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  • Duke University Department of Molecular Genetics & Microbiology
    s Institute for Genome Sciences Policy Goldstein is the senior author of the paper As we expand the number of patients in future studies conducted by CHAVI researchers we aim to discover even more polymorphisms that could provide additional clues how some patients are better able to control the virus than others Goldstein This should ultimately lead to novel targets for vaccines the primary goal of CHAVI Two of the polymorphisms found were in genes controlling the human leukocyte antigen HLA system which plays a major role in the immune system by identifying foreign invaders and tagging them for destruction Two of the HLA genes known as HLA A and B are turned off by HIV when it enters the body which keeps the immune system from recognizing the virus as foreign HLA C however is not thought to be turned off by HIV 1 The new results suggest that for some individuals at least HLA C is involved in controlling HIV 1 Since HIV 1 appears unable to shut off HLA C unlike A and B HLA C may represent an Achilles heel of HIV according to Goldstein who said that a vaccine could be designed to elicit an HLA C mediated response which HIV 1 might be unable to defuse This study was the first time a genome wide approach has been used for an infectious disease Goldstein said Past studies have looked at individual candidate genes Since different people respond differently to infections a better understanding of how immune system genes control responses to infections should help us to design better treatments and more effective vaccines Added Haynes CHAVI was designed to do big science and the results of this analysis represent just the first of what should be many advances The technology used and collaborative efforts

    Original URL path: http://mgm.duke.edu/news/goldstein_1.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    his Ph D in Microbiology and Immunology at Stanford University School of Medicine Stanford California As a graduate student Dr Valdivia pioneered the use of fluorescent reporter proteins as probes for pathogen gene expression during host infection He and Dr Brendan Cormack developed green fluorescent protein mutants with enhanced fluorescent properties and applied flow cytometric techniques to identify bacterial genes that are specifically activated in infected cells This work led to the discovery of novel virulence factors in the enteric pathogen Salmonella typhimurium As a postdoctoral fellow at the Howard Hughes Medical Institute University of California Berkeley Dr Valdivia turned his focus to the genetic and biochemical analysis of protein sorting in the endosomal system of the model yeast Saccharomyces cerevisiae His postdoctoral work led to the discovery of a previously unrecognized function of a yeast clathrin adaptor protein complex in sorting membrane proteins in the Golgi and later in uncovering a role for cell stress signaling pathways in regulating the transport of cell wall biosynthetic enzymes to the plasma membrane As an independent investigator Dr Valdivia merged his expertise in microbial pathogenesis and cell biology to study the cellular microbiology of obligate bacterial pathogens His laboratory has established an

    Original URL path: http://mgm.duke.edu/news/valdivia_2.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    gene chop the genetic material RNA into bits called exons and then reassemble the bits in a different order to form a new RNA molecule In the process some of the exons are retained while others are excluded The exons that are retained in the final RNA determine which proteins the RNA produces within the cell The scissors that do the genetic chopping are in most cells proteins called splicing silencers and splicing enhancers In the current study Garcia Blanco s team sought to identify which silencers chop out an important segment of RNA in a gene called fibroblast growth receptor 2 FGFR2 This gene plays a critical role in normal mouse and human development and the order in which its RNA is assembled can alter an animal s development As a model system to study the scientists genetically created a glowing mouse The mouse carried in its FGFR2 gene a green fluorescent tag that would glow when a common type of silencer called an intronic silencer chopped out a specific exon called IIIb In this way the scientists could track whether intronic silencers were chopping out the IIIb exon and if so in which tissues and organs or whether other types of silencers or helper proteins were involved By tracking the green glow the team found that cells in most tissues made the same decision to silence exon IIIb but the cells used a variety of silencers and helper proteins to accomplish this task said Vivian I Bonano a graduate student in the University Program in Genetics and Genomics and lead author of the journal report Identifying which silencers are active in a given tissue or organ will ultimately help scientists understand how exons are erroneously included or excluded in various disease processes Bonano said For example a cell

    Original URL path: http://mgm.duke.edu/news/mariano1.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    system In our experiments we found that Chlamydia recruits lipid droplets from within the cell and stimulates the production of new droplets which cover the surface of the inclusion explained Yadunanda Kumar Ph D a post doctoral fellow in Duke s Department of Molecular Genetics and Microbiology This action of surrounding itself with lipid droplets may represent an example of organelle mimicry where the chlamydial inclusion is protected from the cell s defenses by being perceived by the cell as just another lipid droplet Kumar presented the results of the Duke research Dec 11 2005 at the 45th annual meeting of the American Society for Cell Biology in San Francisco The research was supported by National Institutes of Health the Pew Foundation and the Whitehead Foundation When these cloaked inclusions were treated with agents known to inhibit the production of lipid droplets the researchers were able to significantly reduce the ability of the bacterium to replicate It has long been thought that lipid droplets within cells were just passive repositories of energy for the cells said Duke microbiologist Raphael Valdivia Ph D senior member of the research team But now we are learning that these structures appear to play important roles in lipid synthesis and transport of cholesterol throughout the cell and cell signaling For their experiments the researchers studied Chlamydia trachomatis which is spread in humans by sexual contact and can lead to such disorders urinary tract infections eye infections and arthritis Because the bacterium is an obligate parasite researchers cannot directly manipulate its genes So the Duke team removed genetic material from the bacterium and inserted them into yeast cells which share many common structures and features with human cells When the researchers screened the chlamydial proteins in yeast cells they found four specific proteins that appeared to

    Original URL path: http://mgm.duke.edu/news/valdivia.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    fail to function properly allowing for the uncontrolled growth that forms a tumor We have a series of profiles that serve as signatures for those pathways Nevins said The specific changes in these pathways however can vary from person to person Using the methods of Nevins study doctors would be able to choose the drugs that are most likely to combat an individual patient s cancer While many drugs exist that target specific aspects of cancer deciding which ones to use can be a daunting task The fact of the matter is there are upwards of maybe 50 drugs that are developed that target specific components of cancer cells Nevins said But often tumors do not respond to a particular treatment noted Andrea Bild research associate at the Center for Genome Technology and lead author of the paper The advantage of this treatment is that we could target something we predict would be deregulated whereas other treatments take a more global approach she said A patient specific approach could help produce a higher survival rate There has been a major effort in the last several years to understand the pathways that drive cancer Colvin said Nevins explained that the complexities involving these different pathways pose a major difficulty in treating cancer I think most people would agree that a cure is not likely to happen with one drug he said Instead substantially effective treatments will involve using a combination of drugs Nevins said The next step in exploring the method will be clinical trials in which patients receive their own tailored treatments Since drugs that are already in use are known to target certain pathways researchers could profile a patient s specific case of cancer prescribe a combination of drugs based on that profile and look for an increase in

    Original URL path: http://mgm.duke.edu/news/nevins2.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    on site of infection and infections in humans are highly lethal if not immediately treated Dr Aballay has developed a new model for dissecting the ways pathogens such as the plague can infect and kill their hosts said Pamela Marino Ph D scientist at the National Institute of General Medical Science This creative approach should improve our ability to develop new medicines to treat such diseases Aballay has used the C elegans a worm commonly found in the soil as a model to study the virulence mechanisms of other bacteria besides plague The worm is an ideal model for genetic studies he said because it takes only three days to develop from an embryo to an adult capable of reproducing Also scientists can easily manipulate specific genes in the worm and in contrast to other animal models large quantities of the worms can be grown quickly and can even be frozen and used later C elegans lives in the soil so it continually comes into contact with bacteria and other microbes Aballay said It has a highly developed system for not only recognizing bacteria but also responding to them The ability of its innate immune system to respond appropriately to specific bacteria is very similar to that of mammals Aballay tested Y pestis in his model because another research team recently reported that the bacterium killed C elegans by creating a biofilm over the worm s pharynx causing it to die of starvation Since mammals infected with Y pestis do not die in this manner Aballay believed that other virulence factors were involved in infecting the worm We thought that a Y pestis strain known as KIM5 that lacks the genes hmsHFRS operon required for biofilm formation could still enter the worm s digestive system and eventually kill it by

    Original URL path: http://mgm.duke.edu/news/plague.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    to actually predict which cells carried the oncogenes and their associated deregulated pathways Having validated the approach in cells and then in mice the Duke team assessed its ability in human tumors as well Their first success was distinguishing two types of lung cancer from each other adenocarcinoma which originates in the periphery of the lung and squamous cell carcinoma which forms in the central chest area They found the overwhelming majority of adenocarcinomas were deregulated for the oncogene Ras while only a tiny minority of squamous cell carcinomas exhibited Ras deregulation Hence deregulation of the Ras pathway is an important signature of adenocarcinomas but not of squamous cell carcinoma said Nevins The Duke scientists then applied the approach to a series of breast cancer cell lines They predicted which pathways were likely to be deregulated then treated the cancer cells with drugs that targeted components of the cancer causing pathways Indeed the pathways predicted to be most highly deregulated were also the most sensitive to drugs that targeted these pathways Until now there have been very few opportunities to guide the use of therapeutic drugs that target specific cellular components said Nevins director of the Center for Applied Genomics and Technology at the Duke Institute for Genome Sciences and Policy But now we ve developed tools to measure the activity of critical pathways groupings of related genes and proteins that are activated or silenced in a given tumor and we can potentially use this information to best utilize the large array of existing drugs The ultimate goal of their approach is to provide individualized treatment plans to each patient based on the unique pathway signatures of their tumor said Mike West Ph D professor of statistics and decision sciences at Duke and a lead author of the study Pre

    Original URL path: http://mgm.duke.edu/news/nevins.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    Petes studies genomic instability and chromosomal abberrations commonly found in cancer cells This year academy members elected 196 new fellows and 17 new foreign honorary members The 213 men and women are leaders in scholarship business the arts and public affairs and include Nobel Prize winning physicist Eric Cornell of the University of Colorado Supreme Court Chief Justice William Rehnquist and Steven Squyres leader of NASA s Rover program for

    Original URL path: http://mgm.duke.edu/news/petes2.htm (2014-06-13)
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