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Dr. Clarke:

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Dr. Clarke's CV in brief

Publications

Genetic Models of Disease Research Program

Dr. Clarke In The News

A Lethal Exchange: OMRF researchers uncover clue in spread of "superbugs"

Margaret Clarke, Ph.D. Member, Genetic Models of Disease Research Program James P. Hannigan Distinguished Scientist

Research Interests
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.

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 filament 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.

Movies showing the work described above may be found at http://gmd.omrf.org/clarke.

Joined OMRF Scientific Staff in 1988.

Mailing Address
Genetic Models of Disease, MS 48
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, Oklahoma 73104

Contact Information
Phone: (405) 271-7660
Fax: (405) 271-7312
E-mail: Margaret-Clarke@omrf.org