B.A., Mills College, 1965
Ph.D., University of California at Berkeley, 1971
Post-doctoral studies, University of California at San Francisco,
1972-76
Assistant to Full Professor, Albert Einstein College of Medicine,
Bronx, NY, 1976-1988
Joined OMRF Scientific Staff in 1988.
e-mail: Margaret-Clarke@omrf.ouhsc.edu
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My laboratory is studying how cells interact with material they take up from the environment. Cells ingest extracellular material via the related processes of pinocytosis (fluid uptake) and phagocytosis (particle uptake). These endocytic mechanisms allow cells to acquire nutrients, to destroy invaders, and also to become infected with certain pathogens. 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.
Endosomes and V-ATPase in Dictyostelium
labeled with TRITC-Dextran (red) and Green Fluorescent Protein
(GFP).
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Our major focus is the function and trafficking of the vacuolar proton pump (V-ATPase), which aids digestion of endocytosed material by acidifying the endosomal lumen. We are especially interested in how the enzyme is recycled in the endocytic pathway. We are also analyzing other aspects of the interaction of endosomes and phagosomes with the plasma membrane and with the cytoskeletal system. In related work, 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. Our studies emphasize high resolution light microscopy of living cells that are expressing fluorescent markers for organelles and proteins implicated in the endocytic pathway. (This work is supported by National Science Foundation Grant No. 0344541.)
Finally, in 2008 we began a collaborative research project using live cell microscopy to visualize the dynamics of conjugative pili. These filaments play an essential role in the horizontal transfer of DNA among bacteria, a process that contributes to the spread of antibiotic resistance. This work is a collaboration with Philip Silverman.
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Clarke, M., Maddera, L., Harris, R.L., and Silverman, P.M. (2008). F-pili dynamics by live cell imaging. Proc. Nat. Acad. Sci. USA 105, 17978-17981. [Movies]
Giorgione, J., and Clarke, M. (2008). Heterogeneous modes of uptake for latex beads revealed through live cell imaging of phagocytes expressing a probe for phosphatidylinositol (3,4,5)-trisphosphate and phosphatidylinositol (3,4)-bisphosphate. Cell Motil. Cytoskel. 65, 721-733. [Movies]
Chen, J., Reyes, M., Clarke, M., and Shuman, H.A. (2007). Host cell-dependent secretion and translocation of the LepA and LepB effectors of Legionella pneumophila. Cell. Microbiol. 9, 1660-1671.
Clarke, M., Müller-Taubenberger, A., Anderson, K., Engel, U., and Gerisch, G. (2006). Mechanically induced actin-mediated rocketing of phagosomes. Mol. Biol. Cell. 17, 4866-4875. [Movies]
Clarke, M., and Maddera, L. (2006). Phagocyte meets prey: Uptake, internalization, and killing of bacteria by Dictyostelium amoebae. Eur. J. Cell. Biol. 85, 1001-1010. [Movies]
Lu, H., and Clarke, M. (2005). Dynamic properties of Legionella-containing
phagosomes in Dicytostelium amoebae. Cell. Microbiol. 7, 995-107. [Movies] [PDF]
Click here for additional publications.
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