Identification and characterization of novel regulators of mammalian cell morphogenesis using RNAi. (360G-Wellcome-083548_Z_07_Z)

Actin filaments form a dynamic skeleton beneath the plasma membrane of animal cells and are crucial for cell morphogenesis. As a result, defects in cytokeletal regulation contribute to a variety of human diseases. Until recently, however, efforts to identify the mammalian genes involved were limited by the difficulties of studying essential genes in whole animals, so the set of genes currently investigated are a biased group. But the sequencing of several animal genomes and the discovery of ds RNA-mediated interference (RNAi) has enabled unbiased screens to identify known and novel genes involved. In the past year, the Baum lab has used genomic information to generate a human siRNA library targeting all known conserved actin regulators, and they have performed a genome-wide RNAi screen in Drosophila cell culture for novel actin regulators. Here, I propose to use RNAi to perform a comparative functional analysis of the complete set of actin regulators in fly and mammalian cell culture. I will then characterize several novel genes that play a conserved role in the regulation of the actin cytoskeleton. This will be one of the first studies to use unbiased loss of function genetics to identify genes involved in the regulation of animal cell form.