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  • Duke University Department of Molecular Genetics & Microbiology
    TB in humans The wildtype normal fish has optimal inflammation and is able to control infection well In contrast its siblings have been altered to produce either low or high levels of key mediators of inflammation Producing too little or too much of these mediators results in difficult keeping the infection under control After they understood the biological basis of susceptibility to infection in the zebrafish the researchers turned to the same gene in humans They identified a sequence of the gene that led to higher activity and increased inflammation They then collaborated with other researchers at the University of Washington including Dr Mary Claire King and researchers in Vietnam and the U K including Dr Guy Thwaites to study the gene among patients in Vietnam with TB They discovered that patients carrying one copy of the high activity sequence of the gene and one copy of the low activity sequence were relatively protected from TB meningitis a particularly deadly form of TB Surprisingly people with two copies of the high activity sequence of the gene fared just as poorly as people with two copies of the low activity sequence This heterozygous advantage or Goldilocks effect is an unusual finding in human genetics King commented Throughout human history people with both forms of the LTA4H gene have probably been more likely to survive when exposed to TB than people with only one form of the LTA4H gene This advantage may have led to both forms of the gene persisting in human populations Selection by infectious diseases has had an enormous impact on the evolution of our species This surprising finding the researchers noted implicated both insufficient and overly abundant inflammation as different ways TB could take hold in the body By analyzing clinical data from patients in Vietnam with a particularly severe form of TB called TB meningitis the researchers found that anti inflammatory therapy only benefited patients with the gene sequence that corresponds to excess inflammation The patients with the insufficient inflammation gene sequence derived no benefit from what has been adopted as a standard therapy for TB meningitis Given the clinical and therapeutic implications of these findings the researchers sought the underlying molecular mechanisms for both extremes For this they turned back to the zebrafish In collaboration with Dr Charles Serhan of Harvard University they showed that one gene variant weakened inflammation through the overproduction of substances called lipoxins Hyperinflammation results from a gene variant that leads to an excess of leukotriene B4 Either can interfere with the overall levels of tumor necrosis factor a substance that when present in normal amounts protects against TB infection and other diseases Paradoxically either a deficiency or an overkill of tumor necrosis factor can cause macrophages the host cells that gobble up pathogens to die by bursting and releasing the TB pathogens into a permissive extracellular milieu where they can grow exuberantly into corded mats the researchers said The researchers then discovered that corticosteroids which are in wide clinical use as

    Original URL path: http://mgm.duke.edu/news/tobin_2.html (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    one receptor that bound copper ions resulted in superior detection of even trace amounts of sulfur Underarm odors from bacteria skunk spray volcanic gases and odorized natural gas for leak detection are examples of sulfurous substances The work was published in the Proceedings of the National Academy of Sciences online the week of Feb 6 We learned that copper was the metal that allowed for detection of all the sulfur containing compounds we tested and it was Eric Block s idea that metal ions must be involved Matsunami said Further I see no reason why the mouse receptor activity would be different from human receptors because we have the same kind of olfactory receptors Block and colleagues created several dozen sulfur containing compounds for testing The odor impact of the sulfur containing molecule MTMT can be attenuated by manipulating the copper concentration in the nasal mucus The team did experiments using a chemical that binds to copper in the mouse nose so that copper wasn t available to the receptors and the mice didn t detect the MTMT Matsunami said This study establishes for the first time the key role of a metal namely copper in the activity of an olfactory receptor Eric Block said What s also exciting is that because olfactory receptors are transmembrane G protein coupled receptors GPCRs of the same type as receptors for drugs our discovery suggests a possibility that some drug receptor responses may also be enhanced in the presence of copper or other metal ions Other authors include Siji Thomas and Shaozhong Zhang of the University of Albany Department of Chemistry Timothy Connelly Qiuyi Chi and Minghong Ma of the Department of Neurobiology University of Pennsylvania School of Medicine and Xufang Duan Zhen Li Lifang Wu Guo Qiang Chen and Hanyi Zhuang all

    Original URL path: http://mgm.duke.edu/news/matsunami_3.html (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    at Tufts University will organize the Federation of American Societies for Experimental Biology FASEB conference as chair and co chair respectively As with previous conferences the 2013 FASEB Microbial Pathogenesis meeting will showcase the breadth and depth of the discipline with seminars from leading scientists in the field This long standing meeting bridges all disciplines of microbial pathogenesis including bacteriology virology parasitology mycology and immunology Its value to the scientific community is unique and cross disciplinary stimulating integration of multiple approaches Historically this meeting has brought leading young investigators to the attention of the broader community and has promoted new directions including development and application of heterologous host models analysis of new and emerging pathogens and novel appreciation of the diversity of host defenses As in past meetings the organizers seek to actively involve leading journal editors from the field including investigators who serve as editors and editorial board members and professional editors for Nature Nature Reviews Microbiology Cell Host Microbe PLoS Pathogens Molecular Microbiology mBio Eukaryotic Cell Infection Immunity the Journal of Bacteriology and the Journal of Virology and Virulence This forum effectively brings scientists and editors together to promote the dissemination of scientific advances and also provide insight

    Original URL path: http://mgm.duke.edu/news/faseb_2013.html (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    research findings Many of our returning fellows are alumni of the Duke sponsored Molecular Mycology and Pathogenesis Tri Institutional Training Program MMPTP that supports fellows at Duke University the University of North Carolina at Chapel Hill and North Carolina State University in Raleigh We look forward to bringing them together with current fellows and training faculty of the program as well as with outstanding colleagues from other institutions including Aaron

    Original URL path: http://mgm.duke.edu/news/mycology_symposium_2012.html (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    genes that allow Chlamydia to flourish in their hosts without the traditional lengthy process of domesticating the pathogen to accept recombinant DNA Valdivia said Our approach marries classical microbiology techniques with 21st century genome sequencing technologies If you encounter a new dangerous microorganism and want to determine what genes are important I think this represents an effective way to learn all we can as fast as we can One of the goals in studying microbial pathogens that harm humans and animals is to locate and disrupt the genes required for infection Valdivia said The microbe in this study Chlamydia is usually sexually transmitted hides in human cells and is a type of bacteria that must cause disease to be transmitted from one host to another Chlamydia is the leading sexually transmitted infection and a risk factor for pelvic inflammatory disease and infertility Prior to this work the function of many Chlamydia genes had to be inferred by their similarity to genes from other bacteria By isolating mutants that don t grow well inside cells and identifying the underlying mutations we can learn a lot about how these genes contribute to disease Valdivia said These are the activities we d like to block For us this significantly accelerates the analysis of Chlamydia and importantly should be applicable to many other microbes that have been difficult manipulate with recombinant DNA approaches he said Valdivia suggested that even microbes associated with our normal intestinal flora which are notoriously difficult to manipulate are now open to exploration so that we can learn how their genes influence human health including dietary disorders and inflammatory bowel disease The work was published on Jan 9 in the early edition of the Proceedings of the National Academy of Sciences Valdivia also said that the new technique could help

    Original URL path: http://mgm.duke.edu/news/valdivia_4.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    With this honor they join a very distinguished group of scientific leaders We are very fortunate to have so many people of this caliber on our faculty These are all outstanding scientists whom we are proud to have as colleagues said Sally Kornbluth PhD vice dean for basic science at Duke University School of Medicine They are also terrific citizens and leaders who make important contributions to the life of the Duke community This year s new AAAS fellows from the Duke University Medical Center are Richard Brennan PhD chair of the Duke Department of Biochemistry for distinguished contributions in the area of structural biology and his work deciphering mechanisms of gene expression and multi drug resistance Bryan Cullen PhD professor of molecular genetics and microbiology for distinguished contributions to the field of virology particularly for studies on human immunodeficiency virus and the role of microRNAs in viral pathogenesis Mariano Garcia Blanco MD PhD professor of medicine and professor of molecular genetics and microbiology for distinguished contributions in RNA biology and particularly for unraveling the importance of RNA protein interactions that regulate messenger RNA splicing and control pathogenic RNA viruses Sue Jinks Robertson PhD professor of molecular genetics and microbiology for distinguished contributions to the fields of genetics and molecular biology particularly for advancing the understanding of basic mechanisms of mutagenesis and homologous recombination of chromosomes Donald McDonnell PhD Glaxo Wellcome Professor of Molecular and Cellular Biology and chair of the Duke Department of Pharmacology and Cancer Biology for research that has provided fundamental insights into the molecular mechanisms underlying the pharmacological activities of nuclear receptor ligands in physiology and disease From Duke University the new AAAS fellows are Ingrid Daubechies PhD James B Duke Professor of Mathematics for her seminal work in wavelets as well as significant contributions in

    Original URL path: http://mgm.duke.edu/news/aaas_2012.html (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    placed on antibiotic treatments after birth which would wipe out some types of bacteria and yeast but once they were off the antibiotics and taking food the researchers expected to see more diversity of bacteria in the babies developing digestive systems than they found The findings were published in PLoS One open access journal on December 8 2011 Five infants had blood infections while three had necrotizing enterocolitis an infection related death of bowel tissue said Seed who is also with the Jean and George Brumley Jr Neonatal Perinatal Research Institute and the Duke Center for Microbial Pathogenesis Seed said that while the study babies were colonized mainly by organisms that were found in stool specimens in some cases they also had infections with Staphylococcus epidermidis a form of staph infection that was abundant in many of the babies digestive tracts The bacteria and yeast in the premature babies digestive tracts are known causes of devastating infections in these babies The gut seems to be a reservoir for some organisms that form infections Seed said Previous to this work we only knew the tip of the iceberg he said The researchers used genomic DNA typing of the bacteria fungi and parasites to determine which types were present It s not clear if the newborns are picking up these early infections from their mother s milk blood or in other ways or if the pathogens are from the environment surrounding the infants It s important to know where these pathogens come from so that doctors can possibly manipulate the babies environment or their digestive systems Seed said He noted that other studies had shown value for giving babies probiotic substances to tip the internal balance toward more favorable bacteria necessary for immunity and better health Seed stressed that certain bacteria and

    Original URL path: http://mgm.duke.edu/news/seed_1.html (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    Epilepsy is a difficult disorder to live with and it has a large impact on the lives of patients and their families said Nancy Andrews MD PhD dean of the Duke University School of Medicine This new center is a remarkable and powerful effort bringing together outstanding scientists from Duke and around the world to find important clues to understand and ultimately to treat epilepsy This grant allows us to study the genomes of epilepsy patients on a sufficiently large scale that we should be able to identify many new genes involved in the risk of epilepsy said principal investigator David Goldstein PhD director of the Duke Center for Human Genome Variation and the Richard and Pat Johnson Distinguished University Professor in the Department of Molecular Genetics and Microbiology Our hope is that these discoveries will provide validated targets for the development of new drugs and will help to determine how best to treat each individual patient based on their own genetic profile The center is administratively run by Daniel Lowenstein UCSF Samuel Berkovic University of Melbourne and Goldstein The grant will provide up to 25 million over five years to analyze the genomes of 4 000 epilepsy patients drawn

    Original URL path: http://mgm.duke.edu/news/goldstein_3.htm (2014-06-13)
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