Center for Alcohol Research in Epigenetics

项目摘要： 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）转录组和表转录组（RNA 在酒精使用障碍（AUD）的发展过程中，特定脑回路的变化。的 总的假设是乙醇诱导由于染色质重塑（组蛋白和DNA）引起的转录组学变化 化学修饰）在特定的神经回路，这些驱动行为表型，包括焦虑， 抑郁、动力和酒精摄入量的增加。为了验证这一假设，我们选择了四个相互关联的 开展了表观遗传学和表观转录组学研究项目和两个试点项目，并建立了两个资源核心， 表观遗传学和行为核心利用酒精依赖大鼠模型和人类死后大脑， 发现AUD表观基因组的整合和功能方面。我们的做法考虑到， 乙醇的负面和正面作用都有助于AUD的启动和维持。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转录组中的作用， 腹侧被盖区（VTA）、杏仁核、海马和前额叶皮质（PFC）。我们将研究这些 与酒精依赖的欣快和烦躁（消极情绪状态）方面有关， 戒断我们还提出了两个试点项目，一个是关于乙醇诱导的外周细胞表观遗传变化 在人类和啮齿动物中作为主动饮酒和戒酒的生物标志物。第二个试点项目将 检查AUD中的表transscritome的新区域。行政核心将提供行政 领导，全面管理和监督，以提高我们对基因组和 AUD的表观基因组基础。该核心还将管理援外社内的社区外展和培训方案。 总的来说，行政核心将保持一个富有成效和互动的环境，以提高表观遗传 研究在AUD。这种多学科的奋进将帮助我们确定新的治疗分子靶点， 预防和治疗AUD。 !

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. !