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  • Duke University Center for Microbial Pathogenesis
    to solve of combating infection said St John who is in the Duke NUS Program in Emerging Infectious Diseases The synthetic granules consist of a carbohydrate backbone that holds tiny encapsulated inflammatory mediators such as tumor necrosis factor TNF These particles when injected mimic the attributes of the granules found in natural cells and the synthetic particles also target the draining lymph nodes and provide for the timed release of the encapsulated material Traditional vaccine adjuvants may help antigens the small part of a pathogen that is injected during vaccination that the body reacts to to persist so the body can have an immune reaction and build antibodies so that when a real pathogen such as the flu virus arrives it will be conquered Alternatively adjuvants may activate cells called dendritic cells which pick up pathogen parts and must travel from the skin to lymph nodes where immune reactions are initiated The Duke team however has created a vaccine adjuvant of nanoparticles that are capable of traveling from the point of injection to the lymph nodes where they act on many cell types of the immune system to spur the right reaction for a greatly increased immune response The researchers found that they could use this adjuvant in vaccinations of mice with the influenza A virus In levels of flu virus exposure that would be lethal in typical mice the vaccinated mice were able to fight off the disease and had an increased survival rate thanks to the effective immune response the particles stimulated The researchers also showed they could load the same type of particles with a different immune factor IL 12 that directed a response toward a different set of lymphocytes This is an important finding since certain types of infections require specialized responses to be overpowered by

    Original URL path: http://mgm.duke.edu/microbial/news/abraham_2.html (2014-06-13)
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  • Duke University Center for Microbial Pathogenesis
    in our zebrafish model but also in people said Tobin who is also with the Duke Center for Microbial Pathogenesis People with different versions of this gene appear to be vulnerable for opposite reasons either too little inflammation or too much So people with different gene variants might benefit from different therapies targeted to their individual genotypes Seok Yong Lee PhD an assistant professor in the Duke Department of Biochemistry and member of the Duke Ion Channel Research Unit will use the funds to uncover the chemical and physical secrets of ion channels which help critical processes occur at lightning speed throughout the body Lee said of the news I am very excited I wouldn t be able to win this award without the support of the Biochemistry Department and the Duke Ion Channel Research Unit With this award we plan to study biophysics and pharmacology of the voltage gated sodium channel Nav1 7 which has potential to provide new insights into future analgesic pain reduction development Nicolas Buchler PhD is an assistant professor with joint appointment in the departments of biology and physics and also an investigator in the Institute for Genome Sciences Policy He will use his award to develop computer simulations and lab experiments in yeast to understand the extent to which the single celled organisms gene networks can learn and predict the statistical regularities of their environment Charles Gersbach PhD an assistant professor of biomedical engineering at the Pratt School of Engineering plans to develop technologies to create new therapies for muscular dystrophy or heart disease by regenerating new cells to replace faulty or missing ones This involves reprogramming the gene expression of easily accessible cells such as a patient s own skin cells to create new muscle bone cartilage blood vessel or heart tissue cell

    Original URL path: http://mgm.duke.edu/microbial/news/nih_innovators_1.html (2014-06-13)
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  • Duke University Center for Microbial Pathogenesis
    picture of how a formerly tropical fungus could find new territory for infection in temperate climates Importantly we found that isolates causing the outbreak and those infecting AIDS patients are completely different VGII vs VGIII said co lead author Edmond Byrnes PhD a recent graduate from the Heitman laboratory Wenjun Li PhD also a co lead author and researcher in the Heitman laboratory noted that based on the fungal isolate samples taken from patients those with C gattii may experience resistance to the commonly used azole drugs that combat fungal infections and clinicians might be better aware of potential treatment problems if they knew the species Because cryptococcal strains are responsible for over 620 000 deaths annually and responsible for one third of all AIDS deaths this species distinction may be of public health importance There may be an unrecognized health burden in AIDS patients attributable to C gattii rather than C neoformans Heitman said He said that while a simple test is all that is needed to distinguish the two strains few clinical microbiology labs or hospitals even in developed countries are equipped to distinguish C neoformans from C gattii Heitman said that he doesn t believe that there is any human to human transmission of C gattii but rather patients are being exposed in the environment For example one AIDS patient from San Diego had an isolate that was traced back to a type of tree which is a common place to find C gattii in Australia and elsewhere This study clearly illustrates that AIDS patients in certain areas of the world might be infected by two different cryptococcal species said J ohn R Perfect MD professor of medicine at Duke University Medical Center Although the outcome of infection in comparison between the two species remains uncertain this

