Date: Tue, October 10, 15:30-17:30
Place: Room An301, An Block, IIS, The University of Tokyo
Invited Speaker: Prof. John J. TYSON (Virginia Polytechnic Institute & State University)

Title: NETWORK DYNAMICS AND CELL PHYSIOLOGY

Abstract:
Complex networks of interacting proteins control the physiological 
properties of a cell (metabolism, reproduction, motility, signaling, 
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? Why does a control system behave the way it 
does? What other behaviors are possible? How do these behaviors depend 
on the genetic and biochemical parameters of the system (gene dosage, 
enzymatic rate constants, equilibrium binding constants, etc)?  Using 
basic principles of biochemical kinetics, we convert network diagrams 
into sets of ordinary differential equations and then explore their 
solutions by analytical and computational methods. We illustrate this 
approach with a mathematical model of cell cycle transitions in 
eukaryotes, based on a molecular network controlling the activity of 
cyclin-dependent kinase (Cdk). In this model, arrest points in the 
cell cycle correspond to stable steady states of the control system. 
As biochemical parameters of the control system change, these arrest 
points are imposed or lifted by transitions called "bifurcations." 
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.