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  • Duke University Department of Molecular Genetics & Microbiology
    and their associated G proteins said Heitman This novel class of G proteins which if proven to be conserved in humans could play a role in allowing our cells and bodies to sense unique signals important in both health and disease Heitman said The researchers study focused on a yeast G protein coupled receptor called Gpr1 that is coupled with a G protein called Gpa2 Functionally the Gpr1 receptor senses glucose in the yeast cells environment and activates the coupled Gpa2 to launch a growth process in which the yeast cells elongate and produce filaments that extend away from the colony and into the growth medium to forage for nutrients G proteins are heterotrimeric complexes meaning that they are composed of three different subunit proteins called alpha beta and gamma each of which plays a role in the transmission of the metabolic signal to the cell s machinery Since Gpa2 is highly related to the alpha subunit the researchers expected to find associated beta and gamma subunits but they were not present According to Heitman absence of these two subunits raised questions of whether the GPa2 functioned alone or whether there existed as yet undiscovered classes of G protein subunits Consider the analogy of a relay race Heitman said To run a relay you typically need four runners or swimmers If any one is missing the baton cannot be passed So in this signaling pathway who was passing the baton from the first runners to the last runners Were they skipping a runner or was there a novel runner that we didn t know about Those questions led Heitman and his colleagues to identify three novel G protein subunits two closely related subunits called Gpb1 and Gpb2 and a third called Gpg1 The newly discovered subunits offer an example of

    Original URL path: http://mgm.duke.edu/news/archives/switches.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    regulate classes of mRNAs during cell growth and development The model predicts that functionally related groups of mRNAs are coordinately regulated at the posttranscriptional level by specific mRNA binding proteins that recognize common sequences in the mRNAs The modes authored

    Original URL path: http://mgm.duke.edu/news/archives/model.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    efficient inactivation of gene function using specifically designed RNA molecules The method involves the design and synthesis of small RNAs that are complementary in sequence to a target mRNA Expression of the small RNAs can efficiently block the translation of the target mRNA and thus eliminated the production of the protein product The method described in a series of recent publications by Bryan Cullen in the Department of Molecular Genetics

    Original URL path: http://mgm.duke.edu/news/archives/artificial.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    the National Institute of Allergy and Infectious Diseases Unlike bacteria or viruses fungi are eukaryotic cells that resemble cells of the human body Fungal infections can thus be difficult to treat Heitman said The majority of transplant recipients suffer one or more infections and these infections are a significant cause of morbidity and mortality Cryptococcal infections occur to two to three out of every 100 transplant recipients and is associated with a 50 percent mortality rate Candida albicans which can cause thrush esophagitis or vaginitis is the most common fungal infection and is common in hospital settings Heitman said these findings open the door to the clinical use of drug combinations and could lead to the identification of additional drug targets There s an ongoing need to develop better antifungal drugs There is an increasing population of people who are at risk and some infections prove very difficult to treat Heitman said There are relatively few drugs to treat these infections some have serious side effects and drug resistant isolates have emerged For some fungal infections such as aspergillus infections in the lung and cryptococcal infections in the brain there is a 50 percent risk of death These studies reveal new ways in which existing drugs can be combined to combat fungal infections and improve therapy he said Combining fluconazole with either cyclosporin or FK506 was previously found by other researchers to potently kill fungal cells in the test tube and had been proposed as an approach to combat difficult to treat fungal infections The multi drug antifungal treatment concept was tested in mice in 2000 by a research team led by Dominque Sanglard an investigator at the CHUV Hospital in Lausanne Switerzerland and an international scholar of the Howard Hughes Medical Institute Their studies demonstrated that the combination of

    Original URL path: http://mgm.duke.edu/news/archives/fungal.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    said However the Duke study goes beyond this past work by developing predictive analyses of breast cancer clinical status an important aspect of the future use of this technology in the clinic A DNA microarray also known as a gene chip allows researchers to examine thousands of genes from a single tumor sample In using the chips to measure gene activity the scientists extracted messenger RNA mRNA the result of expression of a tumor s genes from each of the tumors They then applied the mRNA from each tumor to a chip where the mRNA transcribed from a particular gene interacts with the gene sample on the microarray The scientists use fluorescent markers on the mRNA to measure the level of mRNA thus reading out which genes are actively expressed in which tumor The chips used by the Duke researchers were commercial microarrays which consist of about 7 000 human genes In their analysis they concentrated on 100 genes whose activity maximally reflected the outcomes in the tumors They used their statistical analytical approach to analyze the gene expression profiles of 49 tumor samples previously tested to be either positive or negative for estrogen receptors These gene expression profiles revealed clear differences in the patterns of gene expression in breast tumors that could predict the estrogen receptor status of the tumors Nevins said The determination of estrogen receptor status is an important aspect of breast cancer diagnosis because of its role in promoting tumor growth It also has implications for therapies Although an analysis for estrogen receptor can be done now the use of gene expression analysis provides much more detailed information about the nature of estrogen receptor status in these tumors Nevins said The PNAS study also reported the results of gene profiling of breast tumors to predict their lymph node involvement In their profiling the scientists compared tumors that had spread to lymph nodes at the time of diagnosis to those that had not They found that statistical analysis of the profiles suggested the potential to classify tumors lymph node status although the accuracy was less than that of the estrogen receptor analysis According to Nevins DNA microarray analysis can be compared to examining the individual pixels of a digital photo rather than only being able to view the overall scene Instead of examining a tumor under a microscope one day physicians will likely have the technology to examine the individual genes of a tumor he said Large scale gene expression information holds the promise of improved clinical diagnosis and treatment strategies but it depends on developing statistical tools needed to analyze the data Nevins said Also the scientists said the ability to predict lymph node status using gene profiling could in many cases obviate the need for the extensive and risky surgery involved in removing lymph nodes Mike West director of the Duke Institute of Statistics and Decision Sciences and lead author of the study developed and conducted the statistical analysis in the study in collaboration with