    Original URL path: http://mgm.duke.edu/microbial/news/heitman_10.html (2014-06-13)
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  • Duke University Center for Microbial Pathogenesis
    the human cell from committing suicide when it senses that it has been invaded by a pathogen a common self defense mechanism giving Chlamydia bacteria an extended chance to multiply and stay hidden The study was the cover story in the July 21 print edition of Cell Host and Microbe Microbiologists and genetics experts led by Raphael Valdivia PhD an associate professor in the Duke Department of Molecular Genetics and Microbiology completed the work that narrowed down the search to an enzyme that chlamydia produces a protease called CPAF Chlamydia makes this master protease that takes over the whole cell and prevents it from mounting an effective pathogen killing immune response Valdivia said Chlamydia is unique among pathogens in that it can co exist within humans without causing symptoms for a long time This reflects a careful balance between the host and the pathogen We think CPAF is central to this balance Therefore if we disarm it we can tilt the equation toward the human host and mount an effective immune response that will not only clear the infection but prevent it from re emerging The Duke chemists led by Dewey McCafferty PhD a professor in the Duke Departments of Chemistry and Biochemistry designed a molecule that could block the CPAF activity inside of human cells Typically to design a potent specific and cell permeable inhibitor is a complicated undertaking and inhibitor designs don t work right away McCafferty said But in this case it worked on the first try Professor Valdivia s group of microbiologists and my group of chemical biologists worked to establish which qualities we needed to incorporate into a CPAF inhibitor The results are very exciting because we have an inhibitor lead molecule that may form the basis for a new class of anti chlamydial drugs

    Original URL path: http://mgm.duke.edu/microbial/news/valdivia_5.htm (2014-06-13)
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  • Duke University Center for Microbial Pathogenesis
    Serology 1974 1982 and Clinical Mycology and Mycobacteriology 1974 1991 sections of the Duke Hospital Clinical Microbiology Laboratory He also served as the Program Director of the tri institutional Molecular Mycology and Pathogenesis Training Program 2003 2011 which is the only NIH funded training grant that specifically supports postdoctoral fellows engaged in research focused on fungi as model organisms or pathogens of plants or animals His contributions to medical education span 32 years 1975 2007 During this time he organized and taught the internationally recognized Duke Summer Mycology Course and Medical Mycology and was a small group laboratory instructor director in the first year course of Microbiology and The Body and Disease He also served as the study program director for Microbiology and Infectious Diseases His publication record includes 85 research papers and 68 chapters and reviews I have had the pleasure to work very closely with Tom for the last 18 years here at Duke said Joseph Heitman MD PhD Chair of the Department of Molecular Genetics and Microbiology Tom has been a truly outstanding faculty member a leader in the field of medical mycology a tireless mentor for students and post doctoral fellows and a very active member

    Original URL path: http://mgm.duke.edu/microbial/news/mitchell_2.htm (2014-06-13)
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  • Duke University Center for Microbial Pathogenesis
    When the scientists performed an experiment that made the smaller spores grow into larger spores We found in that case the smaller spore that became large acted like the larger spores Lee said We believe that this spore bypassed the natural growth stage of isotropic growth and that was how it becomes more virulent This means we might be able to find a way to arrest them in the smaller stage before they grow into more virulent larger spores he said Interestingly other scientists have recently published related findings about the dual cell sizes in another virulent fungal pathogen Cryptococcus neoformans in which gigantic cells form in the lungs of infected animals and patients Normally immune cells called macrophages engulf and destroy dangerous fungal spores Small spores can be contained by macrophages but the larger spores switch too quickly to hyphal growth and thereby can destroy the macrophage When the macrophages a first line defense split open they undergo cell death and are unable to protect an infected human or other host animal This finding shows another example of adaptation through fungal cell gigantism which lets pathogenic fungi establish infection in the hosts particularly those that are immune compromised said Joseph Heitman MD PhD co senior author and chair of the Duke Department of Molecular Genetics and Microbiology We used a diabetic model of mice which is also an immunocompromised type of animal We found the fungal subspecies that we studied is highly virulent in mice which correlates well with this subspecies frequent occurrence in clinical human specimens Heitman said the hope is to find a way to arrest the isotropic growth stage Clinically these mucor infections are reasonably common in diabetic patients transplant patients and lung cancer chemotherapy patients he said Having a high blood glucose level is immunosuppressive

    Original URL path: http://mgm.duke.edu/microbial/news/lee_soo_chan.html (2014-06-13)
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  • Duke University Center for Microbial Pathogenesis
    for how fungal and other microbial pathogens evolve and emerge to cause disease and outbreaks said Heitman The work on Cryptococcus is becoming increasingly important as harmful and new forms of the fungus have emerged outside of the tropics causing an ongoing outbreak in Canada and the Pacific Northwest in the US Globally Cryptococcus causes more than one million infections annually including more than 600 000 attributable deaths and nearly one third of all AIDS associated deaths Heitman s genetic and evolutionary findings on this pathogen serve as a model to further our understanding of other fungi and parasites causing human infections augmenting the recent discoveries of same sex mating of Candida albicans by Richard Bennett and colleagues at Brown University and selfing in outbreaks of Toxoplasma gondii revealed by Michael Grigg and co workers at the NIH This R37 MERIT Award recognizes the transformative insights that Dr Heitman s work has provided on the evolutionary origins of sexual reproduction from his work on fungi said Arturo Casadevall MD PhD a globally recognized authority on infectious diseases and Chair of the Department of Microbiology and Immunology at the Albert Einstein College of Medicine in New York City Heitman said he was humbled and honored at the news that this grant application had achieved a perfect score and was chosen for a MERIT Award This is a terrific reflection of our robust institutional environment for studies on microbial pathogenesis and genetics and also on the partnership among investigators in basic science departments and physician scientists in the clinical departments at Duke said Heitman This award in many ways can be attributed to the tremendous long term collaboration I have had with John Perfect MD Professor in the Division of Infectious Diseases and the Department of Medicine and other clinical colleagues as

    Original URL path: http://mgm.duke.edu/microbial/news/heitman_9.html (2014-06-13)
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  • Duke University Center for Microbial Pathogenesis
    release signaling chemicals to create an immune response The scientists chose to study dengue virus which is common in Singapore because mosquitoes inject the virus through the skin and skin is rich in mast cells They found that mice lacking mast cells had more of the virus in their lymph nodes and increased infection after measured injection with a small dose of dengue virus compared to mice with normal levels of mast cells The mast cells produce chemokines which in turn help to bring some special killer cells into the infected skin to fight and contain the virus It was an important discovery for the field to learn that mast cells could be activated by pathogens like bacteria or parasites St John said We were excited to learn that mast cells also respond to and promote the clearance of a viral infection The finding is important because to date there are no vaccines or effective therapies for dengue fever said senior author Soman Abraham PhD professor of pathology and mast cell expert also in the Program in Emerging Infectious Diseases St John said that the finding opens new paths to explore Because mast cells are involved in airway reactions as during an asthma attack this new finding might also help scientists study viral infection in the lungs airways and sinuses She noted that other mosquito borne viruses could also be studied in terms of mast cell response like the West Nile virus Now that we know mast cells can recognize viruses we can better understand how that infection process begins Abraham said Knowing the important role of mast cells in viral infections could help find ways to prevent these infections perhaps in the form of vaccines Because mast cells can be deliberately activated and also shut down with small molecules

    Original URL path: http://mgm.duke.edu/microbial/news/abraham_1.html (2014-06-13)
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