Project 2 - Genetic analysis of ethanol-related behavior in Drosophila

项目摘要-项目2 酒精使用障碍（AUD）给社会带来了巨大的负担，影响深远的健康 后果影响酒精相关行为的新基因和遗传途径的鉴定 将促进AUD新治疗干预措施的开发。在这个项目中，我的实验室将使用 果蝇（果蝇）模型研究基因和遗传途径，有新的影响， 酒精相关行为该项目的分子遗传信息最终将导致更好的 人类AUD的诊断、风险确定和治疗。 该项目的一个主要重点是探索MADS盒转录因子Mef 2家族在以下方面的作用： 酒精相关行为我们的初步研究表明MEF 2家族成员参与了主观反应， 对乙醇（SRE）在人类中的作用，也表明唯一的果蝇直系同源物Mef 2是正常乙醇所必需的。 镇静剂我们的数据表明，人类乙醇镇静作用的改变可能是SRE变化的基础， 镇静和SRE的变化可能由MEF 2基因的遗传变异驱动。我们的研究结果还 支持这一假设，即对Mef 2基因家族的深入了解可能会导致重要的 关于对乙醇、SRE和潜在AUD的行为反应的见解。 该项目的另一个重点是继续使用苍蝇作为实验平台， 研究我们的生物信息学优先考虑的其他候选基因在乙醇行为中的作用， 分析核心和/或涉及其他中心项目的研究。鉴于我们对克利克的研究取得了成功 Ryanodine受体和Mef 2，我们将进一步投资于这种跨物种的方法，探索保守的 果蝇乙醇相关行为的基因和途径， 人类

Project Summary – Project 2 Alcohol use disorder (AUD) imposes a substantial burden on society with far-reaching health consequences. The identification of novel genes and genetic pathways that influence alcohol-related behaviors will facilitate the development of new therapeutic interventions for AUD. In this project my laboratory will use the Drosophila (fruit fly) model to investigate genes and genetic pathways that have novel influences on ethanol-related behavior. Molecular-genetic information from this project should ultimately lead to better diagnosis, risk determination and treatment of AUD in humans. A major focus for this project will be to explore the role of the MADS-box transcription factor Mef2 family in ethanol-related behavior. Our preliminary studies implicate a MEF2 family member in the subjective response to ethanol (SRE) in humans and also show that the sole fly ortholog Mef2 is required for normal ethanol sedation. Our data suggest that altered ethanol sedation in humans might underlie changes in SRE and that changes in both sedation and SRE might be driven by genetic variance in MEF2 genes. Our results also support the hypothesis that a deeper understanding of the Mef2 family of genes could lead to important insights regarding behavioral responses to ethanol, SRE and potentially AUD. Another major focus of this project will be to continue using the fly as an experimental platform for investigating the role of other candidate genes in ethanol behavior prioritized by our Bioinformatics and Analysis Core and/or implicated by studies in other Center Projects. Given our success with studies on Clic, the ryanodine receptor and Mef2, we will further invest in this cross-species approach for exploring conserved genes and pathways underlying ethanol-related behaviors in flies and multiple aspects of alcohol abuse in humans.