Center for Alcohol Research in Epigenetics

项目总结： P50申请的行政核心是“表观遗传学酒精研究中心(CARE)” 协调多个研究和试点项目以及表观遗传学和行为核心，包括 多学科研究团队。CARE的目标是评估乙醇诱导的表观遗传机制 (组蛋白修饰和DNA甲基化/去甲基化)转录和表位转录(RNA) 在酒精使用障碍(AUD)的发展过程中，特定的大脑回路发生了变化。这个 总体假设是乙醇引起染色质重塑(组蛋白和DNA)的转录改变 化学修饰)在特定的神经回路中，这些驱动包括焦虑的行为表型， 抑郁、动力和酒精摄入量增加。为了检验这一假设，我们选择了四个相互关联的 关于表观遗传学和表观转录组学的研究项目和两个试点项目，并建立两个资源核心，即， 利用酒精依赖大鼠模型和人死后大脑的表观遗传学和行为核心 在AUD中发现表观基因组的整合和功能方面。我们的方法考虑到 酒精对AUD的启动和维持既有积极作用也有消极作用。研究 项目#1、#2、#3和#4将评估表观基因组的状态及其在改变的转录组中的作用。 腹侧被盖区(VTA)、杏仁核、海马体和前额叶皮质(PFC)。我们将对这些进行研究 与酒精依赖的愉悦和烦躁(消极情绪状态)方面和 戒烟。我们还提出了两个试点项目；一个是关于酒精引起的外周细胞表观遗传学变化 在人类和啮齿动物中，作为积极饮酒和禁欲的生物标志物。第二个试点项目将 检查AUD中表位转换组的新区域。行政核心将提供行政管理 领导、全面管理和监督，以增强我们对基因组和 AUD的表观基因组基础。该核心还将在CARE范围内管理社区外展和培训计划。 总体而言，行政核心将保持一个富有成效和互动的环境，以加强表观遗传 澳元研究。这一多学科的努力将帮助我们确定新的治疗分子靶点 防治AUD。 好了！

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. !