was engineered to activate a specific type of CAR-T cell was able to generate higher numbers of the modified T cells over longer periods of culture than analogously designed expansion beads, and the resulting cells were similarly effective in killing the lymphoma cells in the mice.After successfully using the material to expand all T cells present in a sample, the team demonstrated that APC-mimetic scaffolds could also be used to expand antigen-specific T cell clones from a more complex mixture of cells. Such T cell clones are constantly developed by the immune system to recognize small specific peptides contained in foreign proteins. To this aim, the researchers incorporated molecules into the scaffolds that are known as the major histocompatibility complex (MHC) and that presented small peptides derived from viral proteins to T cells."Based also on studies in which we showed that APC-mimetic scaffolds also have superior potential to specifically enrich and expand rare T cell sub-populations from blood, we strongly believe that we created an effective platform technology that could facilitate more effective precision immunotherapies," said Cheung."The bioinspired T cell-activating scaffolds developed by the Wyss Institute's Immunomaterials Platform could accelerate the success of many immunotherapeutic approaches in the clinic, with life-saving impact on a broad range of patients, in addition to advancing personalized medicine," 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.In addition, Sandeep Koshy, Ph.D., who worked as a Graduate Student on Mooney's team and now is an Immuno-oncology Researcher at the Novartis Institutes for BioMedical Research in Cambridge, Mass., is an author on the study. The work was supported by the Wyss Institute for Biologically Inspired Engineering at Harvard University, the National Institutes of Health, and the National Science Foundation.
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January 12, 2018
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https://www.sciencedaily.com/releases/2018/01/180112095938.htm
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New technology will create brain wiring diagrams
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The human brain is composed of billions of neurons wired together in intricate webs and communicating through electrical pulses and chemical signals. Although neuroscientists have made progress in understanding the brain's many functions -- such as regulating sleep, storing memories, and making decisions -- visualizing the entire "wiring diagram" of neural connections throughout a brain is not possible using currently available methods. But now, using Drosophila fruit flies, Caltech researchers have developed a method to easily see neural connections and the flow of communications in real time within living flies. The work is a step forward toward creating a map of the entire fly brain's many connections, which could help scientists understand the neural circuits within human brains as well.
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A paper describing the work appears online in the December 12 issue of "If an electrical engineer wants to understand how a computer works, the first thing that he or she would want to figure out is how the different components are wired to each other," says Lois. "Similarly, we must know how neurons are wired together in order to understand how brains work."When two neurons connect, they link together with a structure called a synapse, a space through which one neuron can send and receive electrical and chemical signals to or from another neuron. Even if multiple neurons are very close together, they need synapses to truly communicate.The Lois laboratory has developed a method for tracing the flow of information across synapses, called TRACT (Transneuronal Control of Transcription). Using genetically engineered Drosophila fruit flies, TRACT allows researchers to observe which neurons are "talking" and which neurons are "listening" by prompting the connected neurons to produce glowing proteins.With TRACT, when a neuron "talks" -- or transmits a chemical or electrical signal across a synapse -- it will also produce and send along a fluorescent protein that lights up both the talking neuron and its synapses with a particular color. Any neurons "listening" to the signal receive this protein, which binds to a so-called receptor molecule -- genetically built-in by the researchers -- on the receiving neuron's surface. The binding of the signal protein activates the receptor and triggers the neuron it's attached to in order to produce its own, differently colored fluorescent protein. In this way, communication between neurons becomes visible. Using a type of microscope that can peer through a thin window installed on the fly's head, the researchers can observe the colorful glow of neural connections in real time as the fly grows, moves, and experiences changes in its environment.Many neurological and psychiatric conditions, such as autism and schizophrenia, are thought to be caused by altered connections between neurons. Using TRACT, scientists can monitor the neuronal connections in the brains of hundreds of flies each day, allowing them to make comparisons at different stages of development, between the sexes, and in flies that have genetic mutations. Thus, TRACT could be used to determine how different diseases perturb the connections within brain circuits. Additionally, because neural synapses change over time, TRACT allows the monitoring of synapse formation and destruction from day to day. Being able to see how and when neurons form or break synapses will be critical to understanding how the circuits in the brain assemble as the animal grows, and how they fall apart with age or disease.TRACT can be localized to focus in on the wiring of any particular neural circuit of interest, such as those that control movement, hunger, or vision. Lois and his group tested their method by examining neurons within the well-understood olfactory circuit, the neurons responsible for the sense of smell. Their results confirmed existing data regarding this particular circuit's wiring diagram. In addition, they examined the circadian circuit, which is responsible for the waking and sleeping cycle, where they detected new possible synaptic connections.TRACT, however, can do more than produce wiring diagrams. The transgenic flies can be genetically engineered so that the technique prompts receiving neurons to produce proteins that have a function, rather than colorful proteins that simply trace connections."We could use functional proteins to ask, 'What happens in the fly if I silence all the neurons that receive input from this one neuron?'" says Lois. "Or, conversely, 'What happens if I make the neurons that are connected to this neuron hyperactive?' Our technique not only allows us to create a wiring diagram of the brain, but also to genetically modify the function of neurons in a brain circuit."Previous methods for examining neural connections were time consuming and labor intensive, involving thousands of thin slices of a brain reconstructed into a three-dimensional structure. A laboratory using these techniques could only yield a diagram for a single, small piece of fruit-fly brain per year. Additionally, these approaches could not be performed on living animals, making it impossible to see how neurons communicated in real time.Because the TRACT method is completely genetically encoded, it is ideal for use in laboratory animals such as Drosophila and zebrafish; ultimately, Lois hopes to implement the technique in mice to enable the neural tracing of a mammalian brain. "TRACT is a new tool that will allow us to create wiring diagrams of brains and determine the function of connected neurons," he says. "This information will provide important clues towards understanding the complex workings of the human brain and its diseases."
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January 10, 2018
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https://www.sciencedaily.com/releases/2018/01/180110131501.htm
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With these special bacteria, a broccoli a day can keep the cancer doctor away
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Colorectal cancer is one of the most common cancers in the world, especially the developed world. Although the 5-year survival rates for earlier stages of this cancer are relatively good, at later stages survival goes down and the risk of cancer recurrence goes up considerably.
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To help address this problem, a team of researchers in the NUS Medicine lab of Associate Professor Matthew Chang have found a way to turn a humble cocktail of bacteria and vegetables into a targeted system that seeks out and kills colorectal cancer cells. The study, which was led by Dr Chun-Loong Ho, will be published online today and in the current issue of At the heart of this cancer-targeting system is an engineered form of True enough, the mixture of engineered probiotics with a broccoli extract or water containing the dietary substance killed more than 95% of colorectal cancer cells in a dish. Moreover, the mixture had no effect on cells from other types of cancer such as breast and stomach cancer. Strikingly, the probiotics-veggie combination reduced tumour numbers by 75% in mice with colorectal cancer. Also, the tumours that were detected in these mice were 3 times smaller than those in control mice which were not fed with the mixture.Dr Ho and Associate Professor Chang, along with colorectal cancer specialist Dr Yong Wei Peng at the National University Hospital, envision that these probiotics could be used in two ways: 1) as prevention, and 2) to clean up the cancer cells remaining after surgical removal of tumours. One day, colorectal cancer patients may be able to take the probiotics as a dietary supplement along with their broccoli to prevent colorectal cancer or to reduce recurrence after cancer surgery.As Associate Professor Chang puts it, "One exciting aspect of our strategy is that it just capitalizes on our lifestyle, potentially transforming our normal diet into a sustainable, low-cost therapeutic regimen. We hope that our strategy can be a useful complement to current cancer therapies."Or, even more simply, in Dr Ho's words, "Mothers are right after all, eating vegetables is important."
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January 9, 2018
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https://www.sciencedaily.com/releases/2018/01/180109161544.htm
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Promise of new antibiotics lies with shackling tiny toxic tetherballs to bacteria
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Biologists at The University of Texas at Austin have developed a method for rapidly screening hundreds of thousands of potential drugs for fighting infections, an innovation that holds promise for combating the growing scourge of antibiotic-resistant bacteria. The method involves engineering bacteria to produce and test molecules that are potentially toxic to themselves.
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A description of the method appears in the Jan. 25 print edition of the journal No new class of antibiotic has been discovered in 40 years -- many of the most accessible ones in nature already have been found, and the process for creating and testing new ones from scratch is slow and laborious -- but modern medicine is in sore need of them. According to the World Health Organization, antibiotics have added about 20 years to the average human lifespan. But their protective benefits are slipping away as bacteria evolve antibiotic resistance.In their proof of concept, the UT Austin team, led by Bryan Davies, screened about 800,000 molecules called peptides to see whether they had antimicrobial effects, meaning they killed harmful bacteria. Of those, several thousand killed E. coli bacteria, making them potential leads for antibiotics. Some antibiotics currently in use are peptides. Follow-up research will be necessary to determine which, if any, of the thousands of new leads are truly effective and safe in humans, but the researchers demonstrated that at least one such molecule, dubbed P7, also kills other forms of pathogenic bacteria and is safe in mice.With this method, called SLAY (Surface Localized Antimicrobial Display), one person can screen hundreds of thousands of similar peptides faster and more cost-effectively than existing methods can. Davies would like to see the method become a standard tool in the global hunt for new antibiotics."So what if we have a thousand groups all using this system to follow their own interests and their own peptides?" said Davies, assistant professor of molecular biosciences. "Once you enable a community of that size, then I think you have a better chance of actually finding a new antibiotic that works."A key advance in this work was figuring out how to get bacteria to produce molecules that might be toxic to themselves and to control how those molecules interact with their host bacteria."We thought, wouldn't it be great if a bacteria could synthesize the compound for us, because bacteria are cheap and easy to grow, and then test the compound on itself and report back and tell us, was that an antimicrobial or not?" Davies said.Their solution was to genetically engineer the bacteria to produce a molecule on the cell surface that is part peptide and part tether -- like a playground tetherball and its tether -- with one end fixed to the cell membrane and the other end free to float around. This allows the peptide to move around and make contact with the bacterial cell surface, as if it were free-floating like a drug in your bloodstream, but without interacting with other nearby bacteria.By ensuring that each version of the tetherball only interacts with the bacteria that produced it, the researchers could then make a big leap in efficiency. They could create hundreds of thousands of strains of bacteria -- each genetically engineered to produce a slightly different version of the tetherball -- and put all of these strains into the same test tube to grow. By running hundreds of thousands of experiments simultaneously, their method saves a tremendous amount of space, time and cost.Part of this process relies on a technique developed by UT Austin's George Georgiou in the 1990s that induces bacteria to produce proteins or peptides on their surfaces.To find out which tetherballs (peptides) knock out their hosts, the scientists use gene sequencing to identify which versions are being produced by bacteria at the start and which are being produced at the end.Following on the discovery that P7 kills pathogens, the team now plans to create thousands of subtle variations of this molecule, called derivatives, and run them through the same screening process to search for an even more effective version.Postdoctoral fellow Ashley Tucker led the experimental work to demonstrate use of the platform.Davies, Tucker and UT Austin have filed patent applications for the SLAY method and for the specific genetic sequences for the thousands of antimicrobial peptides they have discovered so far.In addition to Tucker and Davies, the paper's co-authors are Sean Leonard, Cory DuBois, Gregory Knauf, Ashley Cunningham, Claus Wilke and Stephen Trent, all of The University of Texas at Austin.This work was supported by the National Institutes of Health, Sanofi, the Welch Foundation, the Defense Advanced Research Projects Agency and the U.S. Army Research Office.
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January 8, 2018
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https://www.sciencedaily.com/releases/2018/01/180108093714.htm
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Yeast may be the solution to toxic waste clean-up
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About 46,000 nuclear weapons were produced during the Cold War era, leading to tremendous volumes of acidic radioactive liquid waste seeping into the environment. A new study suggests yeast as a potentially safer and more cost effective way to help clean up these radioactive waste sites. The study, "Prospects for Fungal Bioremediation of Acidic Radioactive Waste Sites: Characterization and Genome Sequence of
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The team of scientists at the Uniformed Services University of the Health Sciences (USU) found that one red-pigmented yeast, The team examined 27 yeasts isolated from diverse environments, testing to see how each was suitable for bioremediation under highly radioactive and acidic conditions. The yeast "Dr. Daly previously published a number of papers on potential use of genetically engineered
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January 8, 2018
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https://www.sciencedaily.com/releases/2018/01/180108090255.htm
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Less chewing the cud, more greening the fuel
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Plant biomass contains considerable calorific value but most of it makes up robust cell walls, an unappetising evolutionary advantage that helped grasses to survive foragers and prosper for more than 60 million years.
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The trouble is that this robustness still makes them less digestible in the rumen of cows and sheep and difficult to process in bioenergy refineries for ethanol fuel.But now a multinational team of researchers, from the UK, Brazil and the US, has pinpointed a gene involved in the stiffening of cell walls whose suppression increased the release of sugars by up to 60%. Their findings are reported today in "The impact is potentially global as every country uses grass crops to feed animals and several biofuel plants around the world use this feedstock," says Rowan Mitchell, a plant biologist at Rothamsted Research and the team's co-leader."In Brazil alone, the potential markets for this technology were valued last year at R$1300M ($400M) for biofuels and R$61M for forage cattle," says Hugo Molinari, Principal Investigator of the Laboratory of Genetics and Biotechnology at Embrapa Agroenergy, part of the Brazilian Agricultural Research Corporation (Embrapa) and the team's other co-leader.Billions of tonnes of biomass from grass crops are produced every year, notes Mitchell, and a key trait is its digestibility, which determines how economic it is to produce biofuels and how nutritious it is for animals. Increased cell wall stiffening, or feruloylation, reduces digestibility."We identified grass-specific genes as candidates for controlling cell wall feruloylation 10 years ago, but it has proved very difficult to demonstrate this role although many labs have tried," says Mitchell. "We now provide the first strong evidence for one of these genes."In the team's genetically modified plants, a transgene suppresses the endogenous gene responsible for feruloylation to around 20% of its normal activity. In this way, the biomass produced is less feruloylated than it would otherwise be in an unmodified plant."The suppression has no obvious effect on the plant's biomass production or on the appearance of the transgenic plants with lower feruloylation," notes Mitchell. "Scientifically, we now want to find out how the gene mediates feruloylation. In that way, we can see if we can make the process even more efficient."The findings are undoubtedly a boon in Brazil, where a burgeoning bioenergy industry produces ethanol from the non-food leftovers of other grass crops, such as maize stover and sugarcane residues, and from sugar cane grown as a dedicated energy crop. Increased efficiency of bioethanol production will help it to replace fossil fuel and reduce greenhouse gas emissions."Economically and environmentally, our livestock industry will benefit from more efficient foraging and our biofuels industry will benefit from biomass that needs fewer artificial enzymes to break it down during the hydrolysis process," notes Molinari.For John Ralph, co-author and field pioneer, the discovery has been hard won and is long overdue. "Various research groups 'had the feruloylation protein/gene imminently', and that was some 20 years ago," notes the Professor of Biochemistry at the University of Wisconsin-Madison and at the US Department of Energy's Great Lakes Bioenergy Research Center."Our group has been interested, since the early 1990s, in ferulate cross-linking in plant cell walls and developed the NMR methods that were useful in the characterisation here," notes Ralph. "This has been a tough one to discover."
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Genetically Modified
| 2,018 |
December 12, 2017
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https://www.sciencedaily.com/releases/2017/12/171212184119.htm
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Mosquito sex protein could provide key to controlling disease
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If you thought the sex lives of humans were complicated, consider the case of the female
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Understanding her sexual behavior could help prevent her from transmitting the deadly diseases she carries to millions of people every year. Yet many of the mechanisms governing her mating habits remain a mystery.Recently, however, researchers in the lab of Leslie B. Vosshall, Rockefeller's Robin Chemers Neustein Professor, demonstrated that a chemical transferred from the male of the species during sex plays a key role in shaping the female's sexual proclivities. Their work, which was led by postdoctoral associate Laura Duvall and appears in Duvall did not set out to reveal the secrets of the mosquito boudoir. Instead, she wanted to learn more about the biology behind female mosquitoes' host-seeking behaviors. In particular, she was curious about the role played by a small protein called HP-I. Previous studies had shown that this molecule is produced primarily by male The team disproved findings from other studies, however, which had suggested that HP-I suppresses the female's urge to seek out human hosts. The researchers paired males and females, including both mutant mosquitoes that were genetically modified to produce virtually no HP-I, and normal (or "wild-type") ones. After letting their subjects mate with one another in various combinations, the team looked for changes in the females' host-seeking behavior. But no matter with whom they had mated, the females remained just as keen on finding people to bite.Their attraction to male mosquitoes, however, was a different story.Scientists have long known that female To test that hypothesis, the team once again exposed females to males that produced HP-I, and males that didn't. But this time, they added a third group of suitors: males that produced HP-I, but were genetically modified so that their offspring would glow bright blue when viewed through a fluorescent microscope.By presenting the females with different combinations of fluorescent and non-fluorescent males (i.e., fluorescent males together with non-fluorescent males that produced HP-I, versus fluorescent males together with non-fluorescent males that lacked HP-I), the researchers were able to determine when the females were willing to accept only one mate -- and when they were willing to play the field."Whenever you see mixed fluorescent and non-fluorescent larvae, you know the female received sperm from more than one male," Duvall explains.The results of this mosquito paternity test were definitive: females that got a dose of HP-I during sex and then were offered another mate within an hour remained loyal to their initial partners, while females that got no HP-I did not. (Nevertheless, after 24 hours even females that mated with males lacking HP-I rejected additional partners, suggesting that other chemicals transmitted by the male are responsible for influencing female behavior over the long term.)Subsequent experiments showed that simply injecting HP-I directly into females was enough to trick the insects into thinking they had already mated, leading them to reject genuine warm-blooded males.In a final series of experiments, Duvall and her colleagues ventured into the exciting realm of inter-species sex.In the southern United States, Duvall and her team discovered that HP-I may help explain this curious reproductive pattern, as well: while the As a result, scientists now have a much better understanding of what shapes female mating behavior not only within one dangerous mosquito species, but across two of them. And those insights could have far-reaching implications.For example, scientists might eventually be able to limit the number of disease-carrying mosquitoes by using a substance like HP-I to persuade females to avoid mating in the first place. And while vector-control specialists are already attempting to wipe out mosquito populations by introducing genetically modified sterile males into the field, that strategy will only work if the females they encounter remain loyal to their sterile mates -- behavior that potentially could be elicited with a mosquito love potion informed by Duvall's research.
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Genetically Modified
| 2,017 |
December 7, 2017
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https://www.sciencedaily.com/releases/2017/12/171207141735.htm
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CRISPR-Cas9 technique targeting epigenetics reverses disease in mice
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Much of the enthusiasm around gene-editing techniques, particularly the CRISPR-Cas9 technology, centers on the ability to insert or remove genes or to repair disease-causing mutations. A major concern of the CRISPR-Cas9 approach, in which the double-stranded DNA molecule is cut, is how the cell responds to that cut and how it is repaired. With some frequency, this technique leaves new mutations in its wake with uncertain side effects.
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In a paper appearing in the journal "Cutting DNA opens the door to introducing new mutations," says senior author Juan Carlos Izpisua Belmonte of the Salk Institute for Biological Studies whose laboratory developed the new technique. "That is something that is going to stay with us with CRISPR or any other tool we develop that cuts DNA. It is a major bottleneck in the field of genetics -- the possibility that the cell, after the DNA is cut, may introduce harmful mistakes."That fact guided every experiment in the Belmonte lab as they developed the technique using a modified CRISPR-Cas9 system that does not cut the DNA. Their findings are the first to provide evidence that one can alter the phenotype of an animal with a epigenetic editing technology, preserving DNA integrity.The principal idea behind the Salk technique is the use of two adeno-associated viruses (AAVs) as the machinery to introduce their genetic manipulation machinery to cells in post-natal mice. The researchers inserted the gene for the Cas9 enzyme into one AAV virus. They used another AAV virus to introduce a short single guide RNA (sgRNA), which specifies the precise location in the mouse genome where Cas9 will bind, and a transcriptional activator. The shorter sgRNA is only 14 or 15 nucleotides compared with the standard 20 nucleotides used in most CRISPR-Cas9 techniques, and this prevents Cas9 from cutting the DNA."Basically, we used the modified guide RNA to bring a transcriptional activator to work together with the Cas9 and delivered that complex to the region of the genome we were interested in," says co-first author Hsin-Kai Liao of the Belmonte laboratory.The complex sits in the region of DNA of interest and promotes expression of a gene of interest. Similar techniques could be used to activate virtually any gene or genetic pathway without the risk of introducing potentially harmful mutations."We wanted to change the cell fate with therapeutic efficiency without a DNA cut," co-first author Fumiyuki Hatanaka explains.Strikingly, the team demonstrated disease reversal in several disease models in mice. In a mouse model of acute kidney disease, they showed that the technique activated previously damaged or silenced genes to restore normal kidney function. They were also able to induce some liver cells to differentiate into pancreatic ?-like cells, which produce insulin, to partially rescue a mouse model of type 1 diabetes.The team also showed that they could recover muscle growth and function in mouse models of muscular dystrophy, a disease with a known gene mutation. Instead of trying to correct the mutated gene, the researchers increased the expression of genes in the same pathway as the mutated gene, over-riding the effect of the damaged gene. "We are not fixing the gene; the mutation is still there," says Belmonte, "Instead, we are working on the epigenome and the mice recover the expression of other genes in the same pathway. That is enough to recover the muscle function of these mutant mice."Preliminary data suggest that the technique is safe and does not produce unwanted genetic mutations. However, the researchers are pursuing further studies to ensure safety, practicality, and efficiency before considering bringing it to a clinical environment.Belmonte sees this technology as a way of potentially treating neurological disorders such as Alzheimer's and Parkinson's diseases. Just as the technique restored kidney, muscle, and insulin-producing function in the mouse models, he sees a future for rejuvenating neuronal populations, maybe even one day in human patients.
