Marc Kirschner, Harvard University, "New approaches to studying the growth and size regulation of mammalian cells"

Jan 24 2012, 11:00 am
Distinguished Lecture Series Guest Speaker: 

Marc W. Kirschner, Ph.D.

John Franklin Enders University Professor
Chair and Professor of Systems Biology
Harvard University

Date & Time: 
Tuesday, January 24, 2012, 11:00AM
Klaus 1116E
Jeffrey Skolnick
The study of cell growth has been limited primarily by the lack of accurate enough means of measuring the growth of cells as they traverse the cell cycle. There are several theoretical models of growth that have been impossible to evaluate because the methods for measuring growth have been too inaccurate to distinguish among them. In particular, if cells grow proportional to their mass, which of course doubles each cell cycle, then it is likely that the variation in cell size in a population would increase without limit. This is simply because cell division is rarely completely symmetric, producing smaller cells that would grow slower and larger cells that would grow faster. On the other hand, if cells added equal mass per unit time this undesirable outcome could be avoided. There are ideas that size control may not exist but simply be driven by exogenous and independent controls of cell cycle and growth, size being simply a resultant of these explicity controls. Yet the very strict size regulation of different cell types, suggests that cell size is an evolutionary optimum for different functions and hence, cells should have a homeostatic mechanism for maintaining cell size. There are other speculations that cells grow to a defined size and then divide, making cell division a slave to cell growth. The opposite is also possible that passage through the cell cycle feeds back on cell growth. To approach these questions we have developed two new analytical techniques of exquisite sensitivity. In collaboration with Scott Manalis at MIT, we used his suspended microchannel resonator to measure cell mass to 0.01% and to do that for as many as 8 generations without causing any known harm to the cells. This technique pointed to a sharp transition of growth at the G1/S transition. It also shows that a size threshold does not exist in a mammalian cell line but instead there is convergence of cell growth rates at G1/S. Another technique which Ran Kafri, a postdoc in my lab and Galit Lahav’s lab developed used a static population based approach to derive very sensitive kinetic features based on the ergodic assumption of steady state growth. This method opens up many new measurements not possible in growing individual cells; here temporal resolution and sensitivity is increased markedly as cell numbers exceed a million. This method also described a period at the feedback on growth rate at the G1/S transition. These new measurements suggest that there is a sizing mechanism in mammalian cells that reduces variation in the cell cycle by affecting growth rate and size dependence of growth rate . Such a mechanism is liked to be tuned and respond differently in different cell types and under different conditions.
Additional Info: 

Marc W. Kirschner, Ph.D. is founding chair of the Department of Systems Biology. He and John Gerhart are co-authors of Cells, Embryos, and Evolution (Blackwell, 1997) and their newly published book, The Plausibility of Life: Resolving Darwin¹s Dilemma (Yale University Press, 2005). Dr. Kirschner was elected Foreign Member of the Royal Society of London and as a Foreign Member of the Academia Europaea in 1999. In December 2003, Kirschner received the E.B. Wilson Medal, the American Society of Cell Biology¹s highest scientific honor. He is a member of the National Academy of Sciences and the American Academy of Arts and Sciences, and has served on the Advisory Committee to the Director of the National Institutes of Health and as President of the American Society for Cell Biology. Dr. Kirschner¹s laboratory investigates three broad, diverse areas: regulation of the cell cycle, the role of cytoskeleton in cell morphogenesis, and mechanisms of establishing the basic vertebrate body plan.

In 1993, Dr. Kirschner arrived at Harvard Medical School from the University of California, San Francisco, where he had served on the faculty as Professor for fifteen years. Dr. Kirschner graduated from Northwestern University in 1966 and received his Ph.D. from the University of California, Berkeley in 1971. Following postdoctoral research at Berkeley and at the University of Oxford, he was appointed an Assistant Professor at Princeton University in 1972.

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