Genetics of Ethanol-Related Behavior in Drosophila

Mike Grotewiel

Identifying gene networks that influence alcohol-related behaviors will facilitate the development of new therapeutic interventions for alcohol use disorder. We will use the Drosophila (fruit fly) model in this Project to investigate gene networks in behavioral responses to acute ethanol. There is excellent evidence from humans and rodents that behavioral responses to acute ethanol correlate with alcohol abuse or ethanol drinking, respectively. In this Project we will focus on the genetics of a robust behavioral response to acute alcohol, sedation sensitivity. In Aim 1 of this Project, we will use the Drosophila model to rapidly determine the effects of nervous system-specific RNAi-mediated knockdown of genes within several gene networks on ethanol sedation sensitivity. In Aim 2, we will expand these analyses through classical genetic studies that will formally map altered ethanol sensitivity to individual genes, determine whether the genes within each network function in concert, and determine whether each network regulates acute physiological or developmental processes that affect ethanol sedation sensitivity. In Aim 3, we will extend the genetic information from our Drosophila studies into other species, principally rodents and humans, but also C. elegans as warranted. Furthermore, we will use information from other model organism and human studies within our Center to enhance and refine the gene networks for more in-depth genetic analyses in flies. The deliberate cross-species integration built into this Project and our Center as a whole will drive a vigorous, synergistic genetic investigation of conserved gene networks underlying ethanol-related behavior.