Hall A.B.,Virginia Polytechnic Institute and State University |
Hall A.B.,Fralin Life Science Institute |
Basu S.,Fralin Life Science Institute |
Jiang X.,Virginia Polytechnic Institute and State University |
And 16 more authors.
Science | Year: 2015
Sex determination in the mosquito Aedes aegypti is governed by a dominant male-determining factor (M factor) located within a Y chromosome-like region called the M locus. Here, we show that an M-locus gene, Nix, functions as an M factor in A. aegypti. Nix exhibits persistent M linkage and early embryonic expression, two characteristics required of an M factor. Nix knockout with clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 resulted in largely feminized genetic males and the production of female isoforms of two key regulators of sexual differentiation: doublesex and fruitless. Ectopic expression of Nix resulted in genetic females with nearly complete male genitalia. Thus, Nix is both required and sufficient to initiate male development. This study provides a foundation for mosquito control strategies that convert female mosquitoes into harmless males.
News Article | March 28, 2016
The findings, published in the Proceedings of the National Academy of Sciences today (Monday, March 28) will inform a variety of genetically based mosquito control strategies that focus on creating more males than females. Male mosquitoes do not bite and are harmless to humans, while female mosquitoes bite humans to get the blood they need for egg production. "Thirteen years after the publication of a draft genome of the Anopheles gambiae mosquito, we've finally characterized its Y chromosome," said co-author Zhijian Jake Tu, a professor of biochemistry in the College of Agriculture and Life Sciences and a Fralin Life Science Institute affiliate. "This is one of the last pieces of the puzzle. Having the Y will help us figure out the genetic basis of male biology in future studies." The new information about the Y chromosome will facilitate efforts to reduce female mosquitoes or create sterile males—strategies of interest to research teams across the world. "The Y chromosome had previously not been characterized because it mostly consists of repetitive DNA sequences that stump the algorithms used by computers to assemble the mosquito's entire genetic make-up", said co-author Brantley Hall of Christiansburg, Va., a doctoral student in the genetics, bioinformatics and computational biology program. "We were able to get around this obstacle (at least partially) by using a new long single-molecule sequencing technology, a new bioinformatics algorithm specifically designed to identify Y sequences, and physical mapping of DNA directly to the Y chromosome," said co-author Igor Sharakhov, an associate professor of entomology in the College of Agriculture and Life Sciences and a Fralin Life Science Institute affiliate. "Our study provides a long-awaited foundation for studying mosquito Y chromosome biology and evolution." "Our combined efforts have resulted in the most extensive characterization of Y chromosome to date in additional malaria vectors as well, which will help identify targeted vector control approaches for different species," said co-author Atashi Sharma, a doctoral student in the department of entomology in the College of Agriculture and Life Sciences. The research was in collaboration with Nora Besansky, the Rev. John Cardinal O'Hara C.S.C. professor of biological sciences at the University of Notre Dame. Three graduate students at Virginia Tech were involved in the study, with Brantley Hall and Atashi Sharma being co-first authors on the paper. Xiaofang Jiang, a graduate student in the genetics, bioinformatics, and computational biology and biochemistry, Vladimir Timoshevskiy, a research associate, and Maria Sharakhova, an assistant professor of entomology in the College of Agriculture and Life Sciences, from Virginia Tech also participated in the study. Philippos-Aris Papathanos of the University of Perugia and Changde Cheng of the University of Norte Dame are also co-first authors. Malaria causes as many as 907,000 deaths each year, mostly among children in sub-Saharan Africa. Anopheles mosquitoes, which bite mainly between dusk and dawn, transmit human malaria by spreading Plasmodium parasites that multiply in the human liver and infect red blood cells. Explore further: Mosquito genetics may offer clues to malaria control More information: Radical remodeling of the Y chromosome in a recent radiation of malaria mosquitoes, Proceedings of the National Academy of Sciences, www.pnas.org/cgi/doi/10.1073/pnas.1525164113
News Article | September 23, 2016
