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

Kirschner, Marc

Title:

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

dc.contributor.author	Kirschner, Marc	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
dc.date.accessioned	2012-02-07T20:15:22Z
dc.date.available	2012-02-07T20:15:22Z
dc.date.issued	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.identifier.uri	http://hdl.handle.net/1853/42368
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	Moving Image
dc.type.genre	Lecture
dspace.entity.type	Publication
local.contributor.corporatename	College of Sciences
local.contributor.corporatename	School of Biological Sciences
local.contributor.corporatename	Center for the Study of Systems Biology
local.relation.ispartofseries	Distinguished Lecture Series in Systems Biology
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