The long-term objectives of this work are to elucidate the molecular basis of mechanosensation in the nematode C. elegans. The identification of genes which regulate the mechanosensory apparatus in C. elegans touch cells will also serve to define elements required for neurodegeneration since specific touch-related mutations can induce neuronal lysis. Deletion analysis of putative functional domains within proteins directly involved in degeneration will be performed and will facilitate subsequent studies designed to isolate genes encoding proteins that interact with these domains to regulate neuronal responses. Alternative approaches involving genetic screens for modulators of mechanosensation and detection of protein-protein interactions in vivo, using the yeast two- hybrid system are proposed to identify novel regulatory genes and characterize interactions between existing genes. The implications of this work lie in the possibility that these nematode genes will provide insights into mechanisms of human nerve cell death. Additionally, based on homology to mammalian counterparts, several of these genes appear to encode components of ion channels. Thus, these studies are also relevant to our understanding of disorders related to ion transport.
