Epigenetic Status of MAOA Gene as a Module of Translational Behavioral Research

本申请描述了一个系统的5年培训计划，以启动一个独立的研究事业 神经科学，重点是功能表观遗传学和脑成像。候选人的总体目标 有助于了解大脑功能的生物学机制，特别是更好地了解大脑功能。 个体变异在遗传和表观遗传构成中的作用。 为了实现这一目标，一个严格的培训计划，整合教学和研究组件量身定制， 候选人的目标，技能和经验放在一起。布鲁克海文国家实验室（BNL）提供了一种 环境来完成这项培训-这是一个家，以国家的最先进的功能神经成像技术 该项目的导师是杰出的科学家，他们是各自领域的杰出专家。研究项目 该提案实施了实现这一目标的实际手段。其目的是研究 （提案的重点是单胺氧化酶A（MAOA）基因）影响大脑功能。 这项研究将利用BNL提供的独特机会：正电子发射断层扫描仪 能够直接测量活人脑中的MAOA活性。PET数据将补充到 高分辨率表观遗传分析 这项研究的总体目标是探讨表观遗传机制的贡献 脑化学中的个体差异，以全面了解神经生物学基础 不同行为表型的基础。 我们推测，表观遗传机制在转录调控中起着重要作用。 MAOA基因可能导致人类行为的变化。为了验证这一点，我们建议询问 基因甲基化并确定一组正常个体中甲基化的变化。后续序列 个体的甲基化模式将与他们的大脑成像数据相关联，这些数据测量的是单胺氧化酶A活性的量， 数据将用于确定MAOA基因甲基化与MAOA基因突变之间是否存在相关性。 在大脑里。 这项研究将通过解决脑科学中一个尚未解决的关键问题来增加新的信息： 和生物化学基质构成了人类行为的基础验证了这种表观遗传调控的知识， 提高我们对基因和环境之间相互作用的普遍理解，因此增加一个新的基因， 脑生物学 该项目的主要目标是为候选人提供开始独立职业所需的培训 尤其是神经成像和表观遗传学。为了实现这一目标，学员将获得 有价值的科学数据，并大大有助于我们了解。调节大脑的机制， 神经化学，从而增加了生物化学的相关性越来越多的报告之间的关系， MAOA基因型、环境应激源和行为。 相关性（参见说明）： 在这个K 01申请中，候选人提出了一个脑成像和遗传学的培训计划，以学习 影响涉及奖励、唤醒和动机的基因表达，其总体目标是 科学和技术基础的独立事业，在推进理解基因-脑-神经系统 关系和发展的预防和干预大脑疾病，如成瘾， 侵略

This application describes a systematic 5-years training plan to launch an independent research caree neuroscience with emphasis on functional epigenetics and brain imaging. The overall goal of the Candidate contribute to the understanding of the biological mechanisms underlying brain function, specifically, to better i the role of individual variations in genetic and epigenetic makeup. To achieve this goal, a rigorous training plan, integrating didactic and research components tailored to candidate's goals, skills and experience is put together. Brookhaven National Laboratory (BNL) provides anic environment to accomplish this training - it is a home to state-of-the-art functional neuroimaging technologies mentors of this project are distinguished scientists, preeminent experts in their areas. The research project of proposal implements the practical mean to achieve this goal. It aims to investigate the mechanisms by which (focus of the proposal is on monoamine oxidase A (MAOA) gene) affect brain function. The research will make use of the unique opportunity afforded by BNL: Positron Emission Tomograph enables direct measurement of the MAOA activity in the living human brain. PET data will be complemented t high-resolution epigenetic analysis. The overall goal of this research proposal is to investigate the contribution of epigenetic mechanism individual differences in brain chemistry with an overarching view to understand the neurobiological substrate underlying different behavioral phenotypes. We hypothesize that epigenetic mechanisms play an important role in the transcriptional regulation o MAOA gene which potentially contribute to variation in human behavior. To test this, we propose to interroga gene methylation and determine the variation in methylation across a group of normal individuals. Subsequer individual's methylation pattern will be linked to their brain imaging data measuring the amount of MAO A acti data will be(used to determine if there is a correlation between methylation of the MAOA gene and the amoun in the brain. The study will add new information by addressing a key unresolved question in brain science: What and biochemical-substrates underlie human behavior? Verified knowledge of the epigenetic regulation of this improve our general understanding of the interplay between genes and the environment, so adding a new ins brain biology. The project's main objective is to afford training needed for the candidate to initiate an independent career in neuroscience, particularly in neuroimaging and epigenetics. Pursuing this objective, the trainee will obtain valuable scientific data and significantly contribute to our understanding of.the mechanisms regulating brain neurochemistry, thus add biochemical relevance to the growing number of reports of relationships between the MAOA genotype, environmental stressors and behavior. RELEVANCE (See instructions): In this K01 application the candidate proposes a training program in brain imaging and genetics to stu affecting the expression of the genes involved in reward, arousal and motivation with the overarching goal to scientific and technical foundation for an independent career in advancing understanding of gene-brain-behav relationships and the development of preventions and interventions for brain disorders such as addiction, obe aggression.