8 May 2009
Jason Locasale
Cantley Lab
Division of Signal Transduction
Beth Israel Deaconess Medical Center
In response to stimuli, cells utilize complex signal transduction pathways that contain many interacting molecular components. These interactions cooperate to form complex networks conferring multiple layers of regulation. How this regulation that results from multiple points of crosstalk and feedback control is exploited to achieve an appropriate phenotypic response is a subject of intense study. In this talk, I will discuss a simple method to evaluate the collective dynamics and as a result, the dominant regulatory modules in models of complex biochemical pathways. The method involves computing a singular value decomposition that expands the time courses of the model into linear combinations of characteristic modes that govern the model dynamics. The resulting modes provide a hierarchical interpretation of the essential dynamics in the pathway and reveal the key regulatory network structures (e.g. feedback controls) that determine these dynamics. I will discuss the method in the context of a model of growth factor signaling in mammalian cells.