Monday, October 5, 2015
Computing and Mathematical Sciences Colloquium
Mathematical and Experimental Frameworks to Study Fluctuations in Cells
Professor Johan Paulsson, Associate Professor, Department of Systems Biology, Harvard University
All intracellular processes involve components present in low numbers, creating spontaneous fluctuations that in turn can enslave the components present in high numbers. The mechanisms are often complex, with reaction rates that depend nonlinearly on concentrations, indirect feedback loops, and distributed delays. Most systems are also sparsely characterized, with a few steps known in detail but many important interactions not even identified. I will present exact mathematical frameworks for deriving limits on behavior in such systems, for example showing how hard it is to tightly control processes that involve bursts, delays, or finite signaling rates - regardless of the nature of the control networks. I will also discuss various ways of designing experiments to rigorously exploit conditional independences in fluctuations to infer underlying mechanisms, without having to guess the nature of feedback loops or interacting processes. Finally I will present some experimental results, on the design of synthetic genetic networks and on the connection between stochastic gene expression and DNA repair.