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THOMAS POLLARD

Our laboratory uses a combination of biochemistry, biophysics, microscopy and fission yeast genetics to investigate the molecular basis of cellular motility and cytokinesis. Actin-based cellular movements are essential for shaping organs during embryonic development, defense against microorganisms and wiring the nervous system. Movement of cells out of primary tumors is the chief cause of mortality in cancer. Cytokinesis is essential for the replication of all cells and is still one of the least understood aspects of cell division.

Recent accomplishments include the discovery and characterization of Arp2/3 complex, an assembly of two actin-related proteins and seven novel subunits. We determined the crystal structure of Arp2/3 complex and developed a method to visualize the growth of actin filaments in real time by fluorescence microscopy. These breakthroughs have opened the way to understand how Arp2/3 complex forms branches on the sides of actin filaments. We have also mapped out the temporal and spatial pathway for the assembly and constriction of the contractile ring during cytokinesis in fission yeast. We also developed methods to count proteins inside live cells, so we can determine the absolute number of proteins in any cellular structure.

Actin-based movements: We study how cells control the assembly and disassembly of actin filaments during cellular movements. We have projects on the structure and function of actin, Arp2/3 complex, activators of Arp2/3 complex (such as the Wiskott-Aldrich syndrome protein, WASp), profilin, ADF/cofilin and capping protein. We use fluorescence microscopy of proteins tagged with fluorescent fusion proteins to follow the time course of the interactions of these proteins during endocytosis in fission yeast.

Cytokinesis: We study the mechanism of cytokinesis using the fission yeast S. pombe as a favorable model organism to learn how cells pinch themselves in two when they divide. In particular we are investigating the early steps in the assembly of the contractile ring by formins, proteins that grow actin filaments while remaining attached to the end of the elongating polymer. Projects include analysis of proteins that regulate actin assembly and the activity of myosin-II, the motor that constricts the contractile ring.

Selected Publications
Wu, J. -Q. and Pollard, T. D. Counting cytokinesis proteins globally and locally in fission yeast. Science 310, 310-314 (2005)

Kovar, D. R., Harris, E.S., Mahaffy, R., Higgs, H. N. and Pollard, T.D. Control of the assembly of ATP- and ADP-actin by formins and profilin. Cell 124, 423-435 (2006)

Nolen, B. and Pollard, T. D. Insights into the influence of nucleotides on the actin family of proteins from seven crystal structures of bovine Arp2/3 complex. Mol. Cell 26, 449-457 (2007)

Wu, J-Q., Kuhn, J. R., Kovar, D. R. and Pollard, T. D. Spatial and temporal pathway for assembly and constriction of the contractile ring in fission yeast cytokinesis.  Devel. Cell 5, 723-734 (2008)

Paul, A. and Pollard, T. D.  The role of the FH1 domain and profilin in formin-mediated actin filament elongation and nucleation.  Curr. Biol. 18, 9-19 (2008)

Last Updated 04-14-08