Marc Kirschner


Chair, Department of Systems Biology
Harvard Medical School
Warren Alpert Bldg., Room 536
200 Longwood Avenue
Boston, MA 02115
Tel: (617) 432-2250
Fax: (617) 432-0420
Email: marc@hms.harvard.edu
10 postdoctoral fellows, 5 graduate students


Our lab has focused on understanding cell morphogenesis, cell proliferation, and cell signaling by combining biochemical, cell biological, and embryological approaches. We have attempted to ask what controls cell motility and polarity on a molecular level, how is information concerning cell morphology communicated to the cell from external sources, and how do developmental processes such as gastrulation control directed cell movement. We have concentrated on Cdc42 and Rac-1 dependent actin nucleation in extracts and have identified novel components downstream of these small GTPases likely to be involved in lamellopodia or filopodia formation, membrane potrusions required for directional cell motility. We are in the process of extending our in vitro findings to study the onset of polarized cell motility at gastrulation in Xenopus embryos.

 

Our studies of cell proliferation concern primarily the regulation of several important proteolysis systems in mitosis and G1. We have used both Xenopus and mammalian cultured cell extracts for the study of the anaphase promoting complex/cyclosome (APC), which controls the degradation of important regulators of anaphase, including cyclin and the anaphase inhibitor, Pds1. APC serves as a nexus for cell cycle checkpoint controls and for the proper regulation of chromatid separation. We have purified many of the components involved in cell cycle progression and our current aim is to understand how these serve to coordinate the sequence of events in mitosis and in the G1 phase of the next cell cycle. We are utilizing a novel mass spectrometic based quantification system to accurately define the order of events in mitosis and G1, and to identify novel components of the cell cycle and differentiation machinery.

 

Our studies in developmental biology concern early patterning and motility events in gastrulation, as well as a modelling based understanding of the Wnt-signaling and BMP pathways. In the hope of identifying the evolutionary origins of vertebrate patterning we have examined the hemichordate, Saccoglossus, which shows several key features of vertebrate and arthropod organization. We have combined developmental and genome studies in this organism to better understand the origins of the chordate nervous system and the Spemann Organizer.

 

 

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BBS webpage updated 12/02/2009