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: 8442944
• 负责人: Elena Shumay
• 金额: $ 2.81万
• 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 2013-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8442944
• 关键词: Address; Affect; Aggressive behavior; Alcoholism; Animals; Area; Arousal; 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; Instruction; 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; Preventive Intervention; 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; career; environmental stressor; experience; experimental analysis; human subject; improved; neurochemistry; neurogenetics; neuroimaging; preclinical study; promoter; skills; trait

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.

本申请描述了一项系统的5年培训计划，以启动独立研究项目 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 有助于理解大脑功能的生物学机制，特别是更好地 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，严格的培训计划，整合教学和研究部分，量身定做 应聘者的目标、技能和经验被放在一起。布鲁克海文国家实验室(BNL)提供ANIC 完成这项训练的环境-它是最先进的功能神经成像技术的发源地 该项目的导师是杰出的科学家和各自领域的杰出专家。的研究项目。 建议落实了实现这一目标的实际手段。它的目的是调查通过什么机制 (该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 能够直接测量活着的人脑中的MAOA活动。宠物数据将得到补充 高分辨率表观遗传学分析。 这项研究计划的总体目标是调查表观遗传机制的贡献。 从总体上理解神经生物学底物的脑化学的个体差异 潜藏着不同的行为表型。 我们假设表观遗传机制在转录调控中起重要作用。 MAOA基因，它可能导致人类行为的变异。为了测试这一点，我们建议审问 基因甲基化，并确定一组正常个体的甲基化变异。降序列器 个体的甲基化模式将与他们测量MAO A活动量的脑成像数据联系起来 数据将被用来确定MAOA基因的甲基化与氨基酸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关键的悬而未决的问题来增加新的信息：什么 生化底物是人类行为的基础吗？证实了对此的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一般理解，因此增加一个新的INS 脑生物学。 该项目的主要目标是提供候选人开始独立职业生涯所需的培训 在神经科学，特别是在神经成像和表观遗传学方面。为了实现这一目标，学员将获得 有价值的科学数据，对我们理解大脑的调节机制有很大帮助 神经化学，因此增加了生化相关性，越来越多的报告之间的关系 MAOA基因、环境应激源和行为。 相关性(请参阅说明)： 在这份K01申请中，应聘者向学生提出了一项脑成像和遗传学方面的培训计划 影响奖赏、唤醒和激励相关基因的表达，主要目标是 促进基因-脑行为理解的独立事业的科学和技术基础 成瘾、脱体等脑部疾病的关系及预防和干预研究进展 攻击性。