EVOGENE / FYSCELL Joint Seminar: Rudolf Bohm - Using circuit mapping in the fruit-fly to identify disease mechanisms

Abstract: Behavior in Drosophila has been used as a lens to focus on neural function. For its part, behavioral genetics in fruit fly has led to some of the seminal discoveries of genes involved in setting up neural circuitry and allowing it to function appropriately. A short-list of these behavioral genes – dominants capitalized – identified are those that control function such as Shaker, seizure, slowpoke and cacophony; those that control basic cell biology such as period, timeless, dunce and radish; and those that control development of the circuitry needed to function: fruitless. The story of these genes and the quirky scientists who studied them was popularized by Jonathan Weiner in his award-winning book Time, Love and Memory. Here, he wrote about the descendants of Seymour Benzer – a scientist credited with starting behavioral genetics at Cal-Tech. Recently, the first group of these to get any serious attention was the "clock" people – Mike Young, Michael Rosbash and Jeff Hall – who were awarded the Nobel Prize for their work on the genetics of the circadian clock. But, from the beginning, the behavioral genetics approach was an attempt to discern function from mutations that affect behavior. Behavior being chosen here as a subtle measure of performance. My lab has extended upon this early work to come back to measurements of performance, but with a focus on diseases that cause human pathologies. In some cases, we model the disease using analogous mutations in homologous genes (calcium channel), in other cases, we use dominantly toxic human proteins that cause degeneration (Spinocerebellar Ataxia, Huntington's Disease). Our goal is to identify genes and pharmacology that can ameliorate the problems. As interest in epigenetics has peaked, I will also discuss how the approach of using behavioral genetics to study adaptation generated insight into how alcohol modifies one of these behavioral genes epigenetically (slowpoke).