Dynamical Modularity in Regulation of Mammalian Proliferation

When: Thursday, November 15, 2012 at 1:30 pm
Where: DA 5th fl
Speaker: Erzsébet Ravasz
Organization: Medicine at the Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School
Sponsor: Joint Network Seminar

Endothelial cells form the inner lining of all blood vessels. They display remarkable phenotypic heterogeneity across the vasculature, unparalleled by most mammalian cell types. They serve the diverse needs of tissues, but also mediate or aggravate diseases such as cancer, atherosclerosis and sepsis. In the process they coordinate a diverse arsenal of context-dependent phenotypes, many of which are well characterized in isolation. Understanding their coordination into complex responses, however, remains a problem and lacks adequate dynamical modeling, limiting our ability to alter disease states of the endothelium. For example, interventions to alter new blood vessel growth to starve off tumors or replenish oxygen-poot tissues are of limited success. The regulatory processes that maintain proliferative or quiescent endothelial phenotypes are nearly universal in all cell types. In endothelial cells, these processes are wired together with endothelial specific regulatory circuits such as VEGF signaling, flow-mediated signals and endothelial inflammation. As a first step towards building dynamical models of their coordination, we assembled three simple dynamical models of the mammalian cell cycle, DNA damage and DNA synthesis, and connected them into a multi-module dynamical model. Here, we present evidence of hierarchical modularity in this regulatory system, manifest not in its network structure, but rather, in its functional dynamics.