Shotgun siRNA Perturbation Dissect Growth Factor Triggered Proliferation Migration Signaling Systems

Shotgun siRNA Perturbation to Dissect Growth Factor Triggered Proliferation and Migration Signaling Systems Air date: Wednesday, December 02, 2009, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local Category: Wednesday Afternoon Lectures Description: Cells make use of an elaborate control system that integrates inputs from multiple receptors, computes this information and makes decisions about key cellular outputs such as cell migration and proliferation. Our laboratory is focusing on discovering the rules that govern these decision processes by perturbing signaling steps, by monitoring signaling events and cell functions, and by employing mathematical modeling. We have developed a number of novel biosensors and microscopy techniques to monitor cell signaling and functional processes over time, developed novel chemically induced enzyme activities for rapid signaling pathway perturbations and created a set of 3000 RNAi's to perturb signaling pathways by selectively reducing the expression of most human signaling proteins (shotgun perturbation strategy. We are particularly intrigued by the roles of calcium, lipid second messenger and small GTPases in the spatial and temporal coordination of cellular responses and a current focus of the laboratory is on the questions how cells polarize and collectively migrate and how they proliferate in response to growth factor stimuli. This talk will give a general introduction into how to investigate complex signaling systems and in a second part focus on growth factor-triggered collective migration of endothelial cells. Using live cell imaging and systematic siRNA perturbations, we identified a modular control structure for this collective migration process. A third part of the talk will focus on an interlinked positive feedback system that we discovered using this same systematic perturbation strategy. This control system allows quiescent cells stimulated by growth factors to decide in an all-or-none fashion whether they will remove a barrier protein and enter the cell cycle. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. Runtime: 01:03:30 Permanent link: http://videocast.nih.gov/launch.asp?15469