Center for Systems Neurogenetics of Addiction

成瘾系统神经遗传学中心

基本信息

批准号：
9151757
负责人：
Elissa J Chesler
金额：
$ 258.71万
依托单位：
JACKSON LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-15 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9151757
关键词：
Accounting Acute Adolescent Adopted Affect Awareness Behavior Behavioral Behavioral Genetics Bioinformatics Biological Biological Factors Chromosome Mapping Circadian Dysregulation Circadian Rhythms Cocaine Cocaine Dependence Collaborations Communities Complex Computing Methodologies Core Facility Data Data Analyses Data Set Dependence Deposition Development Diagnostic Disease Drug Addiction Drug Exposure Drug abuse Drug usage Early Intervention Early treatment Education Environment Exhibits Family Fostering Funding Future Gene Expression Profiling Gene Targeting Genes Genetic Genetic Crosses Genetic Variation Genetic study Genomics Genotype Goals Human Human Genetics Impulsivity In Vitro Individual Individual Differences Informatics Institution Intervention Knowledge Laboratories Laboratory mice Lead Link Maps Methodology Mission Modeling Molecular Genetics Molecular Profiling Mus Mutant Strains Mice Mutation Neurosciences Research Nicotine Pathway interactions Pattern Pharmaceutical Preparations Phenotype Population Population Genetics Population Heterogeneity Predisposition Prevention Preventive measure Public Health Quantitative Trait Loci Research Research Activity Research Personnel Research Support Resource Informatics Resources Rewards Risk Risk Factors Sampling Self Administration Self-Administered Services Source Staging Structure Substance Use Disorder System Techniques Testing The Jackson Laboratory Therapeutic Training Validation Variant Work addiction base behavioral study biobank biobehavior cost experience functional genomics genetic analysis genetic variant genome editing holistic approach illicit drug use in vivo in vivo Model innovative technologies insight model development mouse model neurobehavioral neurobiological mechanism neurogenetics novel novel strategies phenomics prevent programs psychostimulant relating to nervous system response sex stimulant abuse symposium tool trait

项目摘要

PROJECT SUMMARY OVERALL COMPONENT The Center for Systems Neurogenetics of Addiction (CSNA) synergizes the expertise and effort of behavioral neuroscientists, computational biologists and geneticists, who each bring state-of-the-art approaches to an integrated research program that will identify and model the common underlying biological mechanisms of biobehavioral risks for stimulant self-administration. Drug addiction is a devastating and highly complex neurobehavioral phenomenon, characterized by multiple etiological factors, stages and behaviors that have proven difficult to study in combination. Advanced mouse genetic populations provide a platform for evaluating the relationships among these behaviors, finding genetic variants responsible for their variation and identifying their associated biological mechanisms and pathways. We will make use of the new Collaborative Cross genetic reference population and Diversity Outbred mapping population to identify the biological mechanisms by which predisposing traits predict the tendency to self-administer the psychostimulant drug cocaine. Each predisposing trait, including impulsivity, acute and sensitized drug responses, reward-seeking, adolescent nicotine exposure and circadian variation, is studied in one of the Center's five scientific projects. Our approach is unprecedented in that we will evaluate these traits simultaneously in a mouse population exhibiting extreme genