SGER: Signaling Mechanisms in Eucaryotic Gradient Sensing

University Of Florida, Gainesville FL

Investigators

Abstract

0328599 Narang Eurcaryotic cells usually move by crawling in response to an external concentration gradient. The goal of this work is to understand the mechanism of directional sensing, the phenomenon that allows cells to "read" the gradient and take the first step of crawling motion, namely extension and a protusion. Though many signal transduction pathways involved in directional sensing have been discovered over the past 5 years, the manner in which the pathways interact to produce accurate and sensitive directional sensing is still unknown. The PI has formulated the first mechanistic mathematical model that integrates the pathways and predicts dynamics that are consistent with the existing experimental data. The PI proposes to develop a firm understanding of the directional sensing mechanisms in eurcaryotic cell motion. The main components are: 1) Application of a novel microfluidic device for generating stable chemo-attractant gradients and 2) Application of state-of-the-art imaging techniques to rigorously test the validity of the PI's model and competing models. The techniques include fluorescence microscopy and Fluorescence Resonance Energy Transfer (FRET). The goal of this SGER is to initiate experimental tests of the model, specifically to identify the signal transduction mechanisms that amplify shallow chemo-attractant gradients into polarized phosphoinositide distributions. Understanding the mechanisms of cell movement has broad impact in areas of medicine in which cell migration plays an important role, e.g., cancer metastasis, wound healing, inflammation response, and embryo development.