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Information and Decision-Making in Dynamic Cell Signalling

Professor David Rand ( Mathematics Institute & Zeeman Institute for Systems Biology and Infectious Epidemiology Research, University of Warwick )

I will discuss a new theoretical approach to information and decisions in signaling systems and relate this to new experimental results about the NF-kappaB signaling system. NF-kappaB is an exemplar system that controls inflammation and in different contexts has varying effects on cell death and cell division. It is commonly claimed that it is information processing hub, taking in signals about the infection and stress status of the tissue environment and as a consequence of the oscillations, transmitting higher amounts of information to the hundreds of genes it controls. My aim is to develop a conceptual and mathematical framework to enable a rigorous quantifiable discussion of information in this context in order to follow Francis Crick's counsel that it is better in biology to follow the flow of information than those of matter or energy. In my approach the value of the information in the signalling system is defined by how well it can be used to make the "correct decisions" when those "decisions" are made by molecular networks. As part of this I will introduce a new mathematical method for the analysis and simulation of large stochastic non-linear oscillating systems. This allows an analytic analysis of the stochastic relationship between input and response and shows that for tightly-coupled systems like those based on current models for signalling systems, clocks, and the cell cycle this relationship is highly constrained and non-generic.

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