Repeated Binge Drinking and the Genetic Regulation of Corticostriatal Synchrony

K99/R00奖项头两年的主要目标是为候选人提供 生物信息学在脑基因表达网络识别和分析中的培训 酒精中毒的神经生理遗传学的学术研究生涯。候选人的具体目标是 该项目的K99阶段是确定招募的基因网络(以及控制这些网络的关键基因) 通过在大脑中被认为与酒精失控有关的区域反复酗酒 消耗-内侧前额叶皮质(MPFC)和腹侧纹状体(VSTR；即伏隔核)。 应聘者将接受强化训练，以获得必要的技能和专业知识 分析和解释下一代测序数据。他将通过完成以下工作来促进他的职业发展 为期一学期的下一代测序和生物信息学的教学课程，以及 参加有关成瘾遗传学、统计遗传学和网络分析的短期强化课程。他的 职业发展也将通过参加相关的研讨会和研讨会系列来进一步发展。 印第安纳大学酒精研究中心(IARC)和计算生物学和 生物信息学(CCBB)，并通过发表他的研究成果，参加科学会议，以及 面试独立教员职位。建议的指导团队包括克里斯托弗博士 Lapish、Tatiana Foroud、刘云龙和Howard Edenberg。这些人都是 系统和计算电生理学、统计和生物信息学分析以及医学/人口 基因组学和遗传学。IUPUI，特别是IARC的长期合作研究环境， 将为候选人提供必要的资源，以实现本提案中概述的目标。在 在奖项的R00阶段的第三年开始，候选人将确立他的新角色 独立的教师研究员，他将继续他的研究，识别，验证和 表征与重复过度相关的调节大脑回路的基因和基因网络 饮酒，以及这种饮酒的遗传风险。这将通过结合新的 凭借他目前在行为生理学和行为遗传学方面的专业知识，获得了生物信息学方面的技能。 确定过量饮酒的遗传和神经生理学原因及后果 与NIAAA在了解酒精中毒的神经生物学方面的使命直接相关。具体来说， 拟议中的研究将揭示基因网络的协调活动如何调节生理 一个关键的大脑奖赏回路的运作，以促进反复过量饮酒。这将导致 更好地了解饮酒为什么以及如何导致成瘾，这将帮助我们制定策略 预防和治疗过度饮酒。

The primary objective of the first two years of the K99/R00 award is to provide the candidate with bioinformatics training in the identification and analysis of brain gene expression networks in preparation for an academic research career in the neurophysiological genetics of alcoholism. The candidates specific goal for the K99 phase of the project is to identify gene networks (and key genes regulating these networks) recruited by repeated binge alcohol consumption within brain areas thought to be involved in loss of control over alcohol consumption - the medial Prefrontal Cortex (mPFC) and the ventral Striatum (vSTR; i.e. nucleus accumbens). The candidate will undertake an intensive training regimen to obtain the necessary skills and expertise to analyze and interpret next-generation sequencing data. He will further his career development by completing semester-long didactic coursework in both next-generation sequencing and bioinformatics, and also by attending intensive short courses on the genetics of addiction, statistical genetics, and network analysis. His career development will also be furthered by attending relevant seminars and seminar series offered through the Indiana University Alcohol Research Center (IARC) and Center for Computational Biology and Bioinformatics (CCBB), and by publishing his research findings, attending scientific conferences, and interviewing for independent faculty positions. The proposed mentoring team includes, Drs. Christopher Lapish, Tatiana Foroud, Yunlong Liu, and Howard Edenberg. These individuals collectively are experts in systems and computational electrophysiology, statistical and bioinformatics analyses, and medical/population genomics and genetics. The long-standing collaborative research environment at IUPUI, in particular the IARC, will provide the candidate the necessary resources to complete the aims as outlined in this proposal. At the start of the 3rd year during the R00 phase of the award, the candidate will establish his new role as an independent faculty researcher where he will continue his research on identifying, validating, and characterizing genes and gene networks regulating the brain circuits associated with repeated excessive alcohol consumption, and genetic risk for such consumption. This will be accomplished by combining newly acquired skills in bioinformatics with his current expertise in behavioral physiology and behavioral genetics. Determining the genetic and neurophysiological causes and consequences of excessive alcohol consumption are directly relevant to the mission of the NIAAA in understanding the neurobiology of alcoholism. Specifically, the proposed studies will reveal how the coordinated activity of networks of genes mediates the physiological functioning of a key brain reward circuit to facilitate repeated excessive alcohol consumption. This will result in a better understanding of why and how alcohol use leads to addiction and will help us develop strategies to prevent and treat excessive drinking.