Margaret Clarke, Ph.D.

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

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.

Endosomes and V-ATPase in Dictyostelium labeled with TRITC-Dextran (red) and Green Fluorescent Protein (GFP).

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.

This material is based upon work supported by the National Science Foundation under Grant No. 0344541.

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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]

Chen, J., de Felipe, K.S., Clarke, M., Lu, H., Anderson, O.R., Segal, G., and Shuman, H.A. (2004). Legionella effectors that promote nonlytic release from protozoa. Science 303 , 1358-1361.

Clarke, M., Köhler, J., Heuser, J., and Gerisch, G. (2002). Endosome
fusion and microtubule-based dynamics in the early endocytic pathway of
Dictyostelium. Traffic 3, 791-800. [Movies]

Clarke, M., Köhler, J., Arana, Q., Liu, T., Heuser, J., and Gerisch, G. (2002). Dynamics of the vacuolar H⁺-ATPase in the contractile vacuole complex and the endosomal pathway of Dictyostelium cells. J. Cell Sci. 115, 2893-2905. [Abstract] [Movies] [Plasmid map]

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American Society for Cell Biology
American Society for Biochemistry and Molecular Biology
Biophysical Society
Society for Developmental Biology

Past service on review panels for the National Institutes of Health (Cell Biology and Physiology), the National Science Foundation (Cell Biology), and the American Cancer Society (Developmental Biology).