New approaches to studying the growth and size regulation of mammalian cells

Show simple item record Kirschner, Marc en_US 2012-02-07T20:15:22Z 2012-02-07T20:15:22Z 2012-01-24
dc.description Marc Kirschner, John Franklin Enders University Professor, Chair and Professor of Systems Biology, Department of Systems Biology Harvard Medical School presented a lecture on Tuesday, January 24, 2012 at 11 am in Room 1116E of the Klaus Advanced Computing Building on the Georgia Tech campus. en_US
dc.description Runtime: 63:36 minutes en_US
dc.description.abstract 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. en_US
dc.format.extent 63:36 minutes
dc.language.iso en_US en_US
dc.publisher Georgia Institute of Technology en_US
dc.subject Cell growth en_US
dc.subject Suspended microchannel resonator en_US
dc.subject Cell mass en_US
dc.title New approaches to studying the growth and size regulation of mammalian cells en_US
dc.type Lecture en_US
dc.type Video en_US
dc.contributor.corporatename Harvard Medical School. Dept. of Systems Biology en_US
dc.contributor.corporatename Georgia Institute of Technology. Center for the Study of Systems Biology en_US

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