Genetic analysis of post-developmental Rho GTPase signaling: identification and characterization of Rho signaling pathways required during the C. elegans immune response. (360G-Wellcome-088409_Z_09_Z)

Rho signaling pathways have been extensively studied in cell-based assays however the importance of these pathways in whole adult organisms remains unclear. My previous work has shown that adult C. elegans can be used as a model to study post-developmental roles of Rho signaling. Here I am focusing on the role of Rho in altering cell morphology during the C. elegans innate immune response. Using RNAi feeding libraries and forward genetic approaches my research will identify the upstream regulato rs and downstream effectors of Rho required for this process. In addition I will exploit my work demonstrating that Rho and MAPKinase act together to alter cell morphology during this response in order to dissect the interactions between these two pathways. A key goal of this research is to identify Rho signaling pathways important for the control of cell morphology in adult animals and to understand how these pathways interact with others. Understanding these signaling pathways will provide insights into Rho s role in normal cell function during processes such as innate immunity and is likely to tell us more about how mis-regulation can lead to immunological defects and diseases such as cancer. Drugs that target these effectors may have therapeutic benefit.