Timothy Mitchison

Harvard Medical School, Department of Systems Biology
Alpert Building, Room 541B
200 Longwood Ave.
Boston, MA 02115
Tel: 617-432-3805
Email: timothy_mitchison@hms.harvard.edu

Website:

mitchison.hms.harvard.edu 
Lab Size: Between 10 and 15

Summary

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.

Publications

Kueh, H.Y., Brieher, W.M., & Mitchison, T.J. (2010). Quantitative analysis of actin turnover in Listeria comet tails: evidence for catastrophic filament turnover. Biophysical Journal, 99(7), 2153-2162. PMID: 20923649. PMCID: PMC3042591.

Yang, R., Niepel, M., Mitchison, T.K., & Sorger, P.K. (2010). Dissecting Variability in Responses to Cancer Chemotherapy Through Systems Pharmacology. Clinical Pharmacology and Therapeutics, 88(1), 34-8. PMID: 20520606. PMCID: 2941986. pdf.

Mitchison, T.J. (2010). Cell biology: How cilia beat. Nature , 463(7279), 308-309. PMID: 20090745.

Needleman, D.J., Groen. A., Ohi, R., Maresca, T., Mirny, L., & Mitchison, T. (2010). Fast microtubule dynamics in meiotic spindles measured by single molecule imaging: evidence that the spindle environment does not stabilize microtubules. Molecular Biology of the Cell, 21(2), 323-333. PMID: 19940016. PMCID: PMC2808228.

Huang, H.C., Shi, J., Orth, J.D., & Mitchison, T.J. (2009). Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly. Cancer Cell, 16(4), 347-358. PMID: 19800579. PMCID: PMC2758291. pdf.

Dumont, S. & Mitchison, T.J. (2009). Compression regulates mitotic spindle length by a mechanochemical switch at the poles. Current Biology, 19(13), 1086-1095. PMID: 19540117. PMCID: PMC2722833. pdf.