The goal of this research is to define the underlying physical processes that guide the collective and emergent behaviors of closely interacting groups of epithelial cells. The small GTPase Ras is important in both intracellular and intercellular signaling networks, and the tools and concepts to be developed in this study will elucidate how Ras regulates multiple emergent behaviors of groups of cells as they undergo development. The project will reveal how Ras, as a key signaling node in pathways downstream of growth factor receptors, couples its activity across multiple time and length scales to orchestrate complex and emergent phenomena in groups of cells. The central hypothesis to be tested is that whereas the absolute level of Ras activity in single cells controls the physical properties of cell motility, cohesion, and autocrine secretory profiles, in groups of epithelial cells it is the relative level of Ras activity between cells that determines their emergent behaviors. These emergent behaviors may be attributed to a competition between the processes of differential motility, differential adhesion (or cohesion), and the community effect (autocrine loops). The hypotheses will be tested using advanced chemical biology tools, live cell imaging and mathematical modeling. Broader impacts: This project will directly provide quantitative and cross-disciplinary training to two graduate students. Training will include synthetic chemistry, cell biology, quantitative video microscopy, and mathematical modeling. To broaden the impact of the project, computational modules from these studies will be incorporated into a course on distributed control in multicellular systems.
