Anne C. Hart
We are using genetic, molecular, cellular and behavioral approaches in C. elegans to study nervous system. The nematode C. elegans is uniquely suited for this analysis -- the nervous system consists of only 302 neurons whose location and synaptic connections are all known. Yet, this small nervous system is remarkably similar to vertebrate nervous sytems. The C. elegans genome is almost completely sequenced, facilitating cloning and molecular analysis of interesting mutations.
One focus of the lab is how animals detect and respond to external stimuli. We hope to identify both the proteins which act as sensory receptors and to learn how sensory information is encoded by the nervous system as synaptic activity. We address these questions in C. elegans by studying ASH sensory neurons which detect mechanical, osmotic and chemical stimuli. We focus our attention on mutations which perturb response to just one stimulus, leaving intact response to the other stimuli detected by ASH, in order to identify proteins specifically involved in stimulus detection and synaptic signaling. Mutations have been identified which specifically prevent response to each of the different stimuli detected by ASH. Only two of these genes have been cloned so far. Analysis of glr-1, a gene required for nose touch response, suggested that synaptic output from ASH differs, either qualitatively or quantitatively, depending on the stimulus detected by ASH. Ongoing analysis of the osm-10 gene, required for osmotic avoidance, suggests that osm-10 encodes a novel protein involved in signal transduction. We have also identified mutations which specifically perturb response to volatile repellants. We suspect that genes required for response to just one stimulus will be involved in stimulus detection or in synaptic signalling.
Two additional projects are underway in the laboratory. 1) We are testing C. elegans model system for studying Huntington's disease. In humans, expansion of a triplet repeat domain in the Huntington's gene causes neurodegneration, dementia and chorea. We have induced neuronal cell death in C. elegans with mutant huntingtin protein. 2) We are also in the midst of identifying C. elegans neuropeptides. Diverse neuropeptides play critical roles in the nervous system, yet they have not been studied in a genetic system. C. elegans neuropeptide genes will be characterized and "knocked out" to address their role in nervous system function and development.