Network Dynamics and Cell Physiology

Complex networks of interacting proteins control the physiological properties of a cell (metabolism, reproduction, motility, etc.). Intuitive reasoning about these networks is often sufficient to guide the next experiment, and a cartoon drawing of a network can be useful in codifying the results of hundreds of observations. But what tools are available for understanding the rich dynamical repertoire of such control systems? How do these behaviors depend on the genetic and biochemical parameters of the system (gene dosage, enzymatic rate constants, etc)?  Using basic principles of biochemical kinetics, one can convert network diagrams into sets of ordinary differential equations and then explore their solutions by analytical and computational methods.

I will illustrate this approach with mathematical models based on the regulation of cell growth and diviion in eukaryotes. During normal growth and division, cell size is the critical parameter that drives progression from G1 to S/G2 to M phase and back to G1. Simple diagrams, which correlate Cdk activity with cell growth, give a new way of thinking about cell cycle control, particularly the role of checkpoint pathways in arresting the cycle. The method is generally applicable to any complex gene-protein network that regulates some behavior of a living cell.

John J. Tyson, Virginia Polytechnic Institute & State University

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