Researchers with the Virginia Tech Center for Drug Discovery have identified a compound that blocks the growth of a fungus that causes deadly lung infections and allergic reactions in people with compromised immune systems. The research team targeted the switch that allows the fungus Aspergillus fumigatus to survive in iron-deficient conditions like the human body. Specifically, they targeted an enzyme known as SidA, which is essential for the synthesis of molecules called siderophores that are made during infection to steal iron from human proteins. Furthermore, by performing high-throughput screening in the center’s Drug Discovery Screening Laboratory, they found a compound called Celastrol that blocks the growth of iron-producing organelles in the fungus. The results were published in the journal ACS Chemical Biology. “This project shows what an asset the screening lab is to the community,” said Pablo Sobrado, a professor of biochemistry in the College of Agriculture and Life Sciences and director of the screening laboratory. “Without the robots and chemical libraries available at the screening lab, this work would not have been possible. We are very fortunate at Virginia Tech to have this facility.” Aspergillus fumigatus is common and is typically found in soil and decaying organic matter. Most people are exposed to it daily with little consequence, but it can cause lung damage in people with compromised immune systems, such as organ transplant recipients and people with AIDS or leukemia. The mortality rate of this population, when exposed to the fungus, is more than 50 percent, according to the authors. "Growing antibiotic resistance is demanding the development of target-directed therapies," said Julia S. Martin del Campo, a postdoctoral research scientist in Sobrado's lab. "This approach requires the discovery of enzyme inhibitors that block essential pathogen pathways. The discovery of Celastrol as a SidA inhibitor represents the first building block in the development of drugs against A. fumigatus and related pathogens.” The Virginia Tech Center for Drug Discovery was established in 2012 and is an interdisciplinary group committed to continuing the growth and advancing the stature of the existing drug discovery and development programs at Virginia Tech. The center is housed in the College of Science, with support from the College of Science, the Fralin Life Science Institute, the Institute for Critical Technology and Applied Science, and the College of Agriculture and Life Sciences.
News Article | January 28, 2016
Millions of dollars have been spent on insecticides to kill the bugs that have wreaked havoc on everything from hotels in New York City to homes in Los Angeles. But this is the first study to show that overuse of certain insecticides has led to an increased resistance to the compounds, making them much less effective than advertised. "While we all want a powerful tool to fight bed bug infestations, what we are using as a chemical intervention is not working as effectively it was designed and, in turn, people are spending a lot of money on products that aren't working," said Troy Anderson, an assistant professor of entomology in the Virginia Tech College of Agriculture and Life Sciences. Anderson and Alvaro Romero, an assistant professor of entomology at New Mexico State University, published their findings in the Journal of Medical Entomology on Thursday. The two examined the class of insecticides called neonicotinoids, or neonics, which is often paired with pyrethroids in commercial applications to treat bedbugs. "Companies need to be vigilant for hints of declining performance of products that contain neonicotinoids," Romero said. "For example, bedbugs persisting on previously treated surfaces might be an indication of resistance." The researchers conducted their study by comparing bedbugs from homes in Cincinnati and Michigan that had been exposed to neonics with a colony that a researcher has kept isolated since before the insecticide was used. For the last 30 years, the colony has been in an isolated lab run by Harold Harlan with the Armed Forced Pest Management Board. They also examined a pyrethroid-resistant population from New Jersey that had not been exposed to neonics since they were collected in 2008. The bedbugs from Harlan's lab that never have been exposed to neonics died when they were exposed to a very small amount of the insecticide. The New Jersey bedbugs fared slightly better, showing moderate resistance to four different types of neonics. But the bedbugs from Michigan and Cincinnati, which were collected after combinations of insecticides were introduced to the U.S., had much higher levels of resistance to neonics. It only took 0.3 nanograms of a substance called acetamiprid to kill 50 percent of the nonresistant bedbugs from Harlan's lab—but it took more than 10,000 nanograms to kill 50 percent of the Michigan