CAREER: Multi-input Multi-output Cellular Control: Bacterial Type III Secretion as a Model System

University Of California-San Francisco, San Francisco CA

Investigators

Abstract

Voigt 0547637 The objective of this research is to develop computational and experimental methods to quantify how a network integrates inputs from multiple sensors and chooses amongst multiple cellular responses. It is often challenging to quantify how signals are integrated because the stimulus that activates a sensor is unknown or difficult to control in culture. In Aim 1, chimeric sensors will be constructed where the kinase activity can be varied using small molecule inducers. Multiple chimeras will be used to determine the underlying logic operations performed by a regulatory network. In Aim 2, a general methodology will be developed to determine how a cell population bifurcates between multiple co-regulated responses. These methods will be applied to the Salmonella regulatory network controlling type III secretion as a model system of multi-input multi-output control. Two educational programs will be developed to train high school, undergraduate, and graduate students in methods to understand and engineer complex biological systems. First, a new core graduate course will be designed to teach techniques from transport phenomena, kinetics, and non-linear dynamics to problems in biology. Second, a diverse student team, including high school students, will be organized to compete in an intercollegiate genetic engineering competition (iGEM), the goal of which is to design and build a synthetic organism.