Julie Theriot: Cell Organization & Cell Motility

I. Cell Motility
II. Force Generation by Actin Assembly: Theories and Experiments
III. Principles of Cellular Organization: The Universal Cytoskeleton

Part II: Force Generation by Actin Assembly: Theories and Experiments

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Lecture Overview
This lecture covers the biochemical basis of actin-based motility (focusing on the pathogen Listeria as a model system for this process), the biophysical mechanism of polymerization-based force generation, and an evolutionary perspective of cell shape in prokaryotes and eukaryotes. The first part covers our understanding of how cells use the actin cytoskeleton to crawl. The pathogenic bacteria Listeria (which causes food poisoning) uses the actin cytoskeleton to propel itself in the cytoplasm and also invade other cells. This system has been an important model for understanding the actin cytoskeleton at the leading edge of a motile cell and for understanding host-pathogen interactions.

The second part is devoted to understanding how the polymerization of actin can produce, which is a current area of research in our laboratory. Here, I cover theories for how polymerization might be used to produce forces, and our efforts to test these models using optical traps, atomic force microscopes, and nanofabricated devices.

In the third part, I discuss how the complex shapes of cells are created by the cytoskeleton, and I compare and contrast prokaryotes (which have actin-, tubulin-, and intermediate filament -like proteins) and eukaryotes in this regard. In particular, I speculate that cytoskeletal dynamics were necessary to evolve simple bacterial shapes and cell division, but that additional layers of complexity (namely regulated nucleation and molecular motors) allowed eukaryotes to evolve more complex shapes and organize their internal components.

Speaker Bio
Julie Theriot grew up in Illinois and attended college at the Massachusetts Institute of Technology, graduating in 1988 with degrees in Physics and Biology. She pursued graduate training at the University of California at San Francisco with Dr. Timothy Mitchison, earning her Ph.D. in Cell Biology in 1993. After four years as a Whitehead Fellow at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, she moved to the Stanford University School of Medicine where she is currently a Professor in the Department of Biochemistry.

Theriot's research focuses on cell organization and motility, and on host-pathogen interactions in bacterial infections. She has won numerous awards including teaching awards from both Ph.D. and M.D. students. Theriot has also been awarded fellowships from both the David and Lucile Packard Foundation and the John D. and Catherine T. MacArthur Foundation.

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Related Articles

Fletcher, DA, Theriot JA. (2004) An introduction to cell motility for the physical scientist. Phys. Biol. 1(1-2):T1-10.
Rafelski SM, Theriot JA. (2004) Crawling toward a unified model of cell mobility: spatial and temporal regulation of actin dynamics. Annu. Rev. Biochem. 73:209-39.

Cameron LA, Giardini PA, Soo FS, Theriot JA. 2000. Secrets of actin-based motility revealed by a bacterial pathogen. Nat. Rev. Mol. Cell Biol. 1:110-9.

Hamon M, Bierne H, Cossart P. (2006) Listeria monocytogenes: a multifaceted model. Nature Rev. Microbiol. 4:423-34.

Cabeen MT, Jacobs-Wagner C. (2005) Bacterial cell shape. Nature Rev. Microbiol. 3:601-10.

Additional Reading
Parekh SH, Chaudhuri O, Theriot JA, Fletcher DA. (2005) Loading history determines the velocity of actin-network growth. Nauret Cell Biol. 7:1119-23
Soo FS, Theriot JA (2005) Adhesion controls bacterial actin polymerization-based movement. Proc. Natl. Acad Sci. U.S.A 102: 16233-8.

Mogilner A, Oster G. (2003) Force generation by actin polymerization II: the elastic ratchet and tethered filaments. Biophys J. 84:1591-605.

Dye NA, Pincus Z, Theriot JA, Shapiro L, Gitai Z. (2005) Two independent spiral structures control cell shape in Caulobacter. Proc. Natl. Acad. Sci. U.S.A. 102:18608-13.

Garner EC, Campbell CS, Mullins RD. (2004) Dynamic instability in a DNA-segregating prokaryotic actin homolog. Science. 306:987-9.

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