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Genetically Modified
| 2,017 |
December 5, 2017
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https://www.sciencedaily.com/releases/2017/12/171205130112.htm
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Engineers 3-D print a 'living tattoo'
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MIT engineers have devised a 3-D printing technique that uses a new kind of ink made from genetically programmed living cells.
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The cells are engineered to light up in response to a variety of stimuli. When mixed with a slurry of hydrogel and nutrients, the cells can be printed, layer by layer, to form three-dimensional, interactive structures and devices.The team has then demonstrated its technique by printing a "living tattoo" -- a thin, transparent patch patterned with live bacteria cells in the shape of a tree. Each branch of the tree is lined with cells sensitive to a different chemical or molecular compound. When the patch is adhered to skin that has been exposed to the same compounds, corresponding regions of the tree light up in response.The researchers, led by Xuanhe Zhao, the Noyce Career Development Professor in MIT's Department of Mechanical Engineering, and Timothy Lu, associate professor of biological engineering and of electrical engineering and computer science, say that their technique can be used to fabricate "active" materials for wearable sensors and interactive displays. Such materials can be patterned with live cells engineered to sense environmental chemicals and pollutants as well as changes in pH and temperature.What's more, the team developed a model to predict the interactions between cells within a given 3-D-printed structure, under a variety of conditions. The team says researchers can use the model as a guide in designing responsive living materials.Zhao, Lu, and their colleagues have published their results today in the journal In recent years, scientists have explored a variety of responsive materials as the basis for 3D-printed inks. For instance, scientists have used inks made from temperature-sensitive polymers to print heat-responsive shape-shifting objects. Others have printed photoactivated structures from polymers that shrink and stretch in response to light.Zhao's team, working with bioengineers in Lu's lab, realized that live cells might also serve as responsive materials for 3D-printed inks, particularly as they can be genetically engineered to respond to a variety of stimuli. The researchers are not the first to consider 3-D printing genetically engineered cells; others have attempted to do so using live mammalian cells, but with little success."It turns out those cells were dying during the printing process, because mammalian cells are basically lipid bilayer balloons," Yuk says. "They are too weak, and they easily rupture."Instead, the team identified a hardier cell type in bacteria. Bacterial cells have tough cell walls that are able to survive relatively harsh conditions, such as the forces applied to ink as it is pushed through a printer's nozzle. Furthermore, bacteria, unlike mammalian cells, are compatible with most hydrogels -- gel-like materials that are made from a mix of mostly water and a bit of polymer. The group found that hydrogels can provide an aqueous environment that can support living bacteria.The researchers carried out a screening test to identify the type of hydrogel that would best host bacterial cells. After an extensive search, a hydrogel with pluronic acid was found to be the most compatible material. The hydrogel also exhibited an ideal consistency for 3-D printing."This hydrogel has ideal flow characteristics for printing through a nozzle," Zhao says. "It's like squeezing out toothpaste. You need [the ink] to flow out of a nozzle like toothpaste, and it can maintain its shape after it's printed."Lu provided the team with bacterial cells engineered to light up in response to a variety of chemical stimuli. The researchers then came up with a recipe for their 3-D ink, using a combination of bacteria, hydrogel, and nutrients to sustain the cells and maintain their functionality."We found this new ink formula works very well and can print at a high resolution of about 30 micrometers per feature," Zhao says. "That means each line we print contains only a few cells. We can also print relatively large-scale structures, measuring several centimeters."They printed the ink using a custom 3-D printer that they built using standard elements combined with fixtures they machined themselves. To demonstrate the technique, the team printed a pattern of hydrogel with cells in the shape of a tree on an elastomer layer. After printing, they solidified, or cured, the patch by exposing it to ultraviolet radiation. They then adhere the transparent elastomer layer with the living patterns on it, to skin.To test the patch, the researchers smeared several chemical compounds onto the back of a test subject's hand, then pressed the hydrogel patch over the exposed skin. Over several hours, branches of the patch's tree lit up when bacteria sensed their corresponding chemical stimuli.The researchers also engineered bacteria to communicate with each other; for instance they programmed some cells to light up only when they receive a certain signal from another cell. To test this type of communication in a 3-D structure, they printed a thin sheet of hydrogel filaments with "input," or signal-producing bacteria and chemicals, overlaid with another layer of filaments of an "output," or signal-receiving bacteria. They found the output filaments lit up only when they overlapped and received input signals from corresponding bacteria .Yuk says in the future, researchers may use the team's technique to print "living computers" -- structures with multiple types of cells that communicate with each other, passing signals back and forth, much like transistors on a microchip."This is very future work, but we expect to be able to print living computational platforms that could be wearable," Yuk says.For more near-term applications, the researchers are aiming to fabricate customized sensors, in the form of flexible patches and stickers that could be engineered to detect a variety of chemical and molecular compounds. They also envision their technique may be used to manufacture drug capsules and surgical implants, containing cells engineered produce compounds such as glucose, to be released therapeutically over time."We can use bacterial cells like workers in a 3-D factory," Liu says. "They can be engineered to produce drugs within a 3-D scaffold, and applications should not be confined to epidermal devices. As long as the fabrication method and approach are viable, applications such as implants and ingestibles should be possible."Video:
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Genetically Modified
| 2,017 |
December 5, 2017
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https://www.sciencedaily.com/releases/2017/12/171205091552.htm
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Girls will be boys: Sex reversal in dragon lizards
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One of Australia's iconic lizard species is hiding a secret -- female central bearded dragon embryos temporarily grow the lizard equivalent of a penis during development.
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Researchers at The University of Queensland, the University of Canberra and CSIRO made the discovery while investigating what happens to the body and genitalia of male dragons that reverse their sex at high temperature treatment.UQ School of Biological Sciences researcher Dr Vera Weisbecker said while the researchers expected to see some differences in the development of the male dragons' genitalia, it was their female counterparts who caused a stir."The study has provided the first detailed developmental timeline in dragon embryos of genetically female and sex-reversed (genetically male) female dragons at normal and high temperatures," Dr Weisbecker said."Our team incubated 265 bearded dragon eggs at two temperatures -- either at 28 or 36 degrees Celsius, the latter of which causes genetically male dragons to reverse their sex."The way these females grew hemipenes, the equivalent of a mammalian penis, was decidedly weird."Dr Weisbecker's Honours student Sarah Whiteley said the results of the study were big surprise."I noticed that female embryos first grew a pair of hemipenes, just like male embryos, and only lost them closer to hatching," said Ms Whiteley."Either temperature-dependent sex determination, or sex chromosomes, usually determined the development of genitalia in snakes and lizards."While sex determination is a major switch in individual development, we know little about the differences between the two developmental modes."Understanding these might give us some insights into the evolution of our own, genetically determined sexes."Dr Weisbecker said the findings served as a timely reminder of how little science understood about the evolution of genitalia in vertebrates, including humans."One of the biggest barriers for broader understanding is that there is scant knowledge on the female genitalia of reptiles, compared to a relatively large body of literature on male genital development and diversity," she said.Dr Weisbecker said the study highlighted the resilience of the body and genitalia of central bearded dragons to extreme incubation temperatures."Hot temperatures produce nearly all-female clutches so that increasing temperatures during climate change still represent a potential threat to the species," she said.
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Genetically Modified
| 2,017 |
December 4, 2017
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https://www.sciencedaily.com/releases/2017/12/171204094958.htm
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Refrigeration technology to maintain cold-stored mouse sperm viability for 10 days
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A Japanese research team from Kumamoto University has succeeded in developing a refrigeration preservation technology that maintains the fertilization functionality of mouse sperm for 10 days. Previously, the maximum freezing period was limited to three days, but by extending the preservation period by over three times that amount, it is now possible to send sperm of genetically modified mice to research organizations around the world.
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Many universities and pharmaceutical companies are engaged in research and development using genetically modified mice that have certain genes manipulated to reproduce human diseases. Since these mice are useful for tasks such as ascertaining the safety of drugs or investigating the cause of a disease, they are frequently transported to laboratories around the world. It is common to transport live mice in special containers but there is a risk that they might die due to stress during shipping, or escape due to mishandling or an accident. This is highly undesirable from the viewpoints of animal welfare and ecosystem preservation.Previously, the Institute of Resource Development and Analysis at Kumamoto University developed a reproductive engineering technology to efficiently produce, store, and supply genetically modified mice; a technology that is now used in research institutions around the world. The research group has also been conducting research on refrigerated sperm transportation as a method to replace the transportation of adult genetically modified mice. By performing in vitro fertilization with refrigerated sperm, it is possible to prepare a large number of genetically modified mice all at once. In other words, refrigerating and transporting the sperm of genetically modified mice solves all the problems live animal transportation.Using the refrigerated transportation method, the researchers conducted mutual transportation tests between Kumamoto University in the south of Japan and Asahikawa Medical University in the north, and between Kumamoto University and the University of California Davis. However, the period during which the mouse sperm could be refrigerated and remain viable was limited to three days. After that time the fertilizing ability of the sperm decreased. When attempting to transport genetically modified mice around the world, extension of the safe refrigeration period was necessary.The researchers aimed to improve the low temperature tolerance of sperm by adding quercetin, which is an antioxidant contained in cold-hardy plants, and dimethylsulfoxide (DMSO), which is widely used as a cryoprotective substance, to a preservation solution. The two substances dramatically improved cold-preserved sperm motility and allowed its fertilizing ability to be maintained for 10 days. Using the refrigerated sperm, the researchers were able to fertilize an egg in vitro and produce a normal mouse pup. In addition, they investigated the function of sperm treated with quercetin and DMSO in detail and found that the activity of the energy-producing mitochondria was elevated. Observation of the sperm with a fluorescence microscope revealed that quercetin accumulated in the middle of the sperm where mitochondria are present. The results suggest that quercetin may protect the mitochondria in sperm."This research makes it possible to transport genetically modified mice safely and easily to research organizations around the world," said study leader, Dr. Toru Takeo of Kumamoto University. "It is expected that this accelerates international collaborative research and contributes to the development of medicine · life science research."This research result was posted online in the journal
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Genetically Modified
| 2,017 |
November 30, 2017
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https://www.sciencedaily.com/releases/2017/11/171130122856.htm
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Interrupted reprogramming converts adult cells into high yields of progenitor-like cells
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A modified version of iPS methodology, called interrupted reprogramming, allows for a highly controlled, potentially safer, and more cost-effective strategy for generating progenitor-like cells from adult cells. As demonstrated November 30 in the journal
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"A major block in the critical path of regenerative medicine is the lack of suitable cells to restore function or repair damage," says co-senior author Tom Waddell, a thoracic surgeon at the University of Toronto. "Our approach starts with purifying the cell type we want and then manipulating it to give those cell types characteristics of progenitor cells, which can grow rapidly but produce only a few cell types. As such, it is much more direct, more rapid, and the batches of cells are more purified."In recent years, induced pluripotent stem (iPS) cells have generated a great deal of interest as a potentially unlimited source of various cell types for transplantation. This method involves genetically reprogramming skin cells taken from adult donors to an embryonic stem-cell-like state, growing these immature cells to large numbers, and then converting them into specialized cell types found in different parts of the body. A major advantage of this approach is the ability to generate patient-specific iPS cells for transplantation, thereby minimizing the risk of harmful immune reactions.Despite significant progress, these protocols remain limited by low yield and purity of the desired mature cell types, as well as the potential of immature cells to form tumors. Moreover, there is no standardized approach applicable to all cell types, and the development of personalized therapies based on patient-derived pluripotent cells remains very expensive and time consuming. "We have pursued cell therapy for lung diseases for many years," Waddell says. "One key issue is how to get the right type of cells and lots of them. To avoid rejection, we need to use cells from the actual patient."To address these issues, Waddell and co-senior study author Andras Nagy of Mount Sinai Hospital developed an interrupted reprogramming strategy, which is a modified version of the iPS methodology. The researchers started to genetically reprogram adult Club cells isolated from mice, transiently expressing the four iPS reprogramming factors, but interrupted the process early, prior to reaching the pluripotent state, to generate progenitor-like cells, which are more committed to a specific lineage and show more controlled proliferation than pluripotent cells."The reprogramming process had previously been considered as an all-or-none process," Waddell says. "We were surprised to the extent that it can be fine-tuned by the timing and dosing of the drug used to activate the reprogramming factors. That is interesting as it gives lots of opportunities for control, but it does mean we have lots of work to do to get it right."The researchers showed that the resulting Club-iPL cells could give rise to not only Club cells, but also to other respiratory tract cells such as mucus-secreting goblet cells and ciliated epithelial cells that produce the CFTR protein, which is mutated in patients with cystic fibrosis. When the Club-iPL cells were administered to CFTR-deficient mice, the cells incorporated into tissue lining the respiratory tract and partially restored levels of CFTR in the lungs without inducing tumor formation. This technology can theoretically be applied to almost any cell type that can be isolated and purified, and isolation of highly purified populations of adult cells from most organs is already possible with existing techniques."To create specialized cell types for use in cell therapy requires only that we insert the genes (or use non-transgenic approaches) and then test the drug dose and timing required for each cell type and each patient, so it should be relatively scalable at low cost compared to other approaches using each patient's own cells," Waddell says. "It should be very easy for other labs to use a similar approach."According to the authors, the approach could be used for a variety of regenerative medicine practices, including cell replacement therapy, disease modelling, and drug screening for human diseases. But there is still a long way to go before clinical translation. For their own part, the researchers plan to test this approach with other cell types, including human cells. They will also try to determine if there are safe ways to engraft these cells in human lungs. "The study is a proof of principle, the way this concept may ultimately be used in humans could be different, and it will be many years before this will be attempted in humans," Waddell says.
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Genetically Modified
| 2,017 |
November 30, 2017
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https://www.sciencedaily.com/releases/2017/11/171130122845.htm
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Why are genetically identical individuals different? Ask your mum!
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Does the age of a mother influence the traits and characteristics of her progeny, and how? A team of scientists at the Centre for Genomic Regulation (CRG) in Barcelona have addressed these questions by studying tiny, genetically identical C. elegans worms. Their results have been published in
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"Our lab has long been interested in understanding why genetically identical individuals sharing the same environment still often differ substantially in their characteristics," explains Ben Lehner, ICREA Professor and Coordinator of the Systems Biology Program at CRG. "Through a rather circuitous route, we have now identified a major cause of these differences in one of the main model organisms that we study.""We observed that the age of a mother has a major impact on the physiology of her offspring" states Marcos Francisco Perez, PhD student and co-first author of this work. "Surprisingly we found that it is the youngest mothers that produce offspring that are impaired for many characteristics such as their size, growth rate, and starvation resistance," explains post-doctoral researcher and co-first author of the study, Mirko Francesconi. "The offspring of young mothers also have fewer offspring themselves when they become adults," he adds."These differences are caused in part because young mothers provide less of a specific protein complex to their embryos," adds Marcos Francisco Perez. Why would a worm produce low quality progeny early in life? "Producing progeny early in life, even if they are lower quality, has a major benefit because it dramatically shortens the generation time of the species," explains Marcos Francisco Perez."What's particularly interesting is that the age of an individual's mother determines their characteristics throughout their lives," adds Ben Lehner. "This is a really interesting example of how the physiology of a previous generation can alter not only the development of an animal but also its characteristics as a mature adult."Ben Lehner and his team are interested in understanding what makes individuals different and how these differences originate in the interactions between genetic, environmental, ancestral and stochastic sources of variation. Worms are a great species to use in this type of study, because scientists can raise large populations of genetically identical individuals in the same laboratory environment. Worms and humans are evolutionarily distant but still share a large fraction of their genes, as well as most of the major genetic pathways which regulate development, metabolism and nutrition. Still, their results concerning the effect of maternal age do not translate to humans but illustrate the kind of ways in which differences between genetically identical individuals might arise."Our results are also important for the thousands of people doing research in this species. People don't consider maternal age when designing experiments but now we have shown that it is an important factor," conclude the scientists.
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Genetically Modified
| 2,017 |
November 27, 2017
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https://www.sciencedaily.com/releases/2017/11/171127135832.htm
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Large-scale approach reveals imperfect actor in plant biotechnology
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A research team led by Whitehead Institute for Biomedical Research has harnessed metabolomic technologies to unravel the molecular activities of a key protein that can enable plants to withstand a common herbicide. Their findings reveal how the protein -- a kind of catalyst or enzyme, first isolated in bacteria and introduced into plants, including crops such as corn and soybeans, in the 1990's -- can sometimes act imprecisely, and how it can be successfully re-engineered to be more precise. The new study, which appears online in the journal
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"Our work underscores a critical aspect of bioengineering that we are now becoming technically able to address," says senior author Jing-Ke Weng, a Member of the Whitehead Institute and an assistant professor of biology at the Massachusetts Institute of Technology. "We know that enzymes can behave indiscriminately. Now, we have the scientific capabilities to detect their molecular side effects, and we can leverage those insights to design smarter enzymes with enhanced specificity."Plants provide an extraordinary model for scientists to study how metabolism changes over time. Because they cannot escape from predators or search for new food sources when supplies run low, plants must often grapple with an array of environmental insults using what is readily available -- their own internal biochemistry."Although they appear to be stationary, plants have rapidly evolving metabolic systems," Weng explains. "Now, we can gain an unprecedented view of these changes because of cutting-edge techniques like metabolomics, allowing us to analyze metabolites and other biochemicals on a broad scale."Key players in this evolutionary process -- and a major focus of research in Weng's laboratory -- are enzymes. Traditionally, these naturally occurring catalysts have been viewed as mini-machines, taking the proper starting material (or substrate) and flawlessly converting it to the correct product. But Weng and other scientists now recognize that they make mistakes -- often by latching on to an unintended substrate. "This concept, known as enzyme promiscuity, has a variety of implications, both in enzyme evolution and more broadly, in human disease," Weng says.It also has implications for bioengineering, as Bastien Christ, a postdoctoral fellow in Weng's laboratory, and his colleagues recently discovered.Christ, then a graduate student in Stefan Hörtensteiner's lab at the University of Zurich in Switzerland, was studying a particular strain of the flowering plant Arabidopsis thaliana as part of a separate project, and he made a puzzling observation: two biochemical compounds were found at unusually high levels in their leaves.Strangely, these compounds (called acetyl-aminoadipate and acetyl-tryptophan) weren't present in any of the normal, so-called "wildtype" plants. As he and his colleagues searched for an explanation, they narrowed in on the source: an enzyme, called BAR, that was engineered into the plants as a kind of chemical beacon, enabling scientists to more readily study them.But BAR is more than just a tool for scientists. It is also one of the most commonly deployed traits in genetically modified crops, such as soybeans, corn, and cotton, enabling them to withstand a widely-used herbicide (known as phosphinothricin or glufosinate).For decades, scientists have known that BAR, originally isolated from bacteria, can render the herbicide inactive by tacking on a short string of chemicals, made of two carbons and one oxygen (also called an acetyl group). As the researchers describe in their Nature Plants paper, is has a promiscuous side, and can work on other substrates, too, such as the amino acids tryptophan and aminoadipate (a lysine derivative).That explains why they can detect the unintended products (acetyl-tryptophan and acetyl-aminoadipate) in crops genetically engineered to carry BAR, such as soybeans and canola.Their research included detailed studies of the BAR protein, including crystal structures of the protein bound to its substrates. This provided them with a blueprint for how to strategically modify BAR to make it less promiscuous, and favor only the herbicide as a substrate and not the amino acids. Christ and his colleagues created several versions that lack the non-specific activity of the original BAR protein."These are natural catalysts, so when we borrow them from an organism and put them into another, they may not necessarily be perfect for our purposes," Christ says. "Gathering this kind of fundamental knowledge about how enzymes work and how their structure influences function can teach us how to select the best tools for bioengineering."There are other important lessons, too. When the BAR trait was first evaluated by the U.S. FDA -- in 1995, for use in canola, and in subsequent years for other crops -- metabolomics was largely non-existent as a technology for biomedical research. Therefore, it could not be applied toward the characterization of genetically engineered plants and foods, as part of their regulatory review. Nevertheless, acetyl-aminoadipate and acetyl-tryptophan, which are normally present in humans, have been reviewed by the FDA and are safe for human and animal consumption.Weng and his colleagues believe their study makes a strong case for considering metabolomics analyses as part of the review process for future genetically engineered crops. "This is a cautionary tale," Weng says.
