View source for Biology by design: reduction and synthesis of cellular networks

By Lingchong You, Duke University

'''Oct 21, 2008'''

CNLS Conference room.

:A central theme of our research is to better understand how cellular systems process diverse signals from the environment. We approach  this issue by analyzing both naturally existing cellular networks and  engineered ones.

:In this talk, I'll discuss ongoing work in analyzing the regulation  of mammalian cell cycle entry, focusing the concept of the  restriction point (R-point). The R-point marks the critical event  when a mammalian cell commits to proliferation and becomes  independent of growth stimulation. It is fundamental to normal  differentiation and tissue homeostasis and is dysregulated in  virtually all cancers. Although the R-point has been linked to  various activities involved in G1/S control, the underlying mechanism  remains elusive. Using single-cell measurements, we show that the Rb/E2F pathway functions as a bistable switch to convert graded serum  inputs into all-or-none E2F responses. Once turned ON by sufficient  serum stimulation, E2F can memorize and maintain this ON state,  independent of continuous serum stimulation. We further show that, in  both critical dose and timing responses, bistable E2F activation  directly correlates with a cell's ability to traverse the R-point.

:In addition to providing insights into cell cycle regulation, this  analysis provides inspiration for engineering synthetic gene circuits  to test basic design features of biological networks. To this end,  I'll discuss our efforts to engineer a simple bistable switch in  bacterium Escherichia coli, which have led to discovery of a novel  mechanism in generating bistable gene expression.

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