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

MAOA 基因作为转化行为研究模块的表观遗传状态

• 批准号: 7787523
• 负责人: Elena Shumay
• 金额: $ 18.81万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7787523
• 关键词: Address; Affect; Aggressive behavior; Alcoholism; Animals; Area; Arousal; Arts; Attention deficit hyperactivity disorder; Behavior; Behavior Disorders; Behavioral; Behavioral Research; Biochemical; Biological; Biology; Brain; Brain Chemistry; Brain Diseases; Brain imaging; Clinical; Clinical Research; Complement; CpG Islands; DNA; DNA Sequence; Data; Development; Emotional; Environment; Epigenetic Process; Foundations; Gene Expression; Genes; Genetic; Genetic Polymorphism; Genotype; Goals; Home environment; Human; Impulsivity; Individual; Individual Differences; Intervention; Knowledge; Laboratories; Life; Link; Maps; Measurement; Measures; Mentors; Methylation; Molecular; Monoamine Oxidase A; Motivation; Neurobiology; Neurosciences; Nucleic Acid Regulatory Sequences; Participant; Patient Self-Report; Pattern; Personality; Personality Traits; Phenotype; Play; Positron; Positron-Emission Tomography; Promoter Regions; Proteins; Questionnaires; Regulation; Reporting; Research; Research Project Grants; Research Proposals; Resolution; Rewards; Role; Sampling; Science; Scientist; Technology; Testing; Training; Training Programs; Transcriptional Regulation; Variant; addiction; brain behavior; career; environmental stressor; experience; experimental analysis; human subject; improved; neurochemistry; neurogenetics; neuroimaging; pre-clinical; promoter; skills; trait

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.

描述（由申请人提供）：本申请描述了一个为期 5 年的系统培训计划，旨在开展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背后的生物机制，特别是更好地了解个体差异在遗传和表观遗传构成中的作用。为了实现这一目标，我们制定了严格的培训计划，整合了根据候选人的目标、技能和经验定制的教学和研究部分。布鲁克海文国家实验室 (BNL) 提供了完成此培训的 IC 环境 - 它是最先进的功能神经影像技术的所在地，该项目的导师是各自领域的杰出科学家和杰出专家。本提案的研究项目为实现这一目标提供了切实可行的手段。它旨在研究（提案的重点是单胺氧化酶 A (MAOA) 基因）影响大脑功能的机制。该研究将利用 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大脑中的 MAOA 活动。 PET 数据将补充高分辨率表观遗传分析。本研究提案的总体目标是研究表观遗传机制个体差异对大脑化学的贡献，从总体上了解不同行为表型背后的神经生物学基础。我们假设表观遗传机制在 MAOA 基因的转录调控中发挥重要作用，这可能导致人类行为的变化。为了测试这一点，我们建议询问基因甲基化并确定一组正常个体的甲基化变异。后续个体的甲基化模式将与其测量 MAOA 数量的大脑成像数据相关联。acti 数据将用于确定 MAOA 基因的甲基化与大脑中的数量之间是否存在相关性。该研究将通过解决脑科学中一个未解决的关键问题来添加新信息：人类行为的基础是什么和生化底物？对此表观遗传调控的验证知识提高了我们对 MAOA 基因的总体理解。 基因和环境之间的相互作用，因此添加了新的ins大脑生物学。该项目的主要目标是为候选人提供在神经科学领域（特别是神经影像学和表观遗传学）独立职业生涯所需的培训。为了实现这一目标，学员将获得有价值的科学数据，并为我们对调节大脑神经化学的机制的理解做出重大贡献，从而为越来越多的关于大脑神经化学之间关系的报告增加生化相关性。 MAOA 基因型、环境压力源和行为。 在此 K01 申请中，候选人提出了一项脑成像和遗传学方面的培训计划，以研究影响奖赏、唤醒和动机相关基因的表达，总体目标是为独立职业奠定科学和技术基础，以促进对基因-大脑-行为关系的理解，并开发对成瘾、肥胖攻击等脑部疾病的预防和干预措施。