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Genetically Modified
| 2,017 |
November 24, 2017
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https://www.sciencedaily.com/releases/2017/11/171124084333.htm
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World's smallest tape recorder is built from microbes
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Through a few clever molecular hacks, researchers at Columbia University Medical Center have converted a natural bacterial immune system into a microscopic data recorder, laying the groundwork for a new class of technologies that use bacterial cells for everything from disease diagnosis to environmental monitoring.
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The researchers modified an ordinary laboratory strain of the ubiquitous human gut microbe "Such bacteria, swallowed by a patient, might be able to record the changes they experience through the whole digestive tract, yielding an unprecedented view of previously inaccessible phenomena," says Harris Wang, assistant professor in the Department of Pathology and Cell Biology and Systems Biology at CUMC and senior author on the new work, described in today's issue of Wang and members of his laboratory created the microscopic data recorder by taking advantage of CRISPR-Cas, an immune system in many species of bacteria. CRISPR-Cas copies snippets of DNA from invading viruses so that subsequent generations of bacteria can repel these pathogens more effectively. As a result, the CRISPR locus of the bacterial genome accumulates a chronological record of the bacterial viruses that it and its ancestors have survived. When those same viruses try to infect again, the CRISPR-Cas system can recognize and eliminate them."The CRISPR-Cas system is a natural biological memory device," says Wang. "From an engineering perspective that's actually quite nice, because it's already a system that has been honed through evolution to be really great at storing information."CRISPR-Cas normally uses its recorded sequences to detect and cut the DNA of incoming phages. The specificity of this DNA cutting activity has made CRISPR-Cas the darling of gene therapy researchers, who have modified it to make precise changes in the genomes of cultured cells, laboratory animals, and even humans. Indeed, over a dozen clinical trials are now underway to treat various diseases through CRISPR-Cas gene therapy.But Ravi Sheth, a graduate student in Wang's laboratory, saw unrealized potential in CRISPR-Cas's recording function. "When you think about recording temporally changing signals with electronics, or an audio recording ... that's a very powerful technology, but we were thinking how can you scale this to living cells themselves?" says Sheth.To build their microscopic recorder, Sheth and other members of the Wang lab modified a piece of DNA called a plasmid, giving it the ability to create more copies of itself in the bacterial cell in response to an external signal. A separate recording plasmid, which drives the recorder and marks time, expresses components of the CRISPR-Cas system. In the absence of an external signal, only the recording plasmid is active, and the cell adds copies of a spacer sequence to the CRISPR locus in its genome. When an external signal is detected by the cell, the other plasmid is also activated, leading to insertion of its sequences instead. The result is a mixture of background sequences that record time and signal sequences that change depending on the cell's environment. The researchers can then examine the bacterial CRISPR locus and use computational tools to read the recording and its timing.The current paper proves the system can handle at least three simultaneous signals and record for days."Now we're planning to look at various markers that might be altered under changes in natural or disease states, in the gastrointestinal system or elsewhere," says Dr. Wang.Synthetic biologists have previously used CRISPR to store poems, books, and images in DNA, but this is the first time CRISPR has been used to record cellular activity and the timing of those events.
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Genetically Modified
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November 17, 2017
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https://www.sciencedaily.com/releases/2017/11/171117115446.htm
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Age, gut bacteria contribute to MS disease progression, according to study
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Researchers at Rutgers Robert Wood Johnson Medical School published a study suggesting that gut bacteria at young age can contribute to Multiple sclerosis (MS) disease onset and progression.
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In this study, published in the October 31 issue of the At first, when the genetically modified mice were put in a sterile, germ-free environment, they did not develop MS. When exposed to a normal environment that would normally contain bacteria, the mice did develop MS-like disease and inflammation in their bowels, suggesting gut bacteria is a risk factor that triggers MS disease development.The study showed a link between gut bacteria and MS-like disease incidence, which was more prominent at a younger age, when MS is also more prevalent. The younger mice were more prone to develop MS than the older mice. Together, age, gut bacteria, and MS-risk genes collaboratively seem to trigger disease. This study is also the first to identify mechanisms by which gut bacteria triggers changes in the immune system that underlie MS progression."The findings could have therapeutic implications on slowing down MS progression by manipulating gut bacteria," says Suhayl Dhib-Jalbut, Director of Rutgers-Robert Wood Johnson Center for Multiple Sclerosis. Future research could lead to the elimination of harmful types of gut bacteria that wereshown to cause MS progression, or conversely enhance beneficial bacteria that protects from disease progression. The investigators recently received NIH funding to examine their findings in MS patients.
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Genetically Modified
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November 16, 2017
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https://www.sciencedaily.com/releases/2017/11/171116105011.htm
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New procedures for DNA stability
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Researchers from the University of Seville at the Andalusian Centre for Molecular Biology and Regenerative Medicine (Centro Andaluz de Biología Molecular y Medicina Regenerativa -- Cabimer) have discovered that in eukaryotic cells the proximity of the genes to the nuclear pores, which are found in the nuclear membrane, contributes to maintaining the integrity of the genome. This is due to the fact that the anchoring of DNA to the pore during transcription avoids the formation of DNA-RNA hybrids, which are a natural source of DNA breaks and genome instability.
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The proximity and anchoring of the genes to the nuclear pores during transcription has been known of for more than a decade. It makes it possible for the nascent RNA to be carried out of the nucleus. "In this work, we have seen that if DNA is located in the interior of the nucleus and removed from the nuclear pore, the formation of DNA-RNA hybrids are more likely. That is to say, the anchoring of DNA to the pore contributes to preserving the integrity of the genome by avoiding the formation of these structures," explains the University of Seville professor and director of Cabimer, Andrés Aguilera.The work was carried out on a model eukaryotic organism, the yeast Saccharomyces. In this a genetic count was made of new genes involved in the prevention of DNA-RNA hybrids, which cause genetic instability. From one collection of mutations of protein coding genes, they identified the nuclear components Mlp1 and Mlp2 of the macrocomplex that form the nuclear pores, preserved in all the eukaryotes, including the human ones. The molecular analysis of the null mutations (totally non-functioning) of these genes allowed it to be observed that DNA-RNA hybrids accumulated (detected via a specific anti-hybrid antibody) and increased the genetic instability that they caused. However, when the DNA in these mutations was again returned to the nuclear pore by means of a genetically-engineered artificial anchoring system, the hybrids and the instability were suppressed."It was particularly relevant that this system of artificial anchoring was also tested in THO-complex mutations, which also see increased DNA-RNA hybrids and the associated genetic instability, and we successfully managed to prevent the formation of DNA-RNA hybrids and instability," Aguilera highlighted.The accumulation of RNA-DNA hybrids in the genome is a source of genome instability in all organisms and has been associated with neurodegenerative diseases and cancer. The results of the research open new possibilities for understanding the cellular mechanisms responsible for genome instability and for being able to explore new therapeutic approaches.
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Genetically Modified
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November 15, 2017
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https://www.sciencedaily.com/releases/2017/11/171115091806.htm
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Saving cavendish: Panama disease-resistant bananas
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QUT researchers have developed and grown modified Cavendish bananas resistant to the devastating soil-borne fungus Fusarium wilt tropical race 4 (TR4), also known as Panama disease.
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In a world-first GM field trial conducted in heavily TR4-infested soil, one Cavendish line transformed with a gene taken from a wild banana remained completely TR4 free, while three others showed robust resistance. The results have just been published in The field trial, which ran from 2012 to 2015, was led by Distinguished Professor James Dale, from QUT's Centre for Tropical Crops and Biocommodities. It was conducted on a commercial banana plantation outside Humpty Doo in the Northern Territory previously affected by TR4. The soil was also heavily reinfested with disease for the trial.Professor Dale said the outcome was a major step towards protecting the US$12 billion Cavendish global export business, which is under serious threat from virulent TR4."These results are very exciting because it means we have a solution that can be used for controlling this disease," he said."We have a Cavendish banana that is resistant to this fungus that could be deployed, after deregulation, for growing in soils that have been infested with TR4."TR4 can remain in the soil for more than 40 years and there is no effective chemical control for it. It is a huge problem. It has devastated Cavendish plantations in many parts of the world and it is spreading rapidly across Asia."It is a very significant threat to commercial banana production worldwide."The researchers have begun an expanded field trial on the same Northern Territory plantation, growing the four RGA2 lines that showed resistance in the last trial, as well as newly developed lines of modified Cavendish Grand Nain and Williams cultivars.They will have the capacity to grow up to 9000 plants and quantify crop yield over the five-year trial."The aim is to select the best Grand Nain line and the best Williams line to take through to commercial release," Professor Dale said. "While in Australia we primarily grow Williams, in other parts of the world Grand Nain is very popular."Professor Dale said the correlation demonstrated between the RGA2 gene activity and TR4 resistance opened up new research."We can't make the assertion that the RGA2 gene is the gene responsible for the resistance in the original wild diploid banana, because in the modified Cavendish we significantly increased the gene's expression -- the level of its activity -- over its activity in the wild banana," he said."But we've established a correlation, and we've found that the RGA2 gene occurs naturally in Cavendish -- it just isn't very active."We are aiming to find a way to switch that gene on in the Cavendish through gene editing. We've started that project. It is not easy, it's a complex process that is a way off, with four or five years of lab work."We're also looking at as many genes as possible in the wild banana and screening them to identify other resistance genes, not only for resistance to TR4 but to other diseases."Other key findings of the field trial:
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Genetically Modified
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November 13, 2017
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https://www.sciencedaily.com/releases/2017/11/171113111049.htm
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Researchers fold a protein within a protein
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A team from the NUS Yong Loo Lin School of Medicine (NUS Medicine) has invented a fundamentally new way of folding and protecting recombinant proteins. Sourced from the rapidly expanding field of synthetic biology, this protein-in-a-protein technology can improve functional protein yields by 100-fold and protect recombinant proteins from heat, harsh chemicals and proteolysis.
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The expression and stabilisation of recombinant proteins is the cornerstone of the biologics and pharmaceutical industries. The costs and complexity associated with manufacturing difficult-to-fold recombinant proteins at an industrial scale are a significant limiting factor to their use in clinical and industrial applications.The study led by Dr Chester Drum, Assistant Professor at the Departments of Medicine and Biochemistry, NUS Medicine was published in the journal The researchers developed this protein-within-a-protein technology with the help of Archeoglobus fulgidus, a hardy bacteria that is naturally found in hydrothermal vents. These hyper-thermophilic bacteria have evolved unique solutions for protein folding and stabilisation due to the extreme environments in which they live.In particular, the researchers made use of an iron-carrying, 24-subunit protein in A. fulgidus called ferritin, whose natural function is to store and carry iron in the blood. Ferritin from A. fulgidus has two unique properties: first, four tiny pores in its shell provide small molecules access into the cavity; second, unlike human ferritin which is stable at low salt concentrations, the engineered A. fulgidus ferritin dissociates at low salt concentrations, allowing the contents of the cavity to be released by a simple pH switch from 8.0 to 5.8. Once dissociated, the POI can be released enzymatically.To demonstrate the wide versatility of their technology, the researchers tested their exoshell technology by fusing one of the 24 ferritin subunits around three POIs with diverse properties -- green fluorescent protein, horseradish peroxidase (HRP) and Renilla luciferase.Not only did the exoshell help increase the yields of all three POIs, the researchers were also able to deliver cofactors heme and calcium, in addition to oxidising conditions, to ensure that complex POIs such as HRP protein could fold and function properly.Besides helping to fold the POIs correctly, the exoshells were also protective against a wide range of denaturants, including high concentration trypsin; organic solvents such as acetonitrile and methanol; and denaturants such as urea, guanidine hydrochloric acid, and heat."We hypothesise that the significant increase in functional protein yield may be due to the complementation between the negatively charged proteins and the positively charged exoshell internal surface. Our findings highlight the potential of using highly engineered nanometer-sized shells as a synthetic biology tool to dramatically affect the production and stability of recombinant proteins," said Dr Drum, who is also a consultant cardiologist at the National University Hospital and director of the Clinical Trial Innovation Lab at TLGM, A*STAR.Recruited to the National University of Singapore in 2011, he has since received funding from the Singapore MIT Alliance for Research and Technology, National Medical Research Council, Biomedical Research Council, A*STAR and NUS Medicine.
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Genetically Modified
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November 8, 2017
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https://www.sciencedaily.com/releases/2017/11/171108124217.htm
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How the skin becomes inflamed: Toxin-producing bacteria
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Publishing online this week in
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"Our skin is covered with bacteria as part of our normal skin microbiome and typically serves as a barrier that protects us from infection and inflammation. However, when that barrier is broken, the increased exposure to certain bacteria really causes problems," says Lloyd Miller, M.D., Ph.D., associate professor of dermatology at the Johns Hopkins University School of Medicine.The bacteria Staphylococcus aureus, or S. aureus, is an important human pathogen and the most common cause of skin infections in people. Miller says, "20 to 30 percent of the U.S. population have S. aureus living on their skin or in their nose, and over time, up to 85 percent of people come into contact with it. Eczema is an inflammatory skin disease that affects 20 percent of children and about 5 percent of adults. Ninety percent of patients with eczema have exceedingly high numbers of S. aureus bacteria on their inflamed skin.""We don't really know what causes atopic dermatitis and there aren't many good treatments for it," says Miller. So his team set out to learn more about how the condition arises in hopes that other treatments can be developed.It was previously shown by others that a rare disease called generalized pustular psoriasis (in which the skin erupts into pustules) was caused by a genetic mutation that resulted in unrestrained activity of a protein normally produced in our skin, called IL-36. This, says Miller, was a clue that IL-36 might have something to do with how bacteria on the skin surface induce inflammation. So they set out to test this idea in mice. They soaked a small gauze pad with S. aureus and applied it to the back skin of normal mice and those that had been genetically engineered to lack the receptor for IL-36 that triggers inflammatory responses. Miller's team found the normal mice developed scaly and inflamed skin, and the genetically engineered mice lacking IL-36 activity had almost no skin inflammation."We are very excited about these results as there is currently only a single biologic treatment targeting an inflammatory mechanism in atopic dermatitis on the market. As there are patients who don't respond or have treatment failures, it would be better if there were biologics on the market that target alternative mechanisms involved in skin inflammation," says Miller.Untreated eczema can lead to other allergic conditions, including asthma, food allergies, seasonal allergies and conjunctivitis. Blocking the skin inflammation in eczema has the potential to prevent these unwanted conditions.
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Genetically Modified
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November 3, 2017
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https://www.sciencedaily.com/releases/2017/11/171103085311.htm
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Elucidation of bone regeneration mechanism
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How osteoblasts are supplied during bone regeneration has been controversial among bone researchers. According to Atsushi Kawakami, an Associate Professor who specializes in tissue regeneration and led the study, scientists disagree on how these cells are made.
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The new study uses genetically engineered transgenic zebrafish to show that a population of progenitor cells marked by high expression of matrix metalloproteinase 9, an enzyme that catabolizes collagens, provides osteoblasts during regeneration. Kazunori Ando, a graduate student who conducted the experiments, calls these cells osteoblast progenitor cells (OPCs). Consistently, eliminating OPCs prior to tissue injury significantly impaired bone regeneration. Overall, the study shows that OPCs are essential for bone regeneration.The researchers further investigated the developmental origin of OPCs and found that OPCs are derived from embryonic somites and reserved in niches of bone-forming tissues in adult animal as the source of osteoblasts. Embryonic somites produce osteoblasts during vertebrate development, but its relationship to adult osteoblasts was not known. The study revealed that OPCs derived from the somites are the dormant cells for later production of osteoblasts in adult animal.In conclusion, the findings suggest that a lineage of bone-producing cell, which are specified in embryonic somites, are maintained throughout the animal lives as progenitor cells for bone regeneration and also for bone maintenance."We use animal models because they show us a number of essential cellular and molecular mechanisms behind our existence. Considering the higher bone regeneration potential in zebrafish, OPCs will be a potential target for enhancing bone regeneration in mammals" said Kawakami.
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Genetically Modified
| 2,017 |
October 31, 2017
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https://www.sciencedaily.com/releases/2017/10/171031101826.htm
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Genetic study uncovers evolutionary history of dingoes
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A major study of dingo DNA has revealed dingoes most likely migrated to Australia in two separate waves via a former land bridge with Papua New Guinea.
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The find has significant implications for conservation, with researchers recommending the two genetically distinct populations of dingoes -- in the south-east and north-west of the country -- be treated as different groups for management and conservation purposes."Care should be taken not to move dingoes between the different wild populations," says study first author and UNSW Sydney scientist Dr Kylie Cairns."And captive breeding programs should ensure the two dingo populations are maintained separately, with genetic testing used to identify ancestry."Further inter-breeding also needs to be urgently prevented between domestic dogs and the south-eastern population of dingoes, which is threatened by genetic dilution, habitat loss and lethal control measures such as baiting and the recently reintroduced wild dog bounty in Victoria."Effective containment or neutering of male dogs in rural areas may help achieve this reduction in inter-breeding," says Dr Cairns, of the School of Biological, Earth and Environmental Sciences."Additionally, baiting and culling practices break apart dingo packs, leading to increased incidence of hybridisation. Alternative livestock protection measures need to be explored, such as livestock guardians, predator deterrents and improved dingo-proof fencing," she says.The study, by scientists from UNSW and the University of California, is published in the journal The study is the first broad study of the evolutionary history of dingoes around Australia using both mitochondrial and Y-chromosome genetic markers.The researchers sampled 127 dingoes across Australia as well as five New Guinea Singing Dogs from a North American captive population. A dataset of Y chromosome and mitochondrial control region data from 173 male dogs, including 94 dingoes, was also used.Only genetically pure dingoes were included in the study.The north-western population is found in Western Australia, the Northern Territory, northern parts of South Australia, and central and northern Queensland.The south-eastern population is found in New South Wales, the Australian Capital Territory, Victoria and southern parts of Queensland (including Fraser Island).The researchers believe the two groups may have migrated separately from Papua New Guinea over the now-flooded land bridge as long as 8000 to 10,000 years ago.Particularly in south-eastern states, they recommend a broad survey of dingoes in national parks and state forests be carried out to focus conservation efforts in key areas, and also that state and federal legislation allowing fatal control measures be reviewed.
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Genetically Modified
| 2,017 |
October 23, 2017
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https://www.sciencedaily.com/releases/2017/10/171023102228.htm
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Consumers see ‘organic’ and ‘non-GM’ food labels as synonymous
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Consumers are confused between foods labeled as "organic" and "non-genetically modified," according to a new study led by a University of Florida professor. In fact, researchers found that some consumers view the two labels as synonymous.
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When Congress approved the National Bioengineered Food Disclosure Standard in June 2016, lawmakers allowed companies two years -- until June 2018 -- to label their genetically modified (GM) food by text, symbol or an electronic digital link such as a QR code. The QR code is a machine-readable optical label that displays information when scanned.Besides QR codes, companies can label GM foods by adding words like: "contains genetically modified ingredients" in plain text on the packages, said Brandon McFadden, a UF/IFAS assistant professor of food and resource economics, and lead author of the study.McFadden and Purdue University agricultural economics professor Jayson Lusk conducted their research to find the best ways to communicate whether a food has GM ingredients. This research has implications for which foods consumers will buy, McFadden said.To gauge consumers' willingness to pay for food labeled as GM vs. non-GM, researchers conducted a national survey of 1,132 respondents.Specifically, researchers wanted to know how much consumers were willing to spend on food labeled as "USDA Organic" vs. that labeled "Non-GMO Project Verified." Genetically modified material is not allowed in food labeled "USDA Organic," while "Non-GMO Project" means the food has no more than 0.9 percent GM characteristics, according to the study.Researchers measured respondents' willingness to pay for a box of 12 granola bars and a pound of apples. Granola bars represent a manufactured food commonly differentiated by its absence of GM material, while apples are a fresh fruit that requires companies to tell if they contain GM material, the study said.In this study, when consumers looked at packages of Granola bars labeled "non-GMO Project," they were willing to spend 35 cents more than for the boxes that had text that read, "contains genetically engineered ingredients." With the "USDA Organic" label, consumers were willing to pay 9 cents more.With apples, respondents were willing to pay 35 cents more for those labeled "non-GMO Project" and 40 cents more for those labeled "USDA Organic."Participants' responses led McFadden to conclude that consumers don't distinguish definitions of the two food labels."For example, it's possible that a product labeled, 'Non-GMO Project Verified' more clearly communicates the absence of GM ingredients than a product labeled 'USDA Organic,'" said McFadden.In addition to willingness to pay for GM- and non-GM foods, researchers wanted to know how QR codes impact choices for foods labeled as containing GM ingredients. They also wanted to know how much consumers were willing to pay for food labeled as GM if that information came from a Quick Response -- or QR -- code. Study results showed consumers are willing to pay more for genetically modified food if the information is provided by a QR code."This finding indicates that many of the study respondents did not scan the QR code," McFadden said.That's because if all respondents scanned the QR code, there would not be a significant difference in their willingness to pay, he said. Since there is a significant difference, one can assume that many respondents did not scan the QR code, McFadden said."However, it is important to remember that this study is really a snapshot, and it is possible that over time, consumers will become more familiar with QR codes and be more likely to scan them," he said.The new study is published in the journal
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Genetically Modified
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October 19, 2017
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https://www.sciencedaily.com/releases/2017/10/171019142724.htm
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Gut bacterium indirectly causes symptoms by altering fruit fly microbiome
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CagA, a protein produced by the bacterium
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Microbes living in the human gut normally help keep people healthy, but disruptions to this microbial community can promote disease. Infections with specific microbial species can disrupt the gut microbiome, but it is unclear how such disruption occurs and whether it promotes disease.In the new study, Jones and her colleagues used Drosophila fruit flies to test the effects of infection with To test their hypothesis, the researchers genetically engineered fruit flies to express the CagA protein in their intestines, without being infected by They found that CagA expression in the fruit fly gut caused excess growth of intestinal cells and promoted immune system responses that are associated with Indeed, further investigation revealed that CagA expression was associated with a disrupted gut microbiome in the flies. Exposure to the CagA-expressing flies caused the same microbiome disruptions in normal flies, which was sufficient to cause the same symptoms of excess cell growth and immune response seen in the genetically altered flies.Overall, these findings show that CagA can indirectly cause disease symptoms by altering the gut microbiome. This raises the possibility that the harmful effects of infection with "Our work demonstrates for the first time that a bacterial virulence factor like CagA can alter commensal microbial communities to cause disease," the author explain. "This work also reveals that commensal microbial communities may participate in the progression of
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Genetically Modified
| 2,017 |
October 19, 2017
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https://www.sciencedaily.com/releases/2017/10/171019100818.htm
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Scientists find where HIV 'hides' to evade detection by the immune system
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In a decades-long game of hide and seek, scientists from Sydney's Westmead Institute for Medical Research have confirmed for the very first time the specific immune memory T-cells where infectious HIV 'hides' in the human body to evade detection by the immune system.
