Select a year 2001 2002 2003    Select a researcher Alan G. Barbour, M.D. William Bishai, M.D., Ph.D. Martin J. Blaser, M.D. John C. Boothroyd, Ph.D. Jon Clardy, Ph.D. Peter Cresswell, Ph.D. Roy Curtiss, III, Ph.D. Ronald W. Davis, Ph.D. Jack E. Dixon, Ph.D. Stanley Falkow, Ph.D. Gerald R. Fink, Ph.D. Richard A. Flavell, Ph.D. Lee Gehrke, Ph.D. Laurie H. Glimcher, M.D. Jeffrey I Gordon, M.D. Daniel L. Hartl, Ph.D. William R. Jacobs, Jr., Ph.D. Keith A. Joiner, M.D., co-PI Karla Kirkegaard, Ph.D. Roberto G. Kolter, Ph.D. W. Ian Lipkin, M.D. Richard M. Locksley, M.D. Carl Nathan, M.D. Peter Palese, Ph.D. Pradipsinh K. Rathod, Ph.D. David A. Relman, M.D. Charles M. Rice, Ph.D. Alexander Rich, M.D. Lee W. Riley, M.D. David S. Roos, Ph.D. Abigail A. Salyers, Ph.D. Gary K. Schoolnik, M.D. Iwona Stroynowski, Ph.D. Ronald P. Taylor, Ph.D. Elisabetta Ullu, Ph.D. John Waitumbi, D.V.M., Ph.D Select a project A Gnotobiotic Zebrafish Model for Analyzing Symbiotic Host...Antiviral Effects of Interferon-Inducible Cytosolic ProteinsArming the Immune System against Pathogens with Selective ...Bacterial Pathogen Families that Function in Both the Anim...Cellular Genes and Viruses: Who Wins The War?Conditional Targeted Deletions in Plasmodium falciparum...Designing and Mining Pathogen Genome Databases: The Apicop...Development of Genetic Systems for Genetically Intractable...Development of New Genetic Tools to Identify Nutrient Upta...Ecological Influences on Pathogen Genome EvolutionEvolution of Virulence in Eukaryotic PathogensExploiting an Evolutionary Omission in Pathogenic RNA Viru...Exploring Novel Pathways of Immune Defenses Against Orally...Genomic Approach to Improved Immunogenicity of M. tuber...Genomic tools to characterize hypermutating Plasmodium fal...Investigation of Mechanisms Leading to Anemia at Low Paras...Molecular definition of the bacterial population of human ...Mycobacterium Tuberculosis Latency and Reactivation Tuberc...New Antibiotics from Environmental DNAOptimizing Immunity to Complex Pathogens In VivoPandora's Box ProjectProviding an Economic Benefit to Using a Vaccine to Enhanc...Resistance Gene Flow in the Human Colonic MicrofloraRole of Nucleotide Binding Domain-Leucine Rich Repeat Prot...Sexually Transmitted Disease Agents in the “Healthy” Human...Systematic Analysis of Positive-strand RNA Viral Transmiss...The Human Intestinal Microbiome: Community Analysis, Host ...The Molecular Ecology of Vibrio cholerae in the Gangetic D...The Natural History of Typhoid Infection in VietnamThe Role of Quorum Sensing in Fungal DiseaseTowards Broad-spectrum Antivirals: Functional Screens for ...Transmission Blocking Vaccines for TuberculosisTransmission-blocking Vaccines Against Arthropod VectorsViral Pathogenic Mechanisms Involving Z-DNA Binding Proteins Select an institution Albert Einstein College of Medicine of Yeshiva University Columbia University Harvard Medical School Harvard School of Public Health Harvard University Johns Hopkins School of Public Health Massachusetts Institute of Technology Mount Sinai School of Medicine New York University School of Medicine Rockefeller University Stanford University School of Medicine Stanford University School of Medicine, VA Palo Alto Health Care System University of California - Berkeley University of California - Irvine University of California - San Diego University of California - San Francisco University of Illinois - Urbana-Champaign University of Pennsylvania University of Texas Southwest Medical Center University of Virginia University of Washington Washington University Washington University School of Medicine Weill Medical College of Cornell University Whitehead Institute for Biomedical Research Yale University School of Medicine

Gerald R. Fink, Ph.D. Whitehead Institute for Biomedical Research

Fungal infections have emerged as a worldwide problem of appalling dimensions because of the AIDS epidemic. Although fungi of all types afflict immunocompromised individuals, Candida albicans is the most frequent cause of disease. One key to Candida’s pathogenesis is its ability to switch from a yeast form to a filamentous form. This switch is controlled by many environmental factors, interaction with cells of the immune system, and potentially by quorum sensing (small signaling molecules that inform microorganisms about their density). The analysis of filamentation in the model system, baker’s yeast, revealed that a key molecule required for dimorphism is an adhesin, a member of a family of cell-surface glycoproteins. These proteins are responsible both for the switch between the yeast and filamentous form, for the attachment of fungi to epithelial and endothelial cells, and for the attachment of fungal cells to each other. EDT1, one of the genes required for filament formation in Candida, appears to be regulated by cell density. The edt1 mutants fail to form filaments under many conditions that induce wild type to switch from yeast to filamentous forms. The edt1 mutant strains also show severe defects in adherence to plastic surfaces. Moreover, overstatement of EDT1 brings about filamentous growth in the absence of agents normally required for induction of filamentation. At high density the EDT1 transcript is completely stable, but at low density, the transcript level is reduced 10-fold in less than 5 minutes. Experiments will be designed to determine whether there is an extracellular factor that stabilizes the EDT1 transcript levels at high cell density. Mutants and whole genome arrays will be used to identify other genes that respond to cell density. These low/high density experiments will be performed in parallel using Saccharomyces for comparison with Candida. Genes that respond to density will be identified and their functions in filamentation and virulence determined.

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