Alcohol use disorder (AUD) is a medical condition that affects 1 in 10 Americans aged 12 and older. Analysis of human Genome-wide association studies (GWAS) have uncovered 43 candidate genes of interest that might influence AUD related traits, in which 37 are shared in Drosophila. I propose to use the fruit fly model to test which of these genes is relevant for alcohol-related behaviors in vivo. Drosophila is a powerful system for studying the neurobiology of alcohol-related behaviors. The Kayser lab has found homologs of 37 of the 43 genes are shared in Drosophila. We aim to rapidly test the relevance of these 37 genes in flies to see if they affect alcohol behaviors, first by manipulating their expression, and then by identifying the life stage (development vs adult) in which the gene functions to impact alcohol behaviors. Through this project we seek to correlate our studies of flies with humans by understanding the genetic component of AUD that may put people at risk, and aid in diagnostic/preventative measures going forward. 

My first objective, which is done in this project, will be to manipulate the expression of the candidate genes in the flies through RNA interference (RNAi). The genes will be knocked down using the GAL4/UAS system to specifically select and observe one at a time. In this first phase, the purpose is to identify which of the 37 genes, once they are knocked down, influence fly behavior under exposure to ethanol. Using the drosophila ethanol behavioral assays I will assess changes in fly tolerance and sensitivity to the ethanol. This will allow me to isolate specific candidate genes that contribute to alcohol related behaviors in flies and assess their importance in vivo. The gene will then be further analyzed in part 2 of the project.