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The team, led by Associate Professor Sarah Palmer from the University of Sydney, developed a pioneering full-length genetic sequencing assay for HIV. Using this test, the team found that genetically-intact HIV hides in specific subsets of CD4+ T-cells.Associate Professor Palmer said that this next-generation test showed that HIV hides in the body's immune memory T-cells, which is how it avoids detection from the immune system."Previously it was thought that HIV was hiding primarily in central memory T-cells, but our new HIV genetic sequencing test has revealed that the majority of replication-competent virus is actually hiding in effector memory T-cells."HIV is really very clever. Essentially, it is hiding in the exact same cells within the immune system that are meant to attack it," she said.Effector memory T-cells are the cells in the body that 'remember' previous infections and how to defeat them. These are the cells that provide life-long immunity to infections such as measles or chicken pox.Associate Professor Palmer explained that only a very small proportion -- approximately five per cent -- of HIV is genetically intact. However, it is this small proportion of virus that hides in the effector memory T-cells and stops the immune system from fully destroying the virus and eliminating it from the body."When HIV replicates it makes a lot of errors and releases a lot of defective virus."But this five per cent of genetically intact HIV is the key. This virus inserts its genome into the body's memory cells and sits there quietly avoiding detection by the immune system," Associate Professor Palmer explained."These infected cells go into a resting state and stop producing HIV, but these latent cells can wake up and start making infectious HIV."It is a ticking time bomb waiting to re-infect a patient."The other 95 per cent of defective virus does send the immune system into overdrive. We suspect that this 'junk' HIV can act as a decoy and draw attention away from the "real" virus hiding in the effector memory T-cells," she said.Despite groundbreaking advances in the treatment of HIV, it remains a chronic illness across the globe. Neither a cure nor a vaccine has been achieved."Current HIV drugs stop the virus from replicating, but there is still no way for us to 'cure' an individual with HIV. Patients need drugs or chemotherapy for the rest of their lives."This is a particular problem in the developing world where only 50 per cent of people have access to regular HIV therapies."If a person suddenly stops taking their HIV treatments, the virus hidden in effector memory T-cells would spring to life and start producing more HIV, and the virus will spread throughout the body within two weeks."Now that we've identified where the replication-competent virus is hiding, we can start work towards targeting these cells with new therapies aimed at fully eliminating HIV from the body," Associate Professor Palmer concluded.
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Genetically Modified
| 2,017 |
October 18, 2017
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https://www.sciencedaily.com/releases/2017/10/171018151820.htm
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Obesity: Engineered proteins lower body weight in mice, rats and primates
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Researchers have created engineered proteins that lowered body weight, bloodstream insulin, and cholesterol levels in obese mice, rats, and primates. Their results could pave the way for urgently needed alternatives to bariatric surgery for treating obesity in humans -- the rates of which have nearly tripled worldwide since 1975.
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Based on the observation that obese mice, rats, and humans all had elevated serum concentrations of a protein called GDF15 compared to lean controls, Yumei Xiong and colleagues set out to develop therapies derived from the molecule. In multiple mouse models of diet-induced and genetic obesity, delivery of the GDF15 gene reduced body weights, food intake, and serum insulin levels in the animals.Because GDF15 has a short plasma half-life and is difficult to produce in substantial quantities, the scientists generated two different fusion proteins that were more stable in the circulation and led to higher yields. Both fusion proteins effectively decreased body weights for obese mice and cynomolgus monkeys.Interestingly, Xiong et al. further showed that the GDF15 regimen altered food preferences in mice -- leading the animals to opt for lower calorie chow when offered a choice between standard food and an extra-rich condensed-milk diet (untreated mice gorged themselves on the high-calorie eats).The authors determined that GDF15 activated a population of nerve cells called AP neurons that make up a portion of the gut-brain axis, yet note that further studies to identify the protein's cellular receptor are needed as potential therapeutics make their way to the clinic.
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Genetically Modified
| 2,017 |
October 18, 2017
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https://www.sciencedaily.com/releases/2017/10/171018132906.htm
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Nature or nurture? Innate social behaviors in the mouse brain
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Adult male mice have a simple repertoire of innate, or instinctive, social behaviors: When encountering a female, a male mouse will try to mate with it, and when encountering another male, the mouse will attack. The animals do not have to be taught to perform these behaviors. This has led to the widespread presumption among neuroscientists that the brain circuits mediating these behaviors are "hardwired," meaning that they are genetically encoded pathways with little flexibility.
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But new research from Caltech neuroscientists shows that these behaviors and the neurons that represent them are not as fixed as previously believed.The work appears in a paper in the October 19 issue of the journal The team used mice that had been genetically engineered so that neurons in a specific part of the brain involved in aggression and sexual behavior -- the ventromedial hypothalamus (VMH) -- would glow green when activated. To visualize this activation, a needle-thin glass lens was inserted into the hypothalamus, and images of flashing neurons were recorded by a miniature, portable microscope attached to the mouse's head. This brain imaging technology was originally developed by Anderson's collaborator at Stanford University, Mark Schnitzer, and obtained through Inscopix.The Caltech team first set up "resident/intruder tests," in which they imaged the brain of a socially and sexually experienced "resident" mouse in its cage as a single intruder mouse -- either a male or a female -- was introduced. The researchers found that during its encounters with other mice, one of two distinct sets of neurons in the VMH were activated -- one set if the other mouse was a male, and another if it was a female. Though these neurons are spatially intermingled, there is very little overlap between them, like grains of salt and pepper interspersed on a plate.Just by looking at the activation of these two neural populations, the scientists could reliably determine whether an animal was interacting with a male or a female. These observations seemed to support the idea that these distinct representations of males versus females are hardwired and genetically fixed from birth.To test this idea more directly, the researchers examined the behaviors of naïve mice -- those that had been maintained in isolation since weaning, without any social or sexual experience. If the sex distinction was indeed hardwired, then the researchers should have seen the separate activation of the groups of neurons specific for recognizing males versus females, even during the first encounters between these naïve mice and other male or female intruder mice.Surprisingly, to the contrary, the neurons of these naïve mice initially were similarly activated when the mice were exposed to either male or to female mice. At the same time, these mice initially exhibited little fighting (with males) or mating (with females) behaviors. Only after repeated social experience -- contact with either male or female mice for two minutes, five times a day, for three days -- did the separate sets of neurons representing male versus female mice appear. This separation occurred just as the mice began to exhibit aggression toward males and mating with females.Further studies indicated that social experience with a female seemed to be the key requirement for the mice to develop separate, sex-specific populations of neurons, as well as aggressive behavior. As little as 30 minutes of social interaction with a female, the team found, was enough to make naïve mice aggressive towards males 24 hours later, as well as to cause the separation of male- versus female-specific representations in the mouse's brain. Naïve mice that were exposed only to males did not develop aggressive behaviors, nor did they show this separation."The mice do not have sex-specific neurons from birth," says co-first author Ryan Remedios, postdoctoral scholar in biology and biological engineering. "The separation forms as a consequence of social experience, specifically from social experience with a female.""This is an unexpected discovery," says co-first author Ann Kennedy, a Caltech postdoctoral scholar in biology and biological engineering. "This area of the brain, the ventromedial hypothalamus, is a primitive, ancient region. We used to think of it as the basement of the brain, more like a plumbing system than a computer. Our study shows that this region exhibits plasticity and computation.""This is basic neuroscience research," says Anderson. "We are studying the nature versus nurture problem: how much of the brain's wiring and the animal's behavior is determined by genetics versus experience. These results reveal that even the circuitry for supposedly innate behaviors is not as hardwired as previously thought. This finding raises a whole new set of questions about how exactly social interactions with female mice can cause a change in patterns of brain activity and promote aggressiveness.""The fact that there is a very close anatomical relationship between cells encoding sex and aggression is biologically very important because these primitive behaviors are essential for survival," Anderson adds. "It also raises the question of whether people that exhibit violent sexual behavior are somehow 'getting their neural wires crossed.' If this were true, then someday we might be able to treat someone who's a habitual violent sexual offender by functionally disentangling their neurons. But this is currently just an idea, and any therapies based on this research are a long way off."
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Genetically Modified
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October 18, 2017
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https://www.sciencedaily.com/releases/2017/10/171018113525.htm
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Turning brain cells into skin cells
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A new study published in
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The research tracks the transformation of genetically manipulated cells into melanocytes, which are responsible for the production of skin pigment and essential to the body's auditory system.The study, based on mouse models, was led jointly by Prof. Carmit Levy of the Department of Human Molecular Genetics and Biochemistry at Tel Aviv University's Sackler School of Medicine and Dr. Jacob Hanna of the Weizmann Institute of Science."When cells develop, they differentiate into different organs with varying functions: bone, intestine, brain, and so on," Prof. Levy says. "Our study proves, for the first time, that this process is not irreversible. We can turn back the clock and transform a mature cell that already plays a definite role in the body into a cell of a completely different kind."The applications of this are endless -- from transplants, which would eliminate long waiting lists and eliminate the common problem of immune system rejection of 'foreign' organs; to maybe one day curing deafness: taking any cell in the body and transforming it into melanocytes to aid in the restoration of hearing. The possibilities are really beyond the scope of the imagination," Prof. Levy continues.The scientists took cells from different parts of the mouse -- stomach, intestine, connective tissue, heart and brain -- and placed these cells in a solution activating the genetic switch MITF (Microphthalmia-associated transcription factor), which is responsible for the production of melanocytes. Through this method, a stomach cell was turned into a skin cell."All of our genes are in all our cells, but genetic mechanisms allow them to manifest in the appropriate place while remaining dormant everywhere else," says Dr. Hanna. "Each cell has a kind of 'switch.' We activated the MITF switch to create melanocytes from cells designated for other purposes."The generation of an entire genetically manipulated mouse is new and affords a scientific breakthrough that may save lives in the future, Prof. Levy concludes. "Future developments based on this method may enable the transformation of one tissue taken from the patient's own body into another tissue to replace the damaged organ, for example. Curing hearing loss is also a promising direction for this research because melanocytes are essential to our auditory system."
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Genetically Modified
| 2,017 |
October 17, 2017
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https://www.sciencedaily.com/releases/2017/10/171017091903.htm
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'Hiding in plain sight:' Discovery raises questions over scale of overlooked biodiversity
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Scientists have used cutting-edge DNA technology and museum samples collected over the past two centuries to reveal a new species of diving beetle living in streams around the Mediterranean.
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But academics from the University of Plymouth and the Institute of Evolutionary Biology in Barcelona have now shown what was long thought to be one common species is actually two.Using DNA sequence data and detailed analysis of morphology, they have described a new species -- David Bilton, Professor of Aquatic Biology at the University of Plymouth, led the study having first collected samples of the beetles in the late 1990s.He said: "We began studying the genetics of these beetles to try to understand how animals had colonised islands -- we certainly weren't looking for, or expecting, a new species. The new species was in fact 'hiding in plain sight', since a study of material from a number of European museums revealed specimens of the newly identified species had been collected as long ago as the mid-19th century. But without the genetic data, these had all been thought to belong to the one, common, species.Genetic data on more specimens, and a careful study of the appearance of the beetles themselves, has now allowed scientists to identify subtle, but consistent, ways in which the two species differ. This includes the precise sculpturing of their wing cases, with lepidoptera's appearing rather like the interlocking scales on a butterfly's wing, hence its name.Dating based on the DNA analyses suggests that Professor Bilton added: "This is only one new species, but it's been hiding amongst one of the largest, most obvious freshwater species in Europe, in an area we have supposedly explored pretty thoroughly. The fact that discoveries like ours are still possible emphasizes how little we know about the biodiversity of this planet, something which should be a major priority, particularly when so much of it is threatened by human activity. To effectively conserve biodiversity, we need to understand what's out there, because ignorance can lead to the wrong decisions being made about species and habitats."
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Genetically Modified
| 2,017 |
October 12, 2017
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https://www.sciencedaily.com/releases/2017/10/171012091004.htm
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New way to prevent genetically engineered and unaltered organisms from producing offspring
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A major obstacle to applying genetic engineering to benefit humans and the environment is the risk that organisms whose genes have been altered might produce offspring with their natural counterparts, releasing the novel genes into the wild. Now, researchers from the University of Minnesota's BioTechnology Institute have developed a promising way to prevent such interbreeding. The approach, called "synthetic incompatibility," effectively makes engineered organisms a separate species unable to produce viable offspring with their wild or domesticated relatives.
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Synthetic incompatibility has applications in controlling or eradicating invasive species, crop pests and disease-carrying insects as well as preventing altered genes from escaping from genetically modified crops into other plant populations. The results were published online in the journal The technology uses a new class of molecular tools called "programmable transcription factors" that make it possible to control which genes are turned on and which genes are turned off in an organism. If an engineered organism mates with a wild counterpart, the transcription factors render the offspring unable to survive by activating genes that cause their cells to die."This approach is particularly valuable because we do not introduce any toxic genes," said Maciej Maselko, a postdoctoral scholar from Smanski's lab who performed the work. "The genetic incompatibility results from genes already in the organism being turned on at the wrong place or time."The research was done in brewer's yeast, but it can potentially be applied in insects, aquatic organisms and plants using a new gene editing technique known as CRISPR-Cas9. "Other methods to control gene flow, for example disrupting pollen or using a chemical to control reproduction in crops, are very species-specific and change how the crops are propagated. Our approach is expected work in virtually any sexually reproducing organism without changing how they are normally grown," said Michael Smanski, an assistant professor who led the study.Synthetic incompatibility may make it possible to use crops to produce medications as well as food, feed and fuel. It also raises hope for using genetic engineering to control populations of invasive species or pests such as Asian carp in North America and disease-carrying mosquitoes throughout the world.The next step, Smanski said, is to demonstrate the approach can work in organisms other than yeast "We're working on moving into model fish, insects, nematodes and plants," he said.The University of Minnesota College of Biological Sciences seeks to improve human welfare and global conditions by advancing knowledge of the mechanisms of life and preparing students to create the biology of tomorrow.
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Genetically Modified
| 2,017 |
October 10, 2017
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https://www.sciencedaily.com/releases/2017/10/171010105146.htm
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Pest resistance to biotech crops surging
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In 2016, farmers worldwide planted more than 240 million acres (98 million hectares) of genetically modified corn, cotton and soybeans that produce insect-killing proteins from the bacterium Bacillus thuringiensis, or Bt. These Bt proteins kill some voracious caterpillar and beetle pests, but are harmless to people and considered environmentally friendly. While organic farmers have used Bt proteins in sprays successfully for more than half a century, some scientists feared that widespread use of Bt proteins in genetically engineered crops would spur rapid evolution of resistance in pests.
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Researchers at the University of Arizona in Tucson, Arizona have taken stock to address this concern and to discover why pests adapted quickly in some cases but not others. To test predictions about resistance, Bruce Tabashnik and Yves Carriere in the College of Agriculture and Life Sciences analyzed the global data on Bt crop use and pest responses. Their results are published in the current issue of the journal "When Bt crops were first introduced in 1996, no one knew how quickly the pests would adapt," said Tabashnik, a Regents' Professor and head of the UA Department of Entomology. "Now we have a cumulative total of over 2 billion acres of these crops planted during the past two decades and extensive monitoring data, so we can build a scientific understanding of how fast the pests evolve resistance and why."The researchers analyzed published data for 36 cases representing responses of 15 pest species in 10 countries on every continent except Antarctica. They discovered resistance that substantially reduced the efficacy of the Bt crops in the field in 16 cases as of 2016, compared with only three such cases by 2005. In these 16 cases, pests evolved resistance in an average time of just over five years."A silver lining is that in 17 other cases, pests have not evolved resistance to Bt crops," Tabashnik said, adding that some crops continue to remain effective after 20 years. The remaining three cases are classified as "early warning of resistance," where the resistance is statistically significant, but not severe enough to have practical consequences.Fred Gould, Distinguished Professor of Entomology at North Carolina State University and leader of the 2016 National Academy of Sciences study on genetically engineered crops, commented, "This paper provides us with strong evidence that the high-dose/refuge strategy for delaying resistance to Bt crops is really working. This will be critically important information as more crops are engineered to produce Bt toxins."According to the paper, both the best and worst outcomes support predictions from evolutionary principles."As expected from evolutionary theory, factors favoring sustained efficacy of Bt crops were recessive inheritance of resistance in pests and abundant refuges," Carriere said.Refuges consist of standard, non-Bt plants that pests can eat without exposure to Bt toxins. Planting refuges near Bt crops reduces the chances that two resistant insects will mate with each other, making it more likely they will breed with a susceptible mate. With recessive inheritance, matings between a resistant parent and a susceptible parent yield offspring that are killed by the Bt crop."Computer models showed that refuges should be especially good for delaying resistance when inheritance of resistance in the pest is recessive," Carriere explained. The value of refuges has been controversial, and the Environmental Protection Agency has relaxed its requirements for planting refuges in the U.S."Perhaps the most compelling evidence that refuges work comes from the pink bollworm, which evolved resistance rapidly to Bt cotton in India, but not in the U.S.," Tabashnik said.In the southwestern U.S., farmers collaborated with academia, industry, EPA scientists, and the U.S. Department of Agriculture to implement an effective refuge strategy. Although India similarly required a refuge strategy, farmer compliance was low."Same pest, same crop, same Bt proteins, but very different outcomes," said Tabashnik.The new study revealed that pest resistance to Bt crops is evolving faster now than before, primarily because resistance to some Bt proteins causes cross-resistance to related Bt proteins produced by subsequently introduced crops.An encouraging development is the recent commercialization of biotech crops producing a novel type of Bt protein called a vegetative insecticidal protein, or Vip. All other Bt proteins in genetically engineered crops are in another group, called crystalline, or Cry, proteins. Because these two groups of Bt proteins are so different, cross-resistance between them is low or nil, according to the authors of the study.Yidong Wu, Distinguished Professor in the College of Plant Protection at Nanjing Agricultural University in China, said, "This review provides a timely update on the global status of resistance to Bt crops and unique insights that will help to improve resistance management strategies for more sustainable use of Bt crops."Although the new report is the most comprehensive evaluation of pest resistance to Bt crops so far, Tabashnik indicated it represents only the beginning of using systematic data analyses to enhance understanding and management of resistance."These plants have been remarkably useful, and resistance has generally evolved slower than most people expected," he said. "I see these crops as an increasingly important part of the future of agriculture. The progress made provides motivation to collect more data and to incorporate it in planning future crop deployments.""We've also started exchanging ideas and information with scientists facing related challenges, such as resistance to herbicides in weeds and resistance to drugs in cancer cells," Tabashnik said.But will farmers ever be able to prevent resistance altogether? Tabashnik doesn't think so."We always expect the pests to adapt. However, if we can delay resistance from a few years to a few decades, that's a big win."
