ARRA: Analysis of the Regulation of G Protein Coupled Sensory Signaling in C. Elegans

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). Intellectual Merit All animals rely on their ability to sense and respond to their constantly changing environments to survive. Because they do not have eyes or ears, C. elegans (small roundworms) depend heavily upon their ability to taste and smell chemical information in their soil environment to find food and avoid danger; animals must move towards chemicals that indicate a food source while avoiding chemicals that indicate potentially harmful environments. These behavioral responses are elicited when the chemical signals (tastants and odorants) bind to proteins (receptors) on sensory nerve cells (neurons) and initiate a chain of intracellular events that ultimately activates the neuron. Neuronal activity, in turn, controls the behavior of the organism. Although this process of chemical signal transduction is highly conserved across species, there are still large gaps in our understanding of the mechanisms used to regulate signaling. Coupled with powerful genetic and molecular tools, C. elegans is an ideal model system in which to dissect the contributions of individual genes and regulatory pathways to integrated neuronal function and sensory behavior. Loss of a negative regulator of signaling (C. elegans GRK-2) surprisingly leads to decreased calcium signaling in sensory neurons and a concomitant loss of both attractive and avoidance chemosensory behaviors. In the absence of GRK-2 there appears to be an upregulation of compensatory inhibitory pathways that dampen signaling to protect neurons from overstimulation. This project will utilize cellular, biochemical and genetic approaches in a simple model organism to understand how cells respond to aberrant signaling; the findings will benefit researchers working in organisms ranging from yeast to humans. In particular, they will provide valuable information on the interconnectedness of signaling and regulatory pathways downstream of receptors. In addition, novel mechanisms used by cells to compensate for mis-regulated signaling may be revealed. Broader Impact Graduate students and undergraduates, including women and minority students, will participate in these studies. The University at Buffalo (UB) is a very diverse campus, providing a great opportunity to mentor minority students. Funds from this grant will support a summer stipend for an undergraduate from a Liberal Arts College that does not itself have undergraduate research. Providing early exposure to hypothesis-driven research is essential for preparing students for careers in the biological sciences. Students will present their findings at local (monthly), regional and international meetings. Importantly, the annual C. elegans meetings foster the development of junior scientists because many of the speakers are selected from graduate student submitted abstracts. Findings from this work will also be included in the lectures in an undergraduate Signal Transduction course at UB. Mutants obtained from the genetic screens in this project will be deposited at the Caenorhabditis Genetics Center, which will distribute them to any investigator that requests them. New gene and phenotype descriptions will also be incorporated into Wormbase, an online open access resource.