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More about Genetic Models of Disease Research Program
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Research Interests Our experimental system is Dictyostelium discoideum, a small soil amoeba that is easily cultured and is amenable to molecular genetic analysis, and whose endocytic behavior closely resembles that of mammalian macrophages. We have several areas of focus. First, we are examining the role of the vacuolar proton pump (V-ATPase), which aids digestion of endocytosed material by acidifying the endosomal lumen. We are using mutational analysis to elucidate enzyme function and Green Fluorescent Protein (GFP) fused to a V-ATPase subunit to monitor proton pump trafficking along the endocytic pathway. Second, we are examining the interaction of endosomes and phagosomes with the plasma membrane and with the cytoskeletal system. Finally, we are exploring how Legionella pneumophila, the bacterial pathogen that causes Legionnaire's disease, manages to subvert the phagocytic pathway to avoid digestion and then utilize the modified phagosome as a compartment for replication. Using fluorescent markers for both Legionella and the organelles and proteins implicated in the infection process, we are characterizing the process of infection in living cells. Movies showing the work described above may be found at http://mcbi.ouhsc.edu/clarke. Our research is supported by grants from the National Science Foundation (MCB-344541) and the Oklahoma Center for Science and Technology (HR05-020). Joined OMRF Scientific Staff in 1988. Mailing Address
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