Project Summary: The Administrative Core of the P50 application on “Center for Alcohol Research in Epigenetics (CARE)” will coordinate multiple research and pilot projects and the Epigenetics and Behavioral Cores comprising of multidisciplinary research teams. The goal of the CARE to evaluate ethanol-induced epigenetic mechanisms (histone modifications and DNA methylation/demethylation) of transcriptomic and epitranscriptomic (RNA modifications) changes in specific brain circuitries during the development of alcohol use disorder (AUD). The overall hypothesis is that ethanol induces transcriptomic changes due to chromatin remodeling (histone & DNA chemical modifications) in specific neurocircuitries, and that these drive behavioral phenotypes including anxiety, depression, motivation, and escalated ethanol intake. To test this hypothesis, we have selected four interrelated research projects and two pilot projects on epigenetics and epitranscriptomics and set-up two resource cores i.e., Epigenetics and Behavioral Cores utilizing a rat model of alcohol dependence and human postmortem brains to discover integrated and functional facets of the epigenome in AUD. Our approach takes into consideration that both negative and positive effects of ethanol contribute to the initiation and maintenance of AUD. Research projects #1, #2, #3 and #4 will evaluate the status of the epigenome and its role in the altered transcriptome in the ventral tegmental area (VTA), amygdala, hippocampus, and prefrontal cortex (PFC). We will examine these in relation to both the euphoric and dysphoric (negative emotional state) aspects of ethanol dependence and withdrawal. We also propose two pilot projects; one on ethanol-induced epigenetic changes in peripheral cells in humans and rodents serving as biomarkers of active drinking and abstinence. A second pilot project will examine the novel area of the epitranscritome in AUD. The Administrative Core will provide administrative leadership, overall management, and oversight in order to enhance our understanding of the genomic and epigenomic basis of AUD. This Core will also manage community outreach and training programs within CARE. Overall, the Administrative Core will maintain a productive and interactive environment to enhance epigenetic research in AUD. This multidisciplinary endeavor will help us identify novel therapeutic molecular targets to prevent and treat AUD. !