and Cincinnati bedbugs. Just 2.3 nanograms of another substance called imidacloprid was enough to kill 50 percent of Harlan's bedbugs, but it took 1,064 nanograms to kill the Michigan bedbugs and 365 nanograms to kill the Cincinnati bedbugs. Compared with the Harlan control group, the Michigan bedbugs were 462 times more resistant to imidacloprid, 198 times more resistant to dinotefuran, 546 times more resistant to thiamethoxam, and 33,333 times more resistant to acetamiprid. The Cincinnati bedbugs were 163 times more resistant to imidacloprid, 226 times more resistant to thiamethoxam, 358 times more resistant to dinotefuran, and 33,333 times more resistant to acetamiprid. The researchers believe that the detection of neonicotinoid resistance in the New Jersey bedbugs, which were collected before the widespread use of neonics, could be due to pre-existing resistance mechanisms. When exposed to insecticides, bedbugs produce "detoxifying enzymes" to counter them, and the researchers found that the levels of detoxifying enzymes in the New Jersey bedbugs were higher than those of the susceptible Harlan population. "Unfortunately, the insecticides we were hoping would help solve some of our bed bug problems are no longer as effective as they used to be, so we need to reevaluate some of our strategies for fighting them," said Anderson, who is also a researcher at the Fralin Life Science Institute. "If resistance is detected, products with different modes of action need to be considered, along with the use of non-chemical methods," said Romero. More information: "High Levels of Resistance in the Common Bed Bug, Cimex lectularius (Hemiptera: Cimicidae), to Neonicotinoid Insecticides," jme.oxfordjournals.org/lookup/doi/10.1093/jme/tjv253
News Article | December 20, 2016
The soil beneath our feet is not as biologically diverse as scientists previously thought, according to a research team that includes a Virginia Tech soil microbial ecologist The soil beneath our feet is not as biologically diverse as scientists previously thought, according to a research team that includes a Virginia Tech soil microbial ecologist. Leftover DNA from dead organisms -- known as "relic DNA" -- has historically thrown a wrench into estimates, causing scientists to overestimate microbial diversity by as much as 55 percent. Understanding microbial diversity in soil is crucial for understanding how environmental processes like atmospheric nitrogen fixation and climate change occur. But a team that includes Michael Strickland, an assistant professor of biological sciences in the College of Science, used a high throughput sequencing technique to determine the exact make-up of 31 soil samples from varying climates and ecosystems. The results were published in Nature Microbiology this week. "When we started to realize that our numbers could be off, we knew we had to find a way to take a closer look at how many species are actually there," said Strickland, who is also affiliated with the university's Global Change Center and the Fralin Life Science Institute. Information about populations of microbes in soil is important because these organisms play critical roles in the terrestrial ecosystem and they help maintain soil fertility. But linking the activities of microbes to soil processes is difficult. Scientists need to measure living microbes -- a challenging task because DNA from dead microbes can persist in soil for years, obscuring the analysis of microbial diversity. "This research suggests that a significant proportion of the microorganisms detected in soil using DNA based techniques are no longer living," said Ember Morrissey, an assistant professor of plant and soil sciences at West Virginia University who was not involved in the research project. "As a consequence we may need to use tools that distinguish the genetic material of living cells from the relic DNA of dead microbes in order to understand the influence of microbial 'species' on important ecosystem processes." Paul Carini, a microbial ecophysiologist at the University of Colorado Boulder and first author of the paper, used PMA, a photoreactive dye that binds to relic DNA but does not adhere well to living cells, to distinguish viable cells from DNA debris in soil. "Accounting for relic DNA in our analyses will help us understand the important ebb and flow of the soil microbiome and help us better understand how microbes help regulate soil fertility and make earth habitable in the face of a changing climate," said Carini. Although soil microbial communities were found to be less diverse than previously thought, they are still pretty diverse, according to Strickland. In one gram of soil, thousands of species of microbes live, causing Strickland to deem soil as "the poor man's rainforest."
