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

描述（由申请人提供）：该申请描述了一个系统的5年培训计划，以启动独立的神经科学研究职业，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理解大脑功能的生物学机制，特别是更好地理解遗传和表观遗传组成中个体变异的作用。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适合候选人的目标，技能和经验放在一起。布鲁克海文国家实验室（BNL）提供了一个IC环境来完成这项培训-它是最先进的功能性神经成像技术的家园，该项目的导师是杰出的科学家，在各自领域的杰出专家。本研究项目的建议书是实现这一目标的现实手段。其目的是研究影响脑功能的机制（该提案的重点是单胺氧化酶A（MAOA）基因）。该研究将利用BNL提供的独特机会：正电子发射断层扫描仪可以直接测量活体人脑中的MAOA活动。PET数据将通过高分辨率表观遗传分析得到补充。这项研究的总体目标是调查脑化学中表观遗传机制个体差异的贡献，以全面了解不同行为表型的神经生物学基础。我们推测，表观遗传机制在MAOA基因的转录调控中起重要作用，这可能有助于人类行为的变化。为了测试这一点，我们建议interroga基因甲基化，并确定在一组正常人的甲基化的变化。随后个体的甲基化模式将与他们的脑成像数据相关联，测量MAOA活性的量，数据将用于确定MAOA基因的甲基化与脑中的量之间是否存在相关性。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：人类行为的基础是什么？对表观遗传调控的验证知识提高了我们对基因和环境之间相互作用的一般理解，因此增加了一个新的大脑生物学。该项目的主要目标是提供候选人在神经科学，特别是神经影像学和表观遗传学方面开始独立职业生涯所需的培训。追求这一目标，受训者将获得有价值的科学数据，并显着有助于我们的大脑神经化学调节机制的理解，从而增加了越来越多的单胺氧化酶基因型，环境压力和行为之间的关系的报告的生化相关性。 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，以研究影响奖励，唤醒和动机的基因表达的总体目标，为独立职业生涯奠定科学和技术基础，以促进对基因-大脑-行为关系的理解，以及预防和干预大脑疾病的发展，如成瘾，出窍攻击。

DESCRIPTION (provided by applicant): This application describes a systematic 5-years training plan to launch an independent research career 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 an IC 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. 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-behavior relationships and the development of preventions and interventions for brain disorders such as addiction, obe aggression.