    Original URL path: http://mgm.duke.edu/news/archives/genomics.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    will coordinate the consortium s activities from its Research Triangle Park N C headquarters Dr David Schwartz chief of pulmonary medicine at Duke and principal investigator for the Duke effort said that a number of specific Duke projects will focus on asthma pulmonary fibrosis neurodevelopmental aspects of disease as well as the effects of exposure to different metals on health Even in simple genetic disorders there is wide variation in the severity of disease Schwartz said Genetics is only a part of the complex issue of disease development We want to understand more about how different outside factors interact with genes in determining how or if a particular disease occurs The researchers plan to subject well known animal models of disease such as mice zebrafish and worms to such known environmental stressors as bacterial infection malnutrition and exposure to metals Using an approach called gene expression profiling the researchers can screen thousands of genes at a time to detect subtle genetic differences between models that appear unaffected by a particular environmental stress and those that succumb to disease As candidate genes are identified in animal models the corresponding genes in humans will be tested to see if the environmental stressors have the same effect If the gene in question does appear to play a role in disease Schwartz explained new therapies can be targeted to that gene By the end of five years we hope to be able to use this approach to discover new proteins that can be of importance in the development of human disease Schwartz explained These discoveries can lead to new targets for potential drugs or it can help us identify particular susceptible individuals who might be at a higher risk for disease This marks the third recently established genomics project under the umbrella of the

    Original URL path: http://mgm.duke.edu/news/archives/grant.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    using longitudinal meta genomic data and in vitro model community experiments to figure out what causes post illness secondary succession I am particularly interested in the possible role of phage predation and changing oxygen concentration If we understand this process we can direct medical interventions to support healthy development of host associated microbiota I also do research with Justin Wright Duke Biology in abandoned agricultural fields where I use greenhouse studies field experiments and modeling to ask what is the relative importance of predation resource availability and plant traits in determining the rate and pattern of woody plant invasion I completed by undergraduate work at Yale where I did research at the macro scale including using morphology to understand the force of ecology in the evolution of pika and how the ecology of fear affects community dynamics I hope to continue asking similar questions but at both the macro and micro level in my dissertation Publications Reese A T C D Ficken A Braswell and J B Heffernan Invited Approaches for testing alternative stable states a quantitative review Ecosystems Sargis E J N Woodman N C Morningstar A T Reese and L E Olson 2014 Island history affects faunal composition the treeshrews Mammalia Scandentia Tupaiidae from the Mentawai and Batu Islands Biological Journal of the Linnean Society 111 290 304 Sargis E J N Woodman N C Morningstar A T Reese and L E Olson 2013 Morphological distinctiveness of Javan Tupaia hypochrysa Scandentia Tupaiidae Journal of Mammalogy 94 938 947 Strickland M S D Hawlena A T Reese M A Bradford and O J Schmitz 2013 Trophic cascade alters ecosystem carbon storage and release PNAS 110 11035 11038 Reese A T H C Lanier and E J Sargis 2013 Skeletal Indicators of Postcranial Specialization in Pika Mammalia Ochotonidae Journal of

    Original URL path: http://mgm.duke.edu/faculty/david/lab/durand.html (2014-06-13)
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  • Duke University Center for Microbial Pathogenesis
    Date July 1 6 2007 Location Melbourne Australia Purpose To present talk and poster Abstract Extreme serum sensitivity of yeast thr1 mutants due to homoserine accumulation The threonine pathway is interesting from the perspective of antifungal drug targets since it does not exist in humans is conserved throughout fungi and various threonine biosynthetic mutants have deleterious phenotypes in addition to threonine auxotrophy We found aspartate kinase hom3 homoserine kinase thr1 and threonine synthase thr4 mutants of a clinically derived S cerevisiae strain unable to survive in mice and in particular thr1 and thr4 mutants were severely depleted after only 4 hours in vivo Consistent with this these mutants were extremely sensitive to incubation in serum a phenotype that was conserved for Candida albicans thr1 mutants while Cryptococcus neoformans thr1 mutation was lethal Serum sensitivity results from accumulation of the pathway intermediate homoserine since we find homoserine to be toxic to thr1 and thr4 mutants and mutation of genes required for homoserine production HOM3 and HOM6 block serum sensitivity Increasing levels of threonine overcomes the serum and homoserine sensitivity of thr1 mutants therefore the toxic effects of homoserine may be due to homoserine acting as a threonine analog Homoserine and serum toxicity is also blocked by cycloheximide consistent with a role for protein synthesis in the sensitivity We therefore hypothesize that homoserine replaces threonine in proteins resulting in aberrant proteins In low threonine environments such as serum a higher homoserine threonine ratio would result in increased homoserine misincorporation thus a higher degree of aberrant proteins and a higher level of toxicity Name Stephanie Diezmann Lab Dietrich Conference XXIII International Conference on Yeast Genetics and Molecular Biology Date July 1 6 2007 Location Melbourne Australia Purpose To present talk and poster Abstract Resistance to hydrogen peroxide in Saccharomyces cerevisiae is a quantitative

    Original URL path: http://mgm.duke.edu/microbial/training/awards_3.htm (2014-06-13)
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