News Article | October 26, 2015
This glue—created when glycoproteins are secreted from a spider's abdomen and interact with the atmosphere—has been studied for the past 12 years by Brent Opell, a professor of biological sciences in the College of Science and a Fralin Life Science Institute affiliate. Material scientists are interested in mimicking this glue—nature's great adhesive—for human products, and rely on biologists to determine factors involved in its creation, as well as its capabilities and limitations. Opell's research team, which included Sarah Stellwagen, a 2015 biological sciences doctoral graduate, and Mary Clouse of Fairfax Station, Virginia, a senior majoring in biological sciences, recently determined that ultraviolet rays, specifically UVB rays, are an important environmental factor in the performance of spider glue. They tested the webs of five local spider species—three that catch prey in broad daylight, and two that hunt at night or in deep forest shade shaded areas. They found that the webs of sun-soaked spiders were far more resistant to UVB rays than the webs of those that hunt in the dark or shade, perhaps indicating an important adaptive trait.The results were published recently in the Journal of Experimental Biology and could inform efforts to develop new adhesives. "Our study adds UVB irradiation to the list of factors known to affect the performance of spider glycoprotein glue, which includes humidity, temperature, and strain rate," Opell said. "It is important to more fully understand these effects as material science moves toward producing environmentally non-toxic and energy conservative adhesives inspired by spider thread glycoprotein." "The work by Opell's research team provides insight on a novel approach used by spiders to withstand UVB light," said Ali Dhinojwala, H.A. Morton Professor in Polymer Science at the University of Akron. "Currently, we add UV stabilizers to prevent degradation of polymers that are exposed to UVB light. Inspired by this study we can learn from the chemistry of spider glue to design new molecules to improve resistance to UVB light." Explore further: Spider web glue spins society toward new biobased adhesives More information: S. D. Stellwagen et al. The impact of UVB radiation on the glycoprotein glue of orb-weaving spider capture thread, Journal of Experimental Biology (2015). DOI: 10.1242/jeb.123067
News Article | October 11, 2016
A popular antibiotic called rifampicin, used to treat tuberculosis, leprosy, and Legionnaire's disease, is becoming less effective as the bacteria that cause the diseases develop more resistance. One of the mechanisms leading to rifampicin's resistance is the action of the enzyme Rifampicin monooxygenase. Pablo Sobrado, a professor of biochemistry in the College of Agriculture and Life Sciences, and his team used a special technique called X-ray crystallography to describe the structure of this enzyme. They also reported the biochemical studies that allow them to determine the mechanisms by which the enzyme deactivates this important antibiotic. The results were published in the Journal of Biological Chemistry and PLOS One, respectively. "In collaboration with Professor Jack Tanner at the University of Missouri and his postdoc, Dr. Li-Kai Liu, we have solved the structure of the enzyme bound to the antibiotic," said Sobrado, who is affiliated with the Fralin Life Science Institute and the Virginia Tech Center for Drug Discovery. "The work by Heba, a visiting graduate student from Egypt, has provided detailed information about the mechanism of action and about the family of enzymes that this enzyme belongs to. This is all-important for drug design." Heba Adbelwahab, of Damietta, Egypt, a graduate student in Sobrado's lab, was a key player in the research and first author of the PLOS One paper. "Antibiotic resistance is one of the major problems in modern medicine," said Adbelwahab. "Our studies have shown how this enzyme deactivates rifampicin. We now have a blueprint to inhibit this enzyme and prevent antibiotic resistance." Rifampicin, also known as Rifampin, has been used to treat bacterial infections for more than 40 years. It works by preventing the bacteria from making RNA, a step necessary for growth. The enzyme, Rifampicin monooxygenase, is a flavoenzyme -- a family of enzymes that catalyze chemical reactions that are essential for microbial survival. These latest findings represent the first detailed biochemical characterization of a flavoenzyme involved in antibiotic resistance, according to the authors. Tuberculosis, leprosy, and Legionnaire's disease are infections caused by different species of bacteria. While treatable, the diseases pose a threat to children, the elderly, people in developing countries without access to adequate health care, and people with compromised immune systems.
News Article | June 11, 2016
Evolution is part of survival. This rings true for common garter snakes that were found to have evolved to survive on toxic newts. Researchers led by Joel McGlothlin, a Virginia Tech Global Change Center affiliate, have found that several snake species like the common garter snakes are able to prey on poisonous animals such as the rough-skinned newts thanks to a hundred million years of evolution. The snakes' ability to fight toxins produced by the amphibians is due to only one alteration in the gene, which created a domino effect — one genetic change triggers a change in another. Over a period of time, the amino acids acting on three sodium channels present in the snakes' muscles and nerves evolved, allowing some of the snakes to counter the toxicity of the newts. However, the researchers also found that the evolution of resistant muscles can only be possible in species that have the resistant nerves, which evolved about 40 million years before. "Garter snakes and newts are locked in a coevolutionary arms race where as the newts become more toxic, the snakes become more resistant," said McGlothlin, who is also an affiliate of Fralin Life Science Institute and a biological sciences assistant professor at the Virginia Tech College of Science. "However, without the leg-up provided by those resistant nerves, snakes wouldn't have been able to withstand enough toxin to get this whole process started." For their study, the researchers conducted gene sequencing of three sodium channels in 82 species, including 78 snakes, two lizards, one turtle and one bird. Gene mapping revealed when the evolutionary gene started to appear. The researchers noted that the snakes gain more toxin resistance as time passed, with gene changes following a specific order — resistant nerves developing prior to the toxin resistant muscle. "The two nerve channels outside the brain, however, have both evolved resistance to the toxin, and they've done so independently. When we compared the DNA sequences to a closely related lizard, there were changes unique to the snakes that should provide resistance to the toxin," said McGlothlin. They also noted that some species of the birds can prey on toxic newts and still survive. To further understand the pattern, the researchers are planning to study how the birds developed the same resistance. McGlothlin said their study is an important look at the complexity of gene adaptation. The National Science Foundation-funded study will be published in Current Biology on June 20. © 2016 Tech Times, All rights reserved. Do not reproduce without permission.
News Article | September 22, 2016
Virginia Tech researchers have found a gene that can reduce female mosquitoes over many generations. Males are preferred because they do not bite. Female mosquitoes bite to get blood for egg production and are the prime carriers of the pathogens that cause malaria, Zika, and dengue fever. In this case, Zhijian "Jake" Tu and colleagues found that placing a particular Y chromosome gene on the autosomes of Anopheles stephensi mosquitoes—a species responsible for transmitting malaria—killed off 100 percent of all female embryos that inherited this gene. The extra copy of this gene, which the researchers call Guy1, is passed on to both sexes but only males survive. Furthermore, these male mosquitoes do not appear to have any detectable reproductive disadvantages in the laboratory. The findings were published Sept. 20 in the journal eLife. "The Guy1 protein is a strong candidate of the male determining factor in Anopheles stephensi," said Tu, a professor of biochemistry in the College of Agriculture and Life Sciences and a member of the Fralin Life Science Institute Vector-borne Disease Research Group. The Guy1 gene is not related to Nix, a male determining factor recently discovered in the Aedes aegypti mosquito by Tu's lab and collaborators. "The extra copy of the Guy1 gene is only passed down to half of the progeny, leaving some females among the mosquitoes that did not inherit the gene in the next generation," said Frank Criscione, who is the first author of the paper and worked on the project when he was a graduate student in the Tu laboratory. In order to produce all male offspring, all progeny needs to inherit this extra copy of Guy1. This is one of the group's future objectives and can potentially be achieved by using genome-editing
Cheng Z.,Fralin Life Science Institute |
Almeida F.A.,Fralin Life Science Institute
Cell Cycle | Year: 2014
The growing epidemic of type 2 diabetes mellitus (T2DM) and obesity is largely attributed to the current lifestyle of over-consumption and physical inactivity. As the primary platform controlling metabolic and energy homeostasis, mitochondria show aberrant changes in T2DM and obese subjects. While the underlying mechanism is under extensive investigation, epigenetic regulation is now emerging to play an important role in mitochondrial biogenesis, function, and dynamics. In line with lifestyle modifications preventing mitochondrial alterations and metabolic disorders, exercise has been shown to change DNA methylation of the promoter of PGC1α to favor gene expression responsible for mitochondrial biogenesis and function. In this article we discuss the epigenetic mechanism of mitochondrial alteration in T2DM and obesity, and the effects of lifestyle on epigenetic regulation. Future studies designed to further explore and integrate the epigenetic mechanisms with lifestyle modification may lead to interdisciplinary interventions and novel preventive options for mitochondrial alteration and metabolic disorders. © 2014 Landes Bioscience.