Graduate Training in Neuroscience
University of Washington
James H. Thomas
Professor, Department of Genome Sciences
Understanding how the nervous system develops and generates complex behaviors is one of the great challenges facing biologists. My laboratory uses genetic and molecular approaches to study the nervous system of the nematode C. elegans . The worms entire nervous system has just 302 neurons whose detailed structure and interconnections have been determined by electron microscopy. Studies in the lab focus on three behaviors. The first is the formation of the specialized dauer larva, which is regulated by environmental factors that are sensed and interpreted by the nervous system. We have analyzed interactions among many genes that regulate dauer formation and have shown that they function in specific and orderly, though complex, pathways. These functional pathways correspond to the information processing that underlies dauer formation. These pathways include a cGMP-mediated sensory process, an intercellular TGF-beta pathway, and an insulin-like receptor pathway. The other two behaviors under study are egg laying and defecation. Even these lowly activities are surprisingly complex and interesting. Both behaviors are mediated by known motor neurons and muscles and involve several familiar neurotransmitters, including serotonin, acetylcholine, and GABA. The lab has identified a large set of mutants that perturb the excitiation of egg-laying and defecation muscles by the nervous system. Included amoung these genes are seven that encode potassium channel subunits of a variety of types. These channels are expressed in specific subsets of C. elegans neurons and muscles. One goal of this project is to delineate the full set of ion channels that characterize each neuron and muscle, an effort that is helped by the nearly complete genome sequence. We have also shown that one of these genes encodes a calcium/calmodulin dependent kinase II (CaMKII) and genetic interactions suggest that we have identified targets of this regulatory protein kinase.