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Genetically Modified
| 2,017 |
October 10, 2017
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https://www.sciencedaily.com/releases/2017/10/171010105717.htm
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Gene drives have the potential to suppress mosquito populations, but resistant mosquitoes crop up
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Researchers successfully built a gene drive to reduce female fertility in the mosquito that spreads malaria, but mutations gradually arose that blocked the spread of the new genes. Tony Nolan of Imperial College London, UK, and colleagues report these findings in a new paper in
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Gene drives have incredible potential for controlling insects that carry disease or destroy crops, by altering genes in ways that reduce population size or prevent the insect from spreading a parasite, virus or bacterium. In synthetic gene drives, scientists engineer genes that will quickly spread through a population because they are preferentially inherited by the offspring, even if they have a negative impact on the insect. Nolan and colleagues previously generated a synthetic gene drive in captive The study is the first to document the rise of mutations that make mosquitoes resistant to a gene drive, due to natural selection. These findings will allow researchers to make better predictions of how a gene drive will proceed and to improve the design of future gene drives to decrease the likelihood of resistance.Tony Nolan adds: "Reducing the numbers of mosquito vectors has been the most effective tool to date for the control of malaria, so self-sustaining gene drives designed with this purpose have great potential. However gene drives are not a silver bullet and just like antibiotics can select for resistance in bacteria, gene drives can be susceptible to resistance at their target site. The novelty of this study is not that resistance emerges -- we have been planning strategies to deal with this from the start -- but that it documents the way it emerges and the way it is selected over generations. This work will help a lot in planning for and managing the emergence of resistance."
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Genetically Modified
| 2,017 |
October 3, 2017
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https://www.sciencedaily.com/releases/2017/10/171003144506.htm
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Designer biosensor can detect antibiotic production by microbes
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Researchers from North Carolina State University have engineered designer biosensors that can detect antibiotic molecules of interest. The biosensors are a first step toward creating antibiotic-producing "factories" within microbes such as
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Macrolides are a group of naturally occurring small molecules that can have antibiotic, antifungal or anticancer effects. The antibiotic erythromycin is one example -- it is a macrolide produced by soil-dwelling bacteria. Researchers are interested in using these natural antibiotics and the microbes that produce them in order to develop new antibiotics; however, microbes that produce antibiotic macrolides only make small amounts of a limited variety of antibiotics."Our ultimate goal is to engineer microbes to make new versions of these antibiotics for our use, which will drastically reduce the amount of time and money necessary for new drug testing and development," says Gavin Williams, associate professor of bio-organic chemistry at NC State and corresponding author of a paper describing the research. "In order to do that, we first need to be able to detect the antibiotic molecules of interest produced by the microbes."Williams and his team used a naturally occurring molecular switch -- a protein called MphR -- as their biosensor. In The researchers created a large library of MphR protein variants and screened them for the ability to switch on production of a fluorescent green protein when they were in the presence of a desired macrolide. They tested the variants against erythromycin, which MphR already recognizes, and found that some of the MphR variants improved their detection ability tenfold. They also successfully tested the variants against macrolides that were not closely related to erythromycin, such as tylosin."Essentially we have co-opted and evolved the MphR sensor system, increasing its sensitivity in recognizing the molecules that we're interested in," says Williams. "We know that we can tailor this biosensor and that it will detect the molecules we're interested in, which will enable us to screen millions of different strains quickly. This is the first step toward high-throughput engineering of antibiotics, where we create vast libraries of genetically modified strains and variants of microbes in order to find the few strains and variants that produce the desired molecule in the desired yield."The research appears in
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Genetically Modified
| 2,017 |
October 2, 2017
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https://www.sciencedaily.com/releases/2017/10/171002084828.htm
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GM soybean oil causes less obesity and insulin resistance but is harmful to liver function
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Researchers at the University of California, Riverside have tested a genetically-modified (GM) soybean oil used in restaurants and found that while it induces less obesity and insulin resistance than conventional soybean oil, its effects on diabetes and fatty liver are similar to those of conventional soybean oil.
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Soybean oil is the major vegetable cooking oil used in the United States, and its popularity is on the increase worldwide. Rich in unsaturated fats, especially linoleic acid, soybean oil induces obesity, diabetes, insulin resistance, and fatty liver in mice.UC Riverside researchers tested Plenish®, a genetically-modified (GM) soybean oil released by DuPont in 2014. Plenish is engineered to have low linoleic acid, resulting in an oil similar in composition to olive oil, the basis of the Mediterranean diet and considered to be healthful.The study, published today in The study also compares both conventional soybean oil and Plenish to coconut oil, which is rich in saturated fatty acids and causes the least amount of weight gain among all the high-fat diets tested."We found all three oils raised the cholesterol levels in the liver and blood, dispelling the popular myth that soybean oil reduces cholesterol levels," said Frances Sladek, a professor of cell biology, who led the research project.Next, the researchers compared Plenish to olive oil. Both oils have high oleic acid, a fatty acid believed to reduce blood pressure and help with weight loss."In our mouse experiments, olive oil produced essentially identical effects as Plenish -- more obesity than coconut oil, although less than conventional soybean oil -- and very fatty livers, which was surprising as olive oil is typically considered to be the healthiest of all the vegetable oils," said Poonamjot Deol, an assistant project scientist working in Sladek's lab and the co-first author of the research paper. "Plenish, which has a fatty acid composition similar to olive oil, induced hepatomegaly, or enlarged livers, and liver dysfunction, just like olive oil."Sladek explained that some of the negative metabolic effects of animal fat that researchers often see in rodents could actually be due to high levels of linoleic acid, given that most U.S. farm animals are fed soybean meal."This could be why our experiments are showing that a high-fat diet enriched in conventional soybean oil has nearly identical effects to a diet based on lard," she said.The researchers further speculate that the increased consumption of soybean oil in the U.S. since the 1970s could be a contributing factor to the obesity epidemic. According to the Centers for Disease Control and Prevention, 35 percent of adults are obese. In some ethnic groups, however, such as Hispanics and African-Americans, between 42 percent and 48 percent of the population is obese. Obesity, officially designated by the American Medical Association in 2013 as a disease, is linked to diabetes, heart disease, and cancer."Our findings do not necessarily relate to other soybean products like soy sauce, tofu, or soy milk -- products that are largely from the water-soluble compartment of the soybean; oil, on the other hand, is from the fat-soluble compartment," Sladek said. "More research into the amounts of linoleic acid in these products and others is needed."Linoleic acid is an essential fatty acid. All humans and animals must obtain it from their diet."But just because it is essential does not necessarily mean it is good to have more of it in your diet," Deol said. "Our bodies need just 1-to-2 percent linoleic acid from our diet, but Americans, on average, have 8-to-10 percent linoleic acid in their diets."Deol and Sladek recommend avoiding conventional soybean oil as much as possible."This might be difficult as conventional soybean oil is used in most restaurant cooking and found in most processed foods," Deol said. "One advantage of Plenish is that it generates fewer transfats than conventional soybean oil.""But with its effects on the liver, Plenish would still not be my first choice of an oil," Sladek said. "Indeed, I used to use exclusively olive oil in my home, but now I substitute some of it for coconut oil. Of all the oils we have tested thus far, coconut oil produces the fewest negative metabolic effects, even though it consists nearly entirely of saturated fats. Coconut oil does increase cholesterol levels, but no more than conventional soybean oil or Plenish."The researchers have not examined the cardiovascular effects of coconut oil."As a result, we do not know if the elevated cholesterol coconut oil induces is detrimental," Sladek said. "The take-home message is that it is best not to depend on just one oil source. Different dietary oils have far reaching and complex effects on metabolism that require additional investigation."The study builds on an earlier study by the researchers that compared soybean oil to a high fructose diet and found soybean oil causes more obesity and diabetes than coconut oil.Next, the researchers, who found a positive correlation between oxylipins (oxidized fatty acids) in linoleic acid and obesity, plan to determine whether the oxylipins cause obesity, and, if so, by what mechanism. They will also study the effects of conventional and GM soybean oil on intestinal health.
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Genetically Modified
| 2,017 |
September 28, 2017
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https://www.sciencedaily.com/releases/2017/09/170928145418.htm
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Disease resistance successfully spread from modified to wild mosquitoes
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Using genetically modified (GM) mosquitoes to reduce or prevent the spread of infectious diseases is a new but rapidly expanding field of investigation. Among the challenges researchers face is ensuring that GM mosquitoes can compete and mate with their wild counterparts so the desired modification is preserved and spread in the wild population. Investigators at Johns Hopkins University have engineered GM mosquitoes to have an altered microbiota that suppresses human malaria-causing parasites. These GM mosquitos preferred to mate with wild mosquitoes and passed along the desired protection to many generations of offspring.
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The research was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.The researchers genetically modified The group also showed that the change in the microbiota resulted in a mating preference among the GM and wild mosquitoes. GM males showed a preference for wild females and wild males preferred GM females; these preferences contributed to the spread of the desired protective trait within the mosquito population.The authors note that work was conducted in a laboratory setting and that more research is needed to determine if what they observed in the laboratory also will occur under natural conditions. Nevertheless, the study suggests that mosquitoes can be genetically modified to compete in nature with wild populations and spread resistance to the malaria-causing parasite. If implemented, this strategy could eventually result in decreased disease transmission to humans.
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Genetically Modified
| 2,017 |
September 28, 2017
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https://www.sciencedaily.com/releases/2017/09/170928142121.htm
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Smart molecules trigger white blood cells to become better cancer-eating machines
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A team of researchers has engineered smart protein molecules that can reprogram white blood cells to ignore a self-defense signaling mechanism that cancer cells use to survive and spread in the body. Researchers say the advance could lead to a new method of re-engineering immune cells to fight cancer and infectious diseases. The team successfully tested this method in a live cell culture system.
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The work was led by bioengineering professors Peter Yingxiao Wang and Shu Chien with collaborating professors Victor Nizet and Xiangdong Xu, all at the University of California San Diego, along with researchers from the University of Illinois at Urbana-Champaign. The team published their work this month in The smart proteins, called "iSNAPS" (integrated sensing and activating proteins), are designed to detect precise molecular signals in live cells and in response, act upon those signals to enable the cells to fight disease or perform other beneficial functions. This study is the first to demonstrate how both sensing and activating capabilities can be combined into a single molecule, Wang said.The researchers inserted their iSNAPS into a type of white blood cells called macrophages and demonstrated that they dramatically enhanced the macrophages' ability to engulf and destroy rapidly dividing cancer cells.Macrophages are white blood cells that play a significant role in the immune system. Part of their task is to remove foreign particles and harmful organisms such as pathogens and cancer cells by digesting them. When a macrophage binds to a cancer cell or other foreign invader, surface proteins on the macrophage called Fc gamma receptors send out an "eat me" signal that prompts the macrophage to engulf and destroy the invader.However, cancer cells have a special protection mechanism that contributes to their deadly disease potential. They have a surface protein called CD47 that interacts with the macrophage's SIRP-alpha surface protein to send out a negating "don't eat me" signal.The secret to getting the iSNAP technology to work involves reconfiguring the battleground between the cancer cells and the immune system. The iSNAPS essentially rewire macrophages to override this "don't eat me" signal and interpret it as an "eat me" signal. The iSNAPs have a sensing component that detects the key molecular event that occurs inside a macrophage when its SIRP-alpha surface protein interacts with CD47 on the cancer cell. In response, the iSNAPS have an activating component that immediately transforms to produce a green/yellow light signal, giving researchers a way to visualize the molecular activity through a microscope. The activating component is also triggered to release an enzyme that initiates a cascade of events that enables the macrophage to engulf the cancer cell. "What's noteworthy is that this response time is very fast -- we believe it happens within seconds to minutes" Wang said.In their experiments, the researchers mixed their engineered macrophages with cancer cells in culture dishes and observed the activity through a microscope. The macrophages were able to engulf most of the cancer cells tested. As a control experiment, the researchers used macrophages containing disabled iSNAPS, which have sensing capability but no activating capability. They observed that these macrophages could bind and detect the presence of the cancer cells but not eat them.Wang noted that the iSNAPS design could in principle be modified for other uses, such as re-engineering immune cells to kill bacteria. They could also be applied to other immune cell types such as T cells for multi-pronged cancer therapy. Moving forward, the team is planning to test the iSNAPS in mice to see how they would perform
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Genetically Modified
| 2,017 |
September 28, 2017
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https://www.sciencedaily.com/releases/2017/09/170928121651.htm
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Fluorine-containing molecules from cell cultures
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Natural organic compounds that contain fluorine are rare because living organisms -- with a few exceptions -- do not produce them. American scientists have now genetically engineered a microbial host for organofluorine metabolism, allowing it to produce a fluoridated intermediate known as a diketide. As reported in the journal
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Unlike nature, chemists use fluorine often. Teflon coatings for pans and water-repellent Gore-Tex jackets, both based on polytetrafluoroethylene, immediately spring to mind. Fluorine is also found in many agrochemicals, and about 20-30% of modern pharmaceuticals, ranging from antimalarial and cytostatic drugs to inhalation anesthetics, blood substitutes, and liquid ventilation agents. Organofluorine molecules are also used in liquid crystals for displays, as well as ozone-friendly refrigerants and propellants.Given the potential for living systems to produce highly complex chemical compounds, researchers working with Michelle C.Y. Chang at the University of California, Berkeley (USA), aimed to manipulate the biosynthetic machinery in cells to use simple fluorinated building blocks to make new organofluorine target molecules.To achieve this, they introduced genes that code for three particularly efficient enzymes from a variety of other microorganisms into the bacterium, The researchers introduced yet another gene for an enzyme used by many bacteria to make polyhydroxyalkanoates (PHAs), which are polyesters used to store carbon and energy. Biodegradable PHAs are used in the production of bioplastics for applications like food packaging and medical implants. The new, genetically engineered microorganisms incorporated the fluorinated diketides into the PHAs they produced, generating polymers containing 5 to 15 % fluorinated monomers. The fluorinated bioplastics were less brittle than fluorine-free PHAs. Controlled incorporation of fluorinated monomers could allow for targeted variation of the properties of bioplastics.The researchers also hope to use the key component fluoromalonyl coenzyme A to produce a broad spectrum of small fluorinated molecules in living cells for pharmaceutical applications.
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Genetically Modified
| 2,017 |
September 27, 2017
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https://www.sciencedaily.com/releases/2017/09/170927133827.htm
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Haplobank: A biobank of reversible mutant embryonic stem cells
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Scientist at IMBA developed a biobank of revertible, mutant embryonic stem cells, published in the current issue of Nature. This cell bank -- called Haplobank -- contains over 100,000 mutated, conditional mouse embryonic stem cell lines, targeting about 70% of the protein-coding genome.
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Genetic screens have revolutionized our understanding of biological processes and disease mechanisms. Recent technical advances have broadened the available approaches for disrupting gene function in a cell population prior to screening, from chemical and insertional mutagenesis to RNA interference, and, most recently, CRISPR-mediated genome editing. However, RNA interference and CRISPR-mediated gene targeting often suffer from poor efficiency and off-target effects. In addition, most mutagenesis approaches are not reversible -- making it difficult to rigorously control for the frequent genetic and epigenetic differences between ostensibly identical cells. These issues can confound the reproducibility, interpretation and overall success of genetic screens.Major concerns about scientific reproducibility and rigor have emerged in recent years. Amgen and Bayer, as well as The Reproducibility Initiative, have been unable to replicate many high-profile cancer studies. Indeed, it is not uncommon to obtain different results from experiments with the same cell line in two different laboratories. These inconsistencies can arise for various reasons. Regardless, irreproducible results waste money, damage the credibility of science and scientists, and delay or undo progress, including the development of effective therapies.To overcome these problems, the Penninger lab at the IMBA developed a biobank of revertible, mutant embryonic stem cells, published in the current issue of Nature. This cell bank -- called Haplobank -- contains over 100,000 mutated, conditional mouse embryonic stem cell lines, targeting about 70% of the protein-coding genome (almost 17,000 genes). "Haplobank is available to all scientists, and represents the largest ever library of hemizyogous mutant embryonic stem cell lines to date. The resource overcomes issues arising from clonal variability, because mutations can be repaired in single cells and at whole genome scale," explains Ulrich Elling, first and corresponding author of the current publication in Nature.As a proof-of-principle, the authors performed a genetic screen to uncover factors required for infection with rhinovirus -- the cause of the common cold. They discovered that rhinovirus requires a previously unknown host cell factor, phospholipase A2G16 (PLA2G16), to kill cells. Further, they showed that a specific domain of PLA2G16 is required for infection and may be an attractive drug target. Interestingly, PLA2G16 was also shown recently to be necessary for successful infection by related viruses, including poliovirus.In another proof-of-principle screen, the authors leveraged the pluripotent potential of embryonic stem cells by differentiating them into blood vessel organoids. The formation of blood vessels (angiogenesis) is critical for development and for tissue maintenance, as well as for diseases like cancer. The authors screened candidate angiogenesis genes that were represented in Haplobank, and discovered multiple novel factors that affect blood vessel growth in organoids. Importantly, they observed a strong variability between independent clones, highlighting the advantage of repairable mutagenesis for comparing mutants with their genetically repaired sister clones."Haplobank can be used for screens to make entirely new insights into biology and health. Importantly -- because gene knockouts can be repaired in our embryonic stem clones -- this resource also enables well-controlled, robust and reproducible validation experiments. We feel this is a critical point and contribution, given the current efforts to improve the rigor of scientific research." Says Josef Penninger, IMBA Director and last author.
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Genetically Modified
| 2,017 |
September 26, 2017
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https://www.sciencedaily.com/releases/2017/09/170926125128.htm
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Scientists unlock mysteries of how Ebola uses people's immune defenses to cause infection
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Scientists from The University of Texas Medical Branch at Galveston have gained new insight into how the Ebola virus uses the body's natural defenses to speed the rate of infection and unleash its lethal disease, according to a new report in
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When someone is infected with the Ebola virus, part of the reason that the resulting disease is so severe is because the virus causes parts of the immune system to malfunction. T-cells, which are a specialized type of white blood cells that seek and destroy virus-infected cells, are particularly vulnerable to the Ebola virus."In this study, we demonstrated the central role of a T-cell protein called Tim-1 in the development of Ebola virus disease," said senior author Alexander Bukreyev, a UTMB virologist in the departments of pathology and microbiology and immunology. "Mice that were genetically engineered without Tim-1 became less ill when infected with Ebola virus and only one died, whereas all of the unmodified mice succumbed."Bukreyev noted that the mice without Tim-1 had only slightly lower levels of the virus in their bodies compared with unmodified mice, suggesting that the Ebola virus needs the Tim-1 cells to spread infection. The Tim-1 deficient mice's immune system used a different virus-fighting strategy that protected them.A series of biological analyses of the mice with Tim-1 and immune cells isolated from human donors showed that Ebola virus directly binds to T-cells through Tim-1 protein binding and causes massive inflammation that thwarts the immune system. The severity of inflammatory immune reaction is consistently linked with the intensity of the disease and risk of death from Ebola."Understanding how the invading Ebola virus impacts the host's immune system is a very important step in developing targeted therapies for Ebola virus disease," said Bukreyev. "The findings of this study indicate that drugs that block Tim-1 could be a potential new treatment for people with Ebola.""If we can find a way to limit the inflammatory response known as the 'cytokine storm' during Ebola infection, we can potentially improve disease outcome" said Patrick Younan, the lead author of the paper. "Controlling and successfully balancing the immune response following Ebola virus infection is greatly important for reducing symptoms and fatal outcomes," said Mathieu Iampietro, the co-lead author of the paper.
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Genetically Modified
| 2,017 |
September 18, 2017
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https://www.sciencedaily.com/releases/2017/09/170918093340.htm
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Cells programmed like computers to fight disease
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Led by Professor Alfonso Jaramillo in the School of Life Sciences, new research has discovered that a common molecule -- ribonucleic acid (RNA), which is produced abundantly by humans, plants and animals -- can be genetically engineered to allow scientists to program the actions of a cell.
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As well as fighting disease and injury in humans, scientists could harness this technique to control plant cells and reverse environmental and agricultural issues, making plants more resilient to disease and pests.RNAs carry information between protein and DNA in cells, and Professor Jaramillo has proved that these molecules can be produced and organised into tailor-made sequences of commands -- similar to codes for computer software -- which feed specific instructions into cells, programming them to do what we want.Much like a classic Turing computer system, cells have the capacity to process and respond to instructions and codes inputted into their main system, argues Professor Jaramillo.Similar to software running on a computer, or apps on a mobile device, many different RNA sequences could be created to empower cells with a 'Virtual Machine', able to interpret a universal RNA language, and to perform specific actions to address different diseases or problems.This will allow a novel type of personalised and efficient healthcare, allowing us to 'download' a sequence of actions into cells, instructing them to execute complex decisions encoded in the RNA.The researchers made their invention by first modelling all possible RNA sequence interactions on a computer, and then constructing the DNA encoding the optimal RNA designs, to be validated on bacteria cells in the laboratory.After inducing the bacterial cells to produce the genetically engineered RNA sequences, the researchers observed that they had altered the gene expression of the cells according to the RNA program -- demonstrating that cells can be programmed with pre-defined RNA commands, in the manner of a computer's microprocessor.Professor Alfonso Jaramillo, who is part of the Warwick Integrative Synthetic Biology Centre, commented:"The capabilities of RNA molecules to interact in a predictable manner, and with alternative conformations, has allowed us to engineer networks of molecular switches that could be made to process arbitrary orders encoded in RNA."Throughout the last year, my group has been developing methodologies to enable RNA sensing the environment, perform arithmetic computations and control gene expression without relying on proteins, which makes the system universal across all living kingdoms."The cells could read the RNA 'software' to perform the encoded tasks, which could make the cells detect abnormal states, infections, or trigger developmental programs."
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Genetically Modified
| 2,017 |
September 6, 2017
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https://www.sciencedaily.com/releases/2017/09/170906114614.htm
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This one goes up to 11: Researchers crack code for genetic 'control dials'
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When a gene is switched on, various stretches of DNA nearby act as 'control dials', influencing the level of activity and the amount of gene product that is made. Using Mycoplasma pneumoniae bacteria as a model, CRG director Professor Luis Serrano and his team developed a rapid way of scanning through many thousands of randomly-generated DNA sequences in search of those that could efficiently activate a 'reporter' gene.
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The researchers used the new technique, known as ELM-seq, to find DNA sequences that strongly increase the levels of transcription -- the process by which a gene is 'read' to produce an intermediate message known as RNA. They also searched for sequences that enhance the efficiency of translation, when RNA messages are interpreted to build products such as protein molecules. The patented ELM-seq method relies on indirectly measuring the activity of a gene encoding a protein that adds a specific chemical 'tag' on to DNA. If the gene is more active it will leave more tags on the DNA. These tags are detected and measured using a sensitive DNA analysis technique known as massive, parallel sequencing, providing a quantitative readout of the gene's activity levels.Publishing their findings in the open-access journal "Previous techniques that have been used to investigate DNA control sequences usually rely on sorting cells one by one and measuring gene activity in each of them," says Dr Eva Yus, lead author of the paper. "However, our new approach uses cutting-edge DNA sequencing technology to precisely measure the effects of thousands of sequences on gene activity at the same time.""If we want to use bacteria or other cells for biotechnology applications, we need to engineer them to make the maximum amount of product. But it's very difficult if we don't have information about the optimum sequences for controlling genes," says Dr Jae-Seong Yang, co-author of the study.Because "We now have a big range of control sequences we can use to adjust the levels of the proteins we want to produce in the lungs -- like a toolkit we can use to control gene activity," Professor Serrano explains. "In addition, this technique is a very cheap and fast way of finding the sequences governing transcription and translation, and could be used for any biotechnology application or organism."
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Genetically Modified
| 2,017 |
August 30, 2017
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https://www.sciencedaily.com/releases/2017/08/170830141248.htm
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Gut bacteria that 'talk' to human cells may lead to new treatments
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We have a symbiotic relationship with the trillions of bacteria that live in our bodies -- they help us, we help them. It turns out that they even speak the same language. And new research from The Rockefeller University and the Icahn School of Medicine at Mt. Sinai suggests these newly discovered commonalities may open the door to "engineered" gut flora who can have therapeutically beneficial effects on disease.
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"We call it mimicry," says Sean Brady, director of Rockefeller University's Laboratory of Genetically Encoded Small Molecules, where the research was conducted. The breakthrough is described in a paper published this week in the journal In a double-barreled discovery, Brady and co-investigator Louis Cohen found that gut bacteria and human cells, though different in many ways, speak what is basically the same chemical language, based on molecules called ligands. Building on that, they developed a method to genetically engineer the bacteria to produce molecules that have the potential to treat certain disorders by altering human metabolism. In a test of their system on mice, the introduction of modified gut bacteria led to reduced blood glucose levels and other metabolic changes in the animals.The method involves the lock-and-key relationship of ligands, which bind to receptors on the membranes of human cells to produce specific biological effects. In this case, the bacteria-derived molecules are mimicking human ligands that bind to a class of receptors known as GPCRs, for G-protein-coupled receptors.Many of the GPCRs are implicated in metabolic diseases, Brady says, and are the most common targets of drug therapy. And they're conveniently present in the gastrointestinal tract, where the gut bacteria are also found. "If you're going to talk to bacteria," says Brady, "you're going to talk to them right there." (Gut bacteria are part of the microbiome, the larger community of microbes that exist in and on the human body.)In their work, Cohen and Brady engineered gut bacteria to produce specific ligands, N-acyl amides, that bind with a specific human receptor, GPR 119, that is known to be involved in the regulation of glucose and appetite, and has previously been a therapeutic target for the treatment of diabetes and obesity. The bacterial ligands they created turned out to be almost identical structurally to the human ligands, says Cohen, an assistant professor of gastroenterology in the Icahn School of Medicine at Mt. Sinai.Among the advantages of working with bacteria, says Cohen, who spent five years in Brady's lab as part of Rockefeller's Clinical Scholars Program, is that their genes are easier to manipulate than human genes and much is already known about them. "All the genes for all the bacteria inside of us have been sequenced at some point," he says.In past projects, researchers in Brady's lab have mined microbes from soil in search of naturally occurring therapeutic agents. In this instance, Cohen started with human stool samples in his hunt for gut bacteria with DNA he could engineer. When he found them he cloned them and packaged them inside Although they are the product of non-human microorganisms, Brady says it's a mistake to think of the bacterial ligands they create in the lab as foreign. "The biggest change in thought in this field over the last 20 years is that our relationship with these bacteria isn't antagonistic," he says. "They are a part of our physiology. What we're doing is tapping into the native system and manipulating it to our advantage.""This is a first step in what we hope is a larger-scale, functional interrogation of what the molecules derived from microbes can do," Brady says. His plan is to systematically expand and define the chemistry that is being used by the bacteria in our guts to interact with us. Our bellies, it turns out, are full of promise.
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Genetically Modified
| 2,017 |
August 30, 2017
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https://www.sciencedaily.com/releases/2017/08/170830094220.htm
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Nano chip system measures light from single bacterial cell to enable chemical detection
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Researchers at the Hebrew University of Jerusalem have created a nanophotonic chip system using lasers and bacteria to observe fluorescence emitted from a single bacterial cell. To fix the bacteria in place and to route light toward individual bacterial cells, they used V-groove-shaped plasmonic waveguides, tiny aluminum-coated rods only tens of nanometers in diameter. The novel system, described in the journal
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The field of on-chip photonic devices for biological and chemical sensing applications presents many powerful alternatives to conventional analytical techniques for applications ranging from "lab on a chip" to environmental monitoring. However, these sensing schemes rely mainly on off-chip detection and require a cumbersome apparatus, even when measuring only single cells.The Hebrew University team looked for ways to integrate all system components, including light sources and detectors, on-chip at the nanoscale. This would result in a lab-on-chip system that is small, portable and can perform sensing in real-time.To achieve this, they molecularly engineered live bacteria that emit a fluorescent signal in the presence of target compounds. They paired these on-chip with a nanoscale waveguide, which not only served the purpose of guiding light, but also allowed mechanical trapping of individual bacteria within the V-groove.In three different illumination conditions, they experimentally demonstrated the interrogation of an individual Escherichia coli bacterial cell using a nanoscale plasmonic V-groove waveguide. First, they measured the light emitted from a bacterium flowing on top of the nanocoupler in a liquid environment by allowing the fluorescence from the bacterium to be coupled directly into the waveguide through the nanocoupler. Next, a bacterium was mechanically trapped within the V groove waveguide and was excited by laser directly either from the top or through the nanocoupler. In all cases, significant fluorescence was collected from the output nano coupler into the detector.The system worked well both in wet environments, where the bacteria are flowing on top of the waveguide, and in dry conditions, where the bacteria are trapped within the waveguide.The research was led by Prof. Uriel Levy, Director of The Harvey M. Krueger Family Center for Nanoscience and Nanotechnology at the Hebrew University in collaboration with Prof. Shimshon Belkin, at the Hebrew University's Alexander Silberman Institute of Life Sciences, who genetically engineered the bacterial sensors, and Prof. Anders Kristensen from the Danish Technical University, who was in charge of fabricating the V-groove waveguides. Prof. Levy is the Eric Samson Chair in Applied Science and Technology, and Prof. Belkin is the Ministry of Labor and Social Welfare Chair in Industrial Hygiene, at the Hebrew University.Unlike the more traditional plasmonic waveguides consisting of either silver or gold, the choice of aluminum was instrumental for being able to guide the fluorescent light emitted from the bacteria all the way to the output nanocoupler. Furthermore, the waveguide dimensions allow for efficient mechanical trapping of the bacteria and the multimode characteristics may become instrumental in gathering more information, e.g., on the specific position and orientation of the bacteria.The results provide a clear indication of the feasibility of constructing a hybrid bioplasmonic system using live cells. Future work will include the construction of waveguide network, diversifying the system to incorporate different types of bacterial sensors for the detection of various biological or chemical analytes.
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Genetically Modified
| 2,017 |
August 15, 2017
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https://www.sciencedaily.com/releases/2017/08/170815111115.htm
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Rhapsody in red violet
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Color in the plant kingdom is not merely a joy to the eye. Colored pigments attract pollinating insects, they protect plants against disease, and they confer health benefits and are used in the food and drug industries. A new study conducted at the Weizmann Institute of Science, published in the
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Betalains are made by cactus fruit, flowers such as bougainvillea and certain edible plants -- most notably, beets. They are relatively rare in nature, compared to the two other major groups of plant pigments, and until recently, their synthesis in plants was poorly understood. Prof. Asaph Aharoni of Weizmann's Plant and Environmental Sciences Department and Dr. Guy Polturak, then a research student, along with other team members, used two betalain-producing plants -- red beet (To test their findings they genetically engineered yeast to produce betalains. They then tackled the ultimate challenge: reproducing betalain synthesis in edible plants that do not normally make these pigments.The success announced itself in living color. The researchers produced potatoes, tomatoes and eggplants with red-violet flesh and skin. They also managed to control the exact location of betalain production by, for example, causing the pigment to be made only in the fruit of the tomato plant but not in the leaves or stem.Using the same approach, the scientists caused white petunias to produce pale violet flowers, and tobacco plants to flower in hues varying from yellow to orange pink. They were able to achieve a desired hue by causing the relevant genes to be expressed in different combinations during the course of betalain synthesis. These findings may be used to create ornamental plants with colors that can be altered on demand.But a change in color was not the only outcome. Healthy antioxidant activity was 60 percent higher in betalain-producing tomatoes than in average ones. "Our findings may in the future be used to fortify a wide variety of crops with betalains in order to increase their nutritional value," says Aharoni.An additional benefit is that the researchers discovered that betalains protect plants against gray mold, The scientists had produced versions of betalain that do not exist in nature. "Some of these new pigments may potentially prove more stable than the naturally occurring betalains," says Polturak. "This can be of major significance in the food industry, which makes extensive use of betalains as natural food dyes, for example, strawberry yogurts."Furthermore, the findings of the study may be used by the drug industry. When plants start manufacturing betalains, the first step is conversion of tyrosine into an intermediate product, the chemical called L-dopa. Not only is this chemical itself used as a drug, it also serves as a starting material in the manufacture of additional drugs, particularly opiates such as morphine. Plants and microbes engineered to convert tyrosine into L-dopa may therefore serve as a source of this valuable material.
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Genetically Modified
| 2,017 |
August 10, 2017
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https://www.sciencedaily.com/releases/2017/08/170810120435.htm
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New methods for analyzing gene function
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Scientists at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) have developed new methods to produce and analyze genetic mosaics. In these mosaics, tissues contain various groups of cells with different known genotypes, permitting study of the differences that these genotypes generate in cell behavior. The new methods, published today in
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The ability to modify gene activity has radically changed approaches to the study of biological processes. Today, most researchers analyze the function of one gene at a time by modifying its activity -- increasing it or eliminating it -- in all or a subset of cells of an organ or animal. With this approach, the understanding of gene function is obtained through the analysis of the changes that a single genetic modification produces in the development, function, or disease of the organ or animal.As lead author Rui Benedito explained, in experimental approaches using inducible genetic mosaics, the induced genetic changes take place only in some cells of the organism (mutant cells), while the other cells remain unaltered (normal cells). "The use of inducible genetic mosaics is very important because it enables us to study how cells with different genotypes behave in the same environment, so that any differences can be attributed to the induced genetic alteration." This approach to the study of gene function is often more precise and informative than the use of classical genetics, in which modification of the target gene in all cells of the organism can generate secondary alterations that cannot be controlled temporally or spatially and that could distort interpretation of the function of the gene in the process under study.Genetic mosaics have been used extensively in the fruit fly due to the ease of performing mitotic recombination in this organism, and have revolutionized the study of gene function and cell biology. However, it has so far been technically much more challenging to induce and analyze genetic mosaics in the mouse, the most widely used model organism in biomedical research.To generate genetic mosaics in mice, scientists in the Molecular Genetics of Angiogenesis lab at the CNIC have developed new molecular biology and transgenesis methods. These methods allow the simultaneous induction, in a single mouse, of multiple mosaic genetic modifications associated with the expression of distinct fluorescent markers that can be detected by high-resolution multispectral microscopy.To make these new genetic tools usable by other research groups, the CNIC team first developed an open-source DNA engineering strategy that greatly simplifies the production of large and complex DNA constructs containing multiple target genes and fluorescent marker genes in frame. The team also developed new CRISPR/Cas9 methods to introduce these DNA molecules into embryonic stem cells or zygotes, simplifying the rapid and reliable generation of transgenic mouse mosaics.With these new genetic tools and transgenic mice, the CNIC team was able to study the function of multiple genes in the same tissue by simultaneous fluorescence microscopy of up to 15 color-coded cell populations, each expressing a unique combination of genes. According to Rui Benedito, "this technology for the first time allows combinations of multiple genetic mosaics to be induced and analyzed in different cells of the same mouse. Because the different cell populations are induced in the same tissue, and can be imaged simultaneously, an analysis of how their behaviors differ can provide precise data and new insights into the function of the genes under study. This approach has real advantages over established procedures for genetic analysis, which require comparison of cells present in different tissues or environments, since the analysis must be done with independent animals that have or do not have a given genetic modification."
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Genetically Modified
| 2,017 |
August 8, 2017
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https://www.sciencedaily.com/releases/2017/08/170808145924.htm
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Multi-nutrient rice against malnutrition
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Nearly every second person eats primarily rice to meet the daily calorie needs. A meal of rice stops the hunger, but contains only very few or none of the essential micronutrients. As a consequence, large segments of the human population are malnourished, especially in Asia and Africa.
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They do not obtain enough iron, zinc and also vitamin A to stay healthy. Insufficient iron intake results in anemia, retards brain development and increases mortality among women and infants. If children are deficient for vitamin A, they can turn blind and their immune system is weakened, often causing infectious diseases such as measles, diarrhea or malaria.To combat malnutrition, ETH researchers led by Ingo Potrykus developed a new rice variety already many years ago that in 2000 became known as "Golden Rice." This was one of the first genetically modified rice varieties in which the researchers could produce beta-carotene, the precursor of vitamin A, in the endosperm of the rice grain. Golden Rice was later improved and is now used in breeding programs in several countries, primarily in Southeast-Asia.To address other micronutrient deficiencies, researchers in the Laboratory of Plant Biotechnology of Professor Gruissem at ETH Zurich and in other countries also developed rice varieties with increased iron levels in the rice and wheat grains, for example.All of the new transgenic rice varieties have one thing in common, however: they can only provide one particular micronutrient. Until to date, combining several micronutrients into one rice plant was a dream that had not been realized.Now a group led by Navreet Bhullar, senior scientist in the Laboratory of Plant Biotechnology at ETH Zurich, report a success in creating a multi-nutrient rice. The results were recently published in the journal The researcher and her PhD student Simrat Pal Singh succeeded in genetically modifying rice plants such that in addition to sufficient levels of iron and zinc, they also produce significant levels of beta-carotene in the endosperm of the grain compared to normal varieties. "Our results demonstrate that it is possible to combine several essential micronutrients -- iron, zinc and beta-carotene -- in a single rice plant for healthy nutrition," explains Bhullar.Scientifically, the success was the engineering of a gene cassette containing four genes for the micronutrient improvement that could be inserted into the rice genome as a single genetic locus. This has the advantage that iron, zinc and beta-carotene levels can be simultaneously increased by genetic crosses in rice varieties of various countries. Otherwise it would be necessary to cross rice lines with the individual micronutrients to reach the improved micronutrient content in rice grains.Bhullar and her PhD students worked several years to establish this proof-of concept. Although the grains of the multi-nutrient rice lines have more beta-carotene than the original japonica rice variety, depending on the lines the beta-carotene content can be ten-fold lower than in Golden Rice 2, the improved variant of Golden Rice."But if one would substitute 70 percent of the currently consumed white rice with the multi-nutrient variety, this could markedly improve vitamin A supplementation already in addition to sufficient iron and zinc in the diet," emphasizes the researcher.The new multi-nutrient rice lines are still in their testing phase. Until now the plants have been grown in the greenhouse and analyzed for their micronutrient content. "We will improve the lines further," says Bhullar. It is planned to test the plants in confined field trials to determine if the micronutrient traits and also agronomic properties are equally robust in the field as they are in the greenhouse.Bhullar hopes that the new rice lines will be tested in the field next year. But she does not know yet when they are ready for production in farmer's fields. "It will probably be five years before the multi-nutrient rice can be used to reduce hidden hunger," she says.
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Genetically Modified
| 2,017 |
August 1, 2017
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https://www.sciencedaily.com/releases/2017/08/170801154342.htm
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Magnetized viruses attack harmful bacteria
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Magnetic nanoparticle clusters have the power to punch through biofilms to reach bacteria that can foul water treatment systems, according to scientists at Rice University and the University of Science and Technology of China.
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The nanoclusters developed through Rice's Nanotechnology-Enabled Water Treatment (NEWT) Engineering Research Center carry bacteriophages -- viruses that infect and propagate in bacteria -- and deliver them to targets that generally resist chemical disinfection.Without the pull of a magnetic host, these "phages" disperse in solution, largely fail to penetrate biofilms and allow bacteria to grow in solution and even corrode metal, a costly problem for water distribution systems.The Rice lab of environmental engineer Pedro Alvarez and colleagues in China developed and tested clusters that immobilize the phages. A weak magnetic field draws them into biofilms to their targets.The research is detailed in the Royal Society of Chemistry's "This novel approach, which arises from the convergence of nanotechnology and virology, has a great potential to treat difficult-to-eradicate biofilms in an effective manner that does not generate harmful disinfection byproducts," Alvarez said.Biofilms can be beneficial in some wastewater treatment or industrial fermentation reactors owing to their enhanced reaction rates and resistance to exogenous stresses, said Rice graduate student and co-lead author Pingfeng Yu. "However, biofilms can be very harmful in water distribution and storage systems since they can shelter pathogenic microorganisms that pose significant public health concerns and may also contribute to corrosion and associated economic losses," he said.The lab used phages that are polyvalent -- able to attack more than one type of bacteria -- to target lab-grown films that contained strains of Escherichia coli associated with infectious diseases and Pseudomonas aeruginosa, which is prone to antibiotic resistance.The phages were combined with nanoclusters of carbon, sulfur and iron oxide that were further modified with amino groups. The amino coating prompted the phages to bond with the clusters head-first, which left their infectious tails exposed and able to infect bacteria.The researchers used a relatively weak magnetic field to push the nanoclusters into the film and disrupt it. Images showed they effectively killed The researchers noted bacteria may still develop resistance to phages, but the ability to quickly disrupt biofilms would make that more difficult. Alvarez said the lab is working on phage "cocktails" that would combine multiple types of phages and/or antibiotics with the particles to inhibit resistance.
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Genetically Modified
| 2,017 |
August 1, 2017
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https://www.sciencedaily.com/releases/2017/08/170801131215.htm
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Safely releasing genetically modified genes into the wild
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So, you've genetically engineered a malaria-resistant mosquito, now what? How many mosquitos would you need to replace the disease-carrying wild type? What is the most effective distribution pattern? How could you stop a premature release of the engineered mosquitos?
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Releasing genetically engineered organisms into an environment without knowing the answers to these questions could cause irreversible damage to the ecosystem. But how do you answer these questions without field experiments?Applied mathematicians and physicists from Harvard and Princeton Universities used mathematical modeling to guide the design and distribution of genetically modified genes that can both effectively replace wild mosquitos and be safely controlled.The research was recently published in the In the normal course of evolution, any specific trait has only a modest chance of being inherited by offspring. But, with the development of the CRISPR-Cas9 gene editing system, researchers can now design systems that increase the likelihood of inheritance of a desired trait to nearly 100 percent, even if that trait confers a selective disadvantage. These so-called gene drives could replace wild-type genes in short generations.Those powerful systems raise serious safety concerns, such as what happens if a genetically-engineered mosquito accidentally escapes from a lab?"An accidental or premature release of a gene drive construct to the natural environment could damage an ecosystem irreversibly," said Hidenori Tanaka, first author of the paper and graduate student in the Harvard John A. Paulson School of Engineering and Applied Sciences and the Physics Department.To protect against such releases, Tanaka, along with co-authors David Nelson, the Arthur K. Solomon Professor of Biophysics and Professor of Physics and Applied Physics and Howard Stone of Princeton, proposed a narrow range of selective disadvantages that would allow the genes to spread, but only after a critical threshold had been reached.The researchers used nonlinear reaction-diffusion equations to model how genes would move through space. These models provided a framework to develop socially responsible gene drives that balance the genetically-engineered traits with embedded weaknesses that would protect against accidental release and uncontrollable spreading."We can, in effect, construct switches that initiate and terminate the gene drive wave," said Tanaka. "In one, carefully chosen regime, the spatial spreading of the wave starts or progresses only when the parameters of the inoculation exceed critical values that we can calculate."To reach that critical mass, the researchers found that genes needed to be released intensely in a specific region -- like a genetic bomb -- rather than spread thinly throughout larger regions. The genes spread only when the nucleus of the genetic explosion exceeds a critical size and intensity.The researchers also found that by making gene drives susceptible to a compound harmless to wildtype genes, the spread of gene drives can be stopped by barriers like pesticides."This research illustrates how physicists and applied mathematicians can build on results of biological experimentation and theory to contribute to the growing field of spatial population genetics," said Nelson.Next, the researchers hope to understand the impact of genetic mutations and organism number fluctuations on gene drives.
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Genetically Modified
| 2,017 |
July 27, 2017
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https://www.sciencedaily.com/releases/2017/07/170727221729.htm
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Unjustified delays in approving biotech crops take thousands of lives, say researchers
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Scientists, policy makers, and other stakeholders have raised concerns that the approval process for new crops causes delays that are often scientifically unjustified. These delays are not only causing costs via foregone economic benefits, but also lives via foregone calorie supplies for malnourished children. In a new
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Kenya, Uganda and many other African countries had the chance to follow South Africa's example of adopting genetically engineered (GE) crops -- also called GM or biotech crops. The researchers report, if Kenya had adopted GE corn in 2006 -- according to an earlier project this was possible -- between 440 and 4000 lives could theoretically have been saved. Similarly, Uganda had the possibility in 2007 to introduce the black sigatoka resistant banana, thereby potentially saving between 500 and 5500 lives over the past decade. The introduction of Bt cowpea is expected to be in 2017 in Benin, Niger, and Nigeria. The African Agricultural Technology Foundation, an African NGO developing the technology, has already indirectly expressed concerns about reaching this goal by explicitly mentioning the phrase: 'Depending on approvals'. A one-year delay in approval would especially harm Nigeria, as malnourishment is widespread there.The results reported might have underestimated the cost of delay, especially in evaluating the benefit of adopting insect resistant cowpea, as they only consider the energy content of this crop. Further, environmental and health benefits from reduced pesticide use for pest and disease control are not explicitly included.The calculation model the authors used includes economic benefits for producers and consumers as well as the benefits of reduced malnutrition among subsistence farm-households often not explicitly considered in previous studies. The authors also consider the uncertainty policy makers face caused by contradicting statements from lobby groups. They calculate the implicit costs attached. In general, uncertainty about future costs weighs higher than uncertainty about future benefits. One unit of costs needs about 1.5 units of benefits for compensation under uncertainty and explains why policy makers are more responsive to statements about the costs than the benefits of genetically engineered crops. "This explains why those opposing genetically engineered crops have it easier to convince policymakers," explains Justus Wesseler, prof. of Agricultural Economics and Rural Policy at Wageningen University, lead author of the study."Time is money, and lives!, Justus Wesseler concludes. "Reducing the approval time of genetically modified crops results in generating economic gains, potentially contributing to reducing malnutrition and saving lives, and can be an inexpensive strategy for reaching the UN Sustainable Development Goal of eradicating malnutrition by 2030, Justus Wesseler says. "But this might also be important for Europe as it reduces migration."
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Genetically Modified
| 2,017 |
July 27, 2017
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https://www.sciencedaily.com/releases/2017/07/170727104547.htm
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Crops that kill pests by shutting off their genes
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Plants are among many eukaryotes that can "turn off" one or more of their genes by using a process called RNA interference to block protein translation. Researchers are now weaponizing this by engineering crops to produce specific RNA fragments that, upon ingestion by insects, initiate RNA interference to shut down a target gene essential for life or reproduction, killing or sterilizing the insects. The potential of this method is reviewed in
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As chemical pesticides raise concerns over insect resistance, collateral environmental damage, and human exposure risks, transgenic methods are becoming an attractive option for future pest control. For instance, certain strains of corn and cotton have been modified to produce protein toxins from the bacterium "RNA interference-based pest control can provide protection at essentially no cost because once the variety is developed, the plant can just go on using it instead of needing additional applications of insecticide," says co-senior author Ralph Bock, a director at the Max Planck Institute of Molecular Plant Physiology in Germany.An RNA interference strategy could also address environmental and human toxicity questions around chemical pesticides. "When we target a key pest with RNA interference technology, what we are really hoping for is to see a big reduction in overall insecticide use," says co-senior author David Heckel, a director at the Max Planck Institute of Chemical Ecology.Besides application cost and environmental advantages, advocates of the method also point to the flexibility of finding a genetic target and its species specificity. While chemical pesticides such as organophosphates work by overloading an insect's nervous system, a suitable RNA interference target might control something as esoteric, yet indispensable, as cellular protein sorting. Additionally, even when certain target genes are similar across species, optimally designed RNA fragments only inhibit one species and its closest relatives, rather than overwhelming non-threatening insects as some chemical pesticides do.Earlier attempts at pest control through genetic modification that have involved engineering plants to produce proteins toxic to certain insects have prompted concerns about what happens to those proteins when the crop is harvested and ingested. "The objections to transgenic proteins involve concerns about their possible toxicity or allergenicity to humans, but with the RNA interference strategy there's no protein that is made, just some extra RNA," Bock says.RNA interference faces multiple obstacles before it could work for all major crops and their pests. On the plant side, scientists have not yet found a way to transform the chloroplast genomes of cereal grains such as rice and corn, the most direct route to producing enough RNA fragments to eliminate pests at a high rate. On the insect side, prominent pests such as some caterpillars can degrade those fragments, staving off shutdown of the target gene.Bock and Heckel both expect RNA interference technology to be roughly 6 to 7 years away from the field, but they are cautiously optimistic about its potential to change the debate around GMO technology in agriculture. "The Colorado potato beetle is almost worldwide now, even reaching into China," Heckel says. "With such a spread of a main pest that's resistant to insecticides, there's a good case for the development of a transgenic potato to try to halt that trend, and hopefully it will demonstrate enough advantages to overcome the opposition to any and all genetic modifications in crops."
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Genetically Modified
| 2,017 |
July 26, 2017
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https://www.sciencedaily.com/releases/2017/07/170726103015.htm
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Chatting coordinates heterogeneity in bacteria
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Bacterial cells communicate with one another by using chemical signal molecules, which they synthesize and secrete into their surroundings. By this means, the behavior of an entire population can be controlled and coordinated. Biophysicists led by Professor Erwin Frey, who holds the Chair of Biological and Statistical Physics at LMU, have now shown theoretically how this can be accomplished even when only a subset of cells actually emits the requisite signals. The new findings appear in the online journal
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Once the concentration of the relevant signal molecule reaches a certain threshold level in the environment, bacteria can collectively respond by implementing a specific behavioral response, such as the production of bioluminescent compounds or formation of a biofilm. This mechanism is referred to as 'quorum sensing'. The term was derived from the initial belief that all the cells produced the signal, such that its concentration in the environment directly reflected the number of cells present. However, more recent investigations suggest that this is not always the case -- even in genetically identical populations. "We were interested in understanding how such phenotypic heterogeneity can arise in situations in which the cells are genetically identical and are exposed to the same environmental conditions," says Johannes Knebel, one of the joint first authors of the new paper.Frey and his colleagues made use of mathematical models to analyze the complex interplay between ecological factors and population dynamics, and were able to demonstrate that populations can indeed respond in a coordinated fashion to chemical information even when the signal molecules are generated by only a subset of the cells. "For that to occur, two preconditions must be met," says Knebel. "The first is that all the cells in the population must be capable of reacting to the actual level of the signal in the environment -- in other words, they must be able to perceive the signal and increase their production. The second prerequisite is that synthesis and secretion of the signal reduce the fitness of producer cells. This would be the case, for instance, if signal production requires the expenditure of energy, which would inevitably reduce the division rate of producer cells."Under these conditions, non-producing cells in the model always grow faster than producers. Since all the bacteria in the population can perceive the signal, non-producers may respond to its presence by becoming producers themselves. Bacteria already engaged in signal production, on the other hand, will not further increase its rate of synthesis. "Bacteria react to an environment that is shaped by themselves. This ecological feedback is what makes it possible for phenotypic heterogeneity to arise in genetically identical populations," says Frey. "Our mathematical analysis demonstrates that, once established, such heterogeneity can stably persist and is robust to perturbations."It has been speculated that such heterogeneous production of signaling molecules could be advantageous for the whole population because it allows for a division of labor between signal producers and non-producers, or because the creation of phenotypic diversification provides greater evolutionary flexibility and enables populations to adapt more rapidly to environmental change. However, an understanding of the biological functions of phenotypic heterogeneity in such systems will require dedicated experimental studies, say the authors of the new paper.
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Genetically Modified
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July 20, 2017
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https://www.sciencedaily.com/releases/2017/07/170720142236.htm
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Gene drives likely to be foiled by rapid rise of resistance
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A study in fruit flies suggests that existing approaches to gene drives using CRISPR/Cas9, which aim to spread new genes within a natural population, will be derailed by the development of mutations that give resistance to the drive. Jackson Champer, Philipp W. Messer, and colleagues at Cornell University in Ithaca, New York report these findings July 20, 2017 in
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Gene drives offer tremendous hope for preventing the spread of mosquito-borne diseases and controlling invasive species. Newly developed approaches that use CRISPR/Cas9 gene editing technology can generate offspring that carry copies of the altered gene on both chromosomes -- a phenomenon called super-Mendelian inheritance that, in theory, should quickly convert an entire population. This process, however, can also create resistant genetic sequences and organisms that cannot be converted. In the current study, researchers tested two different CRISPR gene drive constructs in the model fruit fly, The study demonstrates that the evolution of resistance will likely be a severe roadblock for existing CRISPR gene drive approaches, which must be addressed before scientists could successfully employ them in the wild. In the coming years, research groups have planned gene drives in mice on islands off the coast of Massachusetts to prevent the spread of Lyme disease, and in tree snakes in Guam to control these invasive species. New gene drive approaches will be necessary to overcome the challenge posed by resistance, especially in genetically diverse, natural populations.
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Genetically Modified
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July 20, 2017
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https://www.sciencedaily.com/releases/2017/07/170720095111.htm
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A super-algae to save our seas? Genetic engineering species to save corals
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Solutions to climate change, and particularly its effects on the ocean, are needed now more than ever. Coral bleaching caused by climate change is a huge threat to coral reefs. Recent extreme bleaching events have already killed corals worldwide and permanent destruction of reefs is projected within the century if immediate action is not taken. However, genetically engineering a group of microalgae found in corals may enhance their stress tolerance to ocean warming and save coral reefs.
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Coral reefs are our most diverse marine habitat. They provide over US$30 billion to the world economy every year and directly support over 500 million people. However, they are vulnerable with climate change impact models predicting that most of our coral reefs will be eradicated within this century if we do not act immediately to protect them.Dr Rachel Levin from The University of New South Wales, Australia and her international team of researchers may have found a solution to reduce coral bleaching by genetically engineering the microalgae found in corals, enhancing their stress tolerance to ocean warming.These microalgae are called Coral bleaching is caused by changes in ocean temperatures which harm Different species of "Very little is known about The researchers have now highlighted key "However, Dr Levin does warn that this is no easy miracle cure, "If lab experiments successfully show that genetically engineered In order to progress, other researchers will need to contribute to this research to advance the information currently available, "We have developed the first, tailored genetic engineering framework to be applied to
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Genetically Modified
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July 10, 2017
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https://www.sciencedaily.com/releases/2017/07/170710160954.htm
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Natural plant compound may reduce mental effects of aging, more evidence shows
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Salk scientists have found further evidence that a natural compound in strawberries reduces cognitive deficits and inflammation associated with aging in mice. The work, which appeared in the
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"Companies have put fisetin into various health products but there hasn't been enough serious testing of the compound," says Pamela Maher, a senior staff scientist in Salk's Cellular Neurobiology Laboratory and senior author of the paper. "Based on our ongoing work, we think fisetin might be helpful as a preventative for many age-associated neurodegenerative diseases, not just Alzheimer's, and we'd like to encourage more rigorous study of it."Maher, who works in the lab of David Schubert, the head of Salk's Cellular Neurobiology Lab, has been studying fisetin for over a decade. Previous research by the lab found that fisetin reduced memory loss related to Alzheimer's in mice genetically modified to develop the disease. But that study focused on genetic (familial) AD, which accounts for only 1 to 3 percent of cases. By far the bigger risk factor for developing what is termed sporadic AD, as well as other neurodegenerative disorders, is simply age. For the current inquiry, Maher turned to a strain of laboratory mice that age prematurely to better study sporadic AD. By 10 months of age, these mice typically show signs of physical and cognitive decline not seen in normal mice until two years of age.The Salk team fed the 3-month-old prematurely aging mice a daily dose of fisetin with their food for 7 months. Another group of the prematurely aging mice was fed the same food without fisetin. During the study period, mice took various activity and memory tests. The team also examined levels of specific proteins in the mice related to brain function, responses to stress and inflammation."At 10 months, the differences between these two groups were striking," says Maher. Mice not treated with fisetin had difficulties with all the cognitive tests as well as elevated markers of stress and inflammation. Brain cells called astrocytes and microglia, which are normally anti-inflammatory, were now driving rampant inflammation. Mice treated with fisetin, on the other hand, were not noticeably different in behavior, cognitive ability or inflammatory markers at 10 months than a group of untreated 3-month-old mice with the same condition. Additionally, the team found no evidence of acute toxicity in the fisetin-treated mice, even at high doses of the compound."Mice are not people, of course," says Maher, "But there are enough similarities that we think fisetin warrants a closer look, not only for potentially treating sporadic AD but also for reducing some of the cognitive effects associated with aging, generally."Next, Maher hopes to partner with another group or company in order to conduct clinical trials of fisetin with human subjects.
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Genetically Modified
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July 6, 2017
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https://www.sciencedaily.com/releases/2017/07/170706114544.htm
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Humpback whales: Calving ground loyalty drives population differences, study finds
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Scientists conducting the first circum-global assessment of mitochondrial DNA variation in the Southern Hemisphere's humpback whales (Megaptera novaeangliae) have found that whales faithfully returning to calving grounds year after year play a major role in how populations form, according to WCS (Wildlife Conservation Society), the American Museum of Natural History, and a number of other contributing organizations.
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The research results build on previous regional studies of genetic diversity and will help scientists to better understand how humpback whale populations evolve over time and how to best advise international management authorities.The paper titled "First Circumpolar Assessment of Southern Hemisphere Humpback Whale Mitochondrial Genetic Variation at Multiple Scales and Implications for Management" now appears in the online version of "Exploring the relationships of humpback whales around the Southern Hemisphere has been a massive undertaking requiring years of work and collaboration by experts from more than a dozen countries," said Dr. Howard Rosenbaum, Director of WCS's Ocean Giants Program and lead author on the study. "Our findings give us insights into how fidelity to breeding and feeding destinations persist over many generations, resulting in differences between whale populations, and why some populations are more genetically differentiated from the rest. From these efforts, we are in better positions to inform actions and policies that will help protect Southern Hemisphere humpback whales across their range, as well as in the Arabian Sea."In the largest study of its kind to date, researchers used mitochondrial DNA microsatellites from skin samples gathered from more than 3,000 individual humpback whales across the Southern Hemisphere and the Arabian Sea to examine how whale populations are related to one another, a question that is difficult to answer with direct observations of whales in their oceanic environment. Overall, the study's data from mitochondrial DNA -- different from nuclear DNA in that it helps scientists trace maternal lineages -- reveal that population structure in humpback whales is largely driven by female whales that return annually to the same breeding grounds and by the early experience of calves that accompany their mothers on their first round-trip migration to the feeding grounds. The persistence of return to these migratory destinations over generations, is known as 'maternally directed site fidelity'.The occasional genetic interchange between populations also seemed to correlate with feeding grounds with high densities of krill, places where whales from different populations are likely to move vast distances and come into contact with other populations. The study also identified specific populations -- those inhabiting the eastern South Pacific off of Colombia and a non-migratory population in the Arabian Sea -- as more genetically distinct and isolated from other nearby populations and perhaps in need of additional management and conservation consideration."Our increased understanding of how whale populations are structured can help governments and inter-governmental organizations like the International Whaling Commission improve management decisions in the future," said Dr. C. Scott Baker of Oregon State University's Marine Mammal Institute and a member of the South Pacific Whale Research Consortium that contributed to the study.The humpback whale reaches a body length of 50 feet and, as a largely coastal species, is popular with whale watch operations around the world. Before receiving international protection in 1966, humpback whales were targeted by commercial whaling vessels that nearly drove the species into extinction. This included more than 45,000 humpback whales taken illegally by the Soviet Union after World War II. Current threats to humpback whales include ship strikes, underwater noise, pollution, and entanglement in fishing gear.These threats are particularly pertinent to humpback whales in the Arabian Sea, a genetically isolated population numbering fewer than 100 animals and currently listed on the IUCN's Red List of Threatened Species as "Endangered." WCS's research is done in collaboration with a number of regional and local partners in the Arabian Sea working on advocacy and conservation, notably the Environment Society of Oman, among others.
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Genetically Modified
| 2,017 |
July 5, 2017
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https://www.sciencedaily.com/releases/2017/07/170705132903.htm
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Genetics may lie at the heart of crop yield limitation
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You might think that plants grow according to how much nutrition, water and sunlight they are exposed to, but new research by Dr Nick Pullen and a team from the John Innes Centre, UK shows that the plant's own genetics may be the real limiting factor.
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"This could have potentially big implications for the agricultural industry," says Dr Pullen, "Our model plant is in the same family as cabbages, so it's easy to imagine creating giant cabbages or growing them to the desired market size faster than at present."It was previously assumed that plant growth was generally resource-limited, meaning that plants would only grow as large and fast as they could photosynthesise. However, Dr Pullen and his team present evidence that plant growth is actually "sink-limited," meaning that genetic regulation and cell division rates have a much bigger role in controlling plant growth than previously thought: "We are proposing that plant growth is not physically limited by Net Primary Productivity (NPP) or the environment, but instead is limited genetically in response to these signals to ensure they do not become limiting."By genetically altering the growth repressors in Arabidopsis, Dr Pullen and his team were able to create mutant strains. They identified the metabolic rates of the different plant strains by measuring rates of photosynthesis and respiration, as well as comparing the size and weight of the plants to monitor differences in physical growth.Dr Pullen and the team also grew the mutant plant strains at different temperatures to see if this changed their results: "When grown at different temperatures we still find a difference in size of our plants between wildtype and the mutants. This suggests our results should be applicable in different climates."The impact of these results is wide-reaching, and Dr Pullen suggests that it may even change how we think about global climate data: "Climate models need to incorporate genetic elements because at present most do not, and their predictions would be much improved with a better understanding of plant carbon demand."
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Genetically Modified
| 2,017 |
July 3, 2017
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https://www.sciencedaily.com/releases/2017/07/170703085614.htm
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Viruses over antibiotics: Determining the 3D structure of phages at atomic resolution closer thanks to new method
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Phages have become a focus of research in the battle against antibiotic resistance. These bacteria-eating viruses have already proven effective in experiments against multidrug-resistant bacteria. However, the atomic structure of these small helpers is unknown. Researchers at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) in Berlin have now succeeded in developing a new method that makes it possible to determine the complex structure in detail, down to the atomic level. Their work is a further development in solid-state NMR and was published in the specialist journals
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The WHO has long declared resistance to antibiotics a global health crisis and published a list of problematic germs, most recently in March, for which new antibiotics are urgently needed. But the search for new antibiotics has proven to be difficult: There has been no significant progress in development for over 40 years. This is why researchers are now more than ever looking for alternative treatments. Phages could constitute such an alternative. They are naturally occurring viruses that attack and consume certain bacteria, which is why they are also called "bacteriophages" (ancient Greek φαγεῖν phageín, "to devour"). Since there are special phages for every bacterium, it appears that they can be deployed more specifically than antibiotics, which always kill "good" bacteria as well. A lot of experiments with bacteriophages have already been carried out in Eastern Europe, and in the U.S. they have been genetically manipulated so they are able to cure infections of multiresistant germs in mice.The atomic structure of the phages is not fully known to date. In the course of current therapy development, however, it would be tremendously useful to know how exactly they operate and what their 3D structure looks like at atomic detail. "Phages are nanomachines that have been optimized by nature over millions of years. They consist of numerous components that are assembled into a complex architecture," explains Professor Dr. Adam Lange (FMP). Lange and his team have now succeeded in reaching a methodological milestone: The researchers have developed solid-state NMR (nuclear magnetic resonance spectroscopy) methods so that they can be used to determine the structure of phages down to the atomic level. Lange estimates that he will need about a year to resolve the complex structure of the phages. "By carrying out this fundamental research, we can make an important contribution to phage therapy."The new method can be applied to other important systems as well. To provide access for laboratories around the world, in addition to the paper in "Bacteriophages are becoming increasingly important as an alternative treatment approach due to the resistance of many pathogenic bacteria strains to antibiotics," Lange concludes. He is one of the leading minds in the field of making protein structures visible with NMR. "Therefore, we will now put our further development of the technology to use and investigate their complex structure as quickly as possible."
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Genetically Modified
| 2,017 |
June 29, 2017
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https://www.sciencedaily.com/releases/2017/06/170629105253.htm
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Variation at a central metabolic gene influences male fruit fly lifespan
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The overexpression of an important gene that regulates energy metabolism can cause a severe shortening of lifespan in male fruit flies but has only a small negative effect on lifespans of female fruit flies, according to new research from North Carolina State University. The findings, which involve metabolic genes and pathways that are important in humans and other animals, shed more light on sex-specific differences between male and female lifespans.
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NC State biologists experimented with either inhibiting or overexpressing the bellwether gene, which gives rise to a protein that helps convert nutrients into metabolic energy. Small variations in regions of that gene that regulate its expression were suspected to be correlated with differences in lifespan based on a previous study, said Robert Anholt, William Neal Reynolds Distinguished Professor of Biological Sciences at NC State and the corresponding author on a paper describing the research, published in In the study, Julia Frankenberg Garcia, a visiting student from the University of Surrey in the UK, and Mary Anna Carbone, a research assistant professor of biological sciences at NC State, suppressed expression of the bellwether gene and found that the gene is required for fruit fly development and viability."Knocking down the expression of this gene is lethal for fruit flies -- male and female," said Anholt, who also directs NC State's W.M. Keck Center for Behavioral Biology.The researchers then examined a number of DNA variants in the protein production-control region of the bellwether gene in cell cultures. Some DNA variants worked better than others and some of those differences were also replicated in vivo -- in living fruit flies.Finally, the researchers overexpressed DNA variants in fruit flies that were genetically identical except for these different DNA variants. They found that one particular DNA variant shortened male fruit fly lifespan by nearly two-thirds. Females with that DNA variant had shorter lifespans, but this effect was much smaller than in males."This is a powerful demonstration of how we can link variation in the genome that controls expression of a central metabolic enzyme to variation in individual lifespan," Anholt said. "There are different gene-gene interactions even though the flies are genetically the same, so that the female genetic background seems to become more protective."Anholt said that the dramatic effect on male lifespan was unexpected."It speaks to the importance of the gene, which is required for development but when overexpressed becomes more lethal for males," Anholt said, "Moreover, the same gene has conserved counterparts in all animals, including people."
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Genetically Modified
| 2,017 |
June 26, 2017
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https://www.sciencedaily.com/releases/2017/06/170626124424.htm
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Novel viral vectors deliver useful cargo to neurons throughout the brain and body
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Viruses have evolved to be highly effective vehicles for delivering genes into cells. Seeking to take advantage of these traits, scientists can reprogram viruses to function as vectors, capable of carrying their genetic cargo of choice into the nuclei of cells in the body. Such vectors have become critical tools for delivering genes to treat disease or to label neurons and their connective fibers with fluorescent colors to map out their locations. Because viral vectors have been stripped of their own genes and, thereby, of their ability to replicate, they are no longer infectious. Therefore, achieving widespread gene delivery with the vectors is challenging. This is especially true for gene delivery to hard to reach organs like the brain, where viral vectors have to make their way past the so-called blood-brain barrier, or to the peripheral nervous system, where neurons are dispersed across the body.
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Now, to enable widespread gene delivery throughout the central and peripheral nervous systems, Caltech researchers have developed two new variants of a vector based on an adeno-associated virus (AAV): one that can efficiently ferry genetic cargo past the blood-brain barrier; and another that is efficiently picked up by peripheral neurons residing outside the brain and spinal cord, such as those that sense pain and regulate heart rate, respiration, and digestion. Both vectors are able to reach their targets following a simple injection into the bloodstream. The vectors are customizable and could potentially be used as part of a gene therapy to treat neurodegenerative disorders that affect the entire central nervous system, such as Huntington's disease, or to help map or modulate neuronal circuits and understand how they change during disease.The work was done in the laboratory of Viviana Gradinaru, assistant professor of biology and biological engineering, Heritage Medical Research Institute Investigator, director of the Center for Molecular and Cellular Neuroscience in the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech, and principal investigator of the Beckman Institute's CLOVER (CLARITY, Optogenetics, and Vector Engineering Research) Center.A paper describing the research appears online in the June 26 issue of "We have now developed a new collection of viruses and tools to study the central and peripheral nervous systems," says Gradinaru. "We are now able to get highly efficient brain-wide delivery with just a low-dose systemic injection, access neurons in difficult-to-reach regions, and precisely label cells with multiple fluorescent colors to study their shapes and connections."Gradinaru and her team modified the external surface of an AAV developed in 2016, engineering the virus's shell, or capsid, to allow it to more efficiently deliver genes to cells in the brain and spinal cord following intravenous injection. They named the new virus AAV-PHP.eB.The team also developed an additional capsid variant they call AAV-PHP.S, which is able to transduce peripheral neurons."Neurons outside of the central nervous system have many functions, from relaying sensory information to controlling organ function, but some of these peripheral neural circuits are not yet well understood," says Ben Deverman, senior research scientist and director of the Beckman Institute's CLOVER Center. "The AAV-PHP.S vector that we developed could help researchers study the activity and function of specific types of neurons within peripheral circuits using genetically-encoded sensors and tools to modulate neuronal firing with light or designer drugs, respectively."The new AAV vectors can also deliver genes that code for colorful fluorescent proteins; such proteins are useful in identifying and labeling cells. In this process, multiple AAVs -- each carrying a distinct color -- are mixed together and injected into the bloodstream. When they reach their target neurons, each neuron receives a unique combination of colors, thereby giving it a visually distinct hue that makes it easier for the researchers to distinguish its fine details from those of its neighbors. Furthermore, the team devised a technique to control the number of neurons labeled -- labeling too many neurons makes it impossible to distinguish individual ones -- that allows researchers to visualize individual neuron shapes and trace their connecting fibers through intact tissues using another technology the Gradinaru laboratory has helped develop, known as tissue clearing."Usually, when researchers want a mouse or other animal model to express fluorescent proteins in certain cells, they need to develop genetically modified animals that can take months to years to make and characterize," says former graduate student and first author Ken Chan (PhD '17). "Now with a single injection, we can label specific cells with a variety of colors within weeks after the injection.""For our new systemic viral vectors -- AAV PHP.S and AAV PHP.eB -- there are many potential uses, from mapping circuits in the periphery and fast screening of gene regulatory elements to genome editing with powerful tools such as CRISPR-Cas9," says Gradinaru. "But perhaps the most exciting implication is that our tools, when paired with appropriate activity modulator genes, could enable non-invasive deep brain modulation for the treatment of neurological diseases such as Parkinson's disease."
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Genetically Modified
| 2,017 |
June 19, 2017
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https://www.sciencedaily.com/releases/2017/06/170619120317.htm
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Unusual soybean coloration sheds a light on gene silencing
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Today's soybeans are typically golden yellow, with a tiny blackish mark where they attach to the pod. In a field of millions of beans, nearly all of them will have this look. Occasionally, however, a bean will turn up half-black, with a saddle pattern similar to a black-eyed pea.
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"The yellow color is derived from a natural process known as gene silencing, in which genes interact to turn off certain traits," explains Lila Vodkin, professor emerita in the Department of Crop Sciences at the University of Illinois. "Scientists make use of this process frequently to design everything from improved crops to medicines, but examples of naturally occurring gene silencing -- also known as RNA interference, or RNAi -- are limited. A better understanding of this process can explain how you can manipulate genes in anything from soybeans to humans."The RNAi pathway was discovered about 20 years ago as a naturally occurring process in a tiny roundworm. The discovery and follow-up work showing its biomedical potential won scientists the Nobel Prize in 2006. In plants, RNAi was discovered in petunias. When breeders tried to transform one gene to cause brighter pinks and purples, they wound up with white flowers instead. The gene for flower color had been silenced."Before they were domesticated, soybeans were black or brown due to the different anthocyanin pigments in the seed coat," says Sarah Jones, a research specialist working with Vodkin on the study. "Breeders got rid of the dark pigments because they can discolor the oil or soybean meal during extraction processes."Vodkin clarifies, "The yellow color was a naturally occurring RNAi mutation that happened spontaneously, probably at the beginning of agriculture, like 10,000 years ago. People saw the yellow beans as different. They picked them up, saved them, and cultivated them. In the germplasm collections of the wild soybean, Glycine sojae, you don't find the yellow color, only darkly pigmented seeds."Previous work from the team showed that yellow soybeans result from a naturally occurring gene silencing process involving two genes. Essentially, one of the genes blocks production of the darker pigment's precursors. But the researchers weren't sure why black pigments sometimes reappear, as in saddle-patterned beans. Now they know.Vodkin and her team searched for beans with unusual pigmentation in the USDA soybean germplasm collection, housed at U of I. The collection contains thousands of specimens, representing much of the genetic diversity in domesticated soybean and its wild relatives."We requested beans with this black saddle pattern," Jones recalls. "We wanted to know if they all get this pattern from the same gene." Some of the samples had been collected as far back as 1945.The team used modern genomic sequencing techniques, quickly sifting through some 56,000 protein-coding genes to identify the one responsible for the pattern. The lead author, Young Cho, made the discovery as a graduate student when he noticed a defect in the Argonaute5 gene. The team looked at additional beans with the saddle and found that the Argonaute5 gene was defective in a slightly different way in each of them."That's how you prove you found the right gene," Vodkin says, "because of these independent mutations happening at different spots right in that same gene."When the Argonaute5 gene is defective, the silencing process -- which normally blocks the dark pigment and results in yellow beans -- can no longer be carried out. The gene defect explains why the dark pigments show up in the saddle beans.Before the team's discovery, there were very few examples of how gene interactions work to achieve silencing in naturally occurring systems. Today, bioengineers use genetic engineering technologies to silence genes to produce a desired outcome, whether it's flower color, disease resistance, improved photosynthesis, or any number of novel applications."The yellow color in soybeans could have been engineered, if it hadn't occurred naturally," Vodkin says, "but it would have cost millions of dollars and every yellow soybean would be a genetically modified organism. Nature engineered it first." She says this study also emphasizes the value of the soybean germplasm collection, which preserves diversity for research and breeding purposes.
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Genetically Modified
| 2,017 |
June 19, 2017
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https://www.sciencedaily.com/releases/2017/06/170619105137.htm
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DNA delivery technology joins battle against drug-resistant bacteria
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Antimicrobial resistance is one of the biggest threats to global health, affecting anyone, at any age, in any country, according to the World Health Organization. Currently, 700,000 deaths each year are attributed to antimicrobial resistance, a figure which could increase to 10 million a year by 2050 save further intervention.
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New breakthrough technology from Tel Aviv University facilitates DNA delivery into drug-resistant bacterial pathogens, enabling their manipulation. The research expands the range of bacteriophages, which are the primary tool for introducing DNA into pathogenic bacteria to neutralize their lethal activity. A single type of bacteriophage can be adapted to a wide range of bacteria, an innovation which will likely accelerate the development of potential drugs based on this principle.Prof. Udi Qimron of the Department of Clinical Microbiology and Immunology at TAU's Sackler Faculty of Medicine led the research team, which also included Dr. Ido Yosef, Dr. Moran Goren, Rea Globus and Shahar Molshanski, all of Prof. Qimron's lab. The study was recently published in For the research, the team genetically engineered bacteriophages to contain the desired DNA rather than their own genome. They also designed combinations of nanoparticles from different bacteriophages, resulting in hybrids that are able to recognize new bacteria, including pathogenic bacteria. The researchers further used directed evolution to select hybrid particles able to transfer DNA with optimal efficiency."DNA manipulation of pathogens includes sensitization to antibiotics, killing of pathogens, disabling pathogens' virulence factors and more," Prof. Qimron said. "We've developed a technology that significantly expands DNA delivery into bacterial pathogens. This may indeed be a milestone, because it opens up many opportunities for DNA manipulations of bacteria that were impossible to accomplish before."This could pave the way to changing the human microbiome -- the combined genetic material of the microorganisms in humans -- by replacing virulent bacteria with a-virulent bacteria and replacing antibiotic-resistant bacteria with antibiotic-sensitive bacteria, as well as changing environmental pathogens," Prof. Qimron continued."We have applied for a patent on this technology and are developing products that would use this technology to deliver DNA into bacterial pathogens, rendering them a-virulent and sensitive to antibiotics," Prof. Qimron said.
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Genetically Modified
| 2,017 |
June 15, 2017
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https://www.sciencedaily.com/releases/2017/06/170615142848.htm
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New genetic technique could help identify potential drug targets for malaria
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Scientists have developed a new technique for investigating the effects of gene deletion at later stages in the life cycle of a parasite that causes malaria in rodents, according to a new study in
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New treatments are needed for malaria because of increasing drug resistance in the single-celled In the new study, the researchers demonstrate their novel technique by focusing on an important metabolic process in Heme synthesis is known to be essential for Rathnapala and colleagues produced The researchers found that FC-deficient parasites were unable to complete their liver development phase. This suggests that disrupting the heme synthesis pathway could be an effective way to target This same novel approach involving fluorescent markers could be adapted for other genes, allowing scientists to identify additional metabolic processes that are essential for "The idea of tagging mutant genes with fluorescent proteins is a simple one but it allowed us to follow mutant parasites throughout the malaria life cycle and dissect their phenotypes in the liver stage, something that hasn't been easy to do for mutations that block mosquito development," the author explain. "Our analysis of heme biosynthesis shows the power of this simple method but It's a technique that can be easily applied to other genes and other malaria parasite species, greatly expanding the scope for investigating this immunologically important stage in the malaria parasite's life cycle."
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Genetically Modified
| 2,017 |
June 13, 2017
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https://www.sciencedaily.com/releases/2017/06/170613145146.htm
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E. coli bacteria's defense secret revealed
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By tagging a cell's proteins with fluorescent beacons, Cornell researchers have found out how E. coli bacteria defend themselves against antibiotics and other poisons. Probably not good news for the bacteria.
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When undesirable molecules show up, the bacterial cell opens a tunnel though its cell wall and "effluxes," or pumps out, the intruders."Dynamic assembly of these tunnels has long been hypothesized," said Peng Chen, professor of chemistry and chemical biology. "Now we see them."The findings could lead to ways to combat antibiotic-resistant bacteria with a "cocktail" of drugs, he suggests: "One is to inhibit the assembly of the tunnel, the next is to kill the bacteria."To study bacteria's defensive process, Chen and colleagues at Cornell selected a strain of E. coli known to pump out copper atoms that would otherwise poison the bacteria. The researchers genetically engineered it, adding to the DNA that codes for a defensive protein an additional DNA sequence that codes for a fluorescent molecule.Under a powerful microscope, they exposed a bacterial cell to an environment containing copper atoms and periodically zapped the cell with an infrared laser to induce fluorescence. Following the blinking lights, they had a "movie" showing where the tagged protein traveled in the cell. They further genetically engineered the various proteins to turn their metal-binding capability on and off, and observed the effects.Their research was reported in the Early Online edition of the The key protein, known as CusB, resides in the periplasm, the space between the inner and outer membranes that make up the bacteria's cell wall. When CusB binds to an intruder -- in this experiment, a copper atom -- that has passed through the porous outer membrane, it changes its shape so that it will attach itself between two related proteins in the inner and outer membranes to form a complex known as CusCBA that acts as a tunnel through the cell wall. The inner protein has a mechanism to grab the intruder and push it through.The tunnel locks the inner and outer membranes together, making the periplasm less flexible and interfering with its normal functions. The ability to assemble the tunnel only when needed, rather than having it permanently in place, gives the cell an advantage, the researchers point out.This mechanism for defending against toxic metals may also explain how bacteria develop resistance to antibiotics, by mutating their defensive proteins to recognize them. Similar mechanisms may be found in other species of bacteria, the researchers suggested.
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Genetically Modified
| 2,017 |
June 7, 2017
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https://www.sciencedaily.com/releases/2017/06/170607123744.htm
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Highly safe biocontainment strategy hopes to encourage greater use of GMOs
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Use of genetically modified organisms (GMOs) -- microorganisms not found in the natural world but developed in labs for their beneficial characteristics -- is a contentious issue.
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For while GMOs could greatly improve society in numerous ways -- e.g. attacking diseased cells, digesting pollution, or increasing food production -- their use is heavily restricted by decades-old legislation, for fear of what might happen should they escape into the environment.For researchers, aware of their potential, it is important to develop safety strategies to convince legislators they are safe for release.For this reason Hiroshima University's Professor Ryuichi Hirota and Professor Akio Kuroda, have developed an extra safe phosphite-based biocontainment strategy.Biocontainment strategies -- methods used to prevent GMO escape or proliferation beyond their required use, typically employ one of two forms.One is "suicide switch" where released GMOs die off independently after a given time. The other is "nutrient requirement," where GMOs are designed to expire on removal of a nutrient source.The control method for the new genetically modified It relies on the fact that all living things require phosphorus for a vast array of life-determining processes including energy storage, DNA production, and cell signal-transduction. The overwhelming majority of bacteria, source phosphorus from the naturally occurring nutrient phosphate.However, bacteria are renowned for their ability to obtain energy from seemingly implausible sources and the researchers at HU found one type, Ralstonia sp. Strain 4506, capable of utilizing non-naturally occurring phosphite instead -- throwing up exciting possibilities.As Phosphite, a waste by-product from the metal plating industry, does not occur in the natural world, scientists can easily control its availability and determine potential GMO proliferation.Strain 4506's phosphite-digesting enzyme was thus isolated and introduced into But while this modified As When the resulting GMO was tested the results were outstanding. It proliferated in a phosphite medium, and didn't grow at all when exposed only to phosphate.Further, when thriving populations were later deprived of their phosphite-hit, their numbers tumbled over a two week period to zero -- thus fulfilling the criteria for "nutrition requirement" biocontainment.However, what the scientists discovered next astounded them. Even when this new GMO was successfully and continuously cultured on phosphite, its population nevertheless still began plummeting after two weeks.Baffled, the HU researchers are investigating but there is a possibility that this strategy possesses "suicide switch" characteristics on top of "nutrient requirement."Whatever the reason, an extremely safe and practical biocontainment strategy has been born. Requiring just nine simple gene edits, in naturally occurring organisms, and based on phosphite -- a readily available industrial waste product; it is extremely cost and time effective. Additionally, its simplicity means it can be adapted for other microorganisms, making it highly versatile.These traits contrast with previous biocontainment strategies involving synthetic organisms and energy sources, requiring hundreds of gene edits, awful lots of money and time, and which are so specialized as to make them impractical.It is hoped this new strategy will grab the attention of relevant government agencies, and convince them to bring 1980s laws in line with 21st Century advancements. We can then get GMOs safely out of the lab for the betterment of society!
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Genetically Modified
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June 5, 2017
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https://www.sciencedaily.com/releases/2017/06/170605121323.htm
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Bio-based p-xylene oxidation into terephthalic acid by engineered E. coli
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KAIST researchers have established an efficient biocatalytic system to produce terephthalic acid (TPA) from p-xylene (pX). It will allow this industrially important bulk chemical to be made available in a more environmentally-friendly manner.
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The research team developed metabolically engineered The research team utilized a metabolic engineering and synthetic biology approach to develop a recombinant microorganism that can oxidize pX into TPA using microbial fermentation. TPA is a globally important chemical commodity for manufacturing PET. It can be applied to manufacture plastic bottles, clothing fibers, films, and many other products. Currently, TPA is produced from pX oxidation through an industrially well-known chemical process (with a typical TPA yield of over 95 mol%), which shows, however, such drawbacks as intensive energy requirements at high temperatures and pressure, usage of heavy metal catalysts, and the unavoidable byproduct formation of 4-carboxybenzaldehyde.The research team designed and constructed a synthetic metabolic pathway by incorporating the upper xylene degradation pathway of Using this best-performing strain, the team designed an elegant two-phase (aqueous/organic) fermentation system for TPA production on a larger scale, where pX was supplied in the organic phase. Through a number of optimization steps, the team ultimately achieved production of 13.3 g TPA from 8.8 g pX, which represented an extraordinary yield of 97 mol%.The team has developed a microbial biotechnology application which is reportedly the first successful example of the bio-based production of TPA from pX by the microbial fermentation of engineered Professor Lee said, "We presented promising biotechnology for producing large amounts of the commodity chemical TPA, which is used for PET manufacturing, through metabolically engineered gut bacterium. Our research is meaningful in that it demonstrates the feasibility of the biotechnological production of bulk chemicals, and if reproducible when up-scaled, it will represent a breakthrough in hydrocarbon bioconversions."
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Genetically Modified
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