Timothy J. Mitchison

Department of Systems Biology
Harvard Medical School
Warren Alpert Building, Room 541B
200 Longwood Avenue
Boston, MA 02115
Tel: (617) 432-3805
Fax: (617) 432-5012
Email: Timothy_Mitchison@hms.harvard.edu
8 postdoctoral fellows, 7 graduate students

My lab is interested in the structure, dynamics, and function of the cytoskeleton. We use imaging-based assays in living cells and in vitro extracts, in conjunction with molecular biology and biochemical fractionation approaches, as well as theory and modeling. Most of of the lab works on cell division in some way. One major focus is on the mechanism of mitotic spindle assembly in Xenopus egg extracts. We use a variety of imaging methods, including single molecule imaging, to probe protein localization and dynamics, biochemistry and pharmacology to perturb assembly, and theory/modeling to rationalize the results. We are increasing interested in an applied problem, cancer chemotherapy directed at the mitotic spindle. We are performing imaging and biochemistry experiments in different cancer cell lines to understand how current chemotherapy works, and how we might improve it. A key question is to understand differences between cell types in drug response. Part of the lab works on how the actin cytoskeleton is organized, during cytokinesis and also in the comet tails of Listeria, a pathogenic bacterium. Current foci include understanding monopolar cytokinesis, and the mechanism by which actin filaments turn over rapidly in the cytoplasm.

Our lab is increasingly interdisciplinary. Through the Institute of Chemistry and Cell Biology we pursue discovery of new small molecule probes, typically by screening small molecule libraries for perturbation of mitosis or cytokinesis in living cells, or for inhibition of key proteins involved in these processes. As part of the new department of Systems Biology, we are increasingly interested in modeling cytoskeletal processes, and developing new tools for measuring pathways and processes in living cells. These interdisciplinary directions revolve around collaborations with Chemistry, Physics and Mathematics groups from all round the university.

References:

• Burbank KS, Groen AC, Perlman ZE, Fisher DS, Mitchison TJ. (2006) A new method reveals microtubule minus ends throughout the meiotic spindle. J Cell Biol. 175(3):369-75.
• Brieher WM, Kueh HY, Ballif BA, Mitchison TJ. (2006) Rapid actin monomer-insensitive depolymerization of Listeria actin comet tails by cofilin, coronin, and Aip1. J Cell Biol. 175:315-24.
• Vrabioiu AM, Mitchison TJ.(2006) Structural insights into yeast septin organization from polarized fluorescence microscopy. Nature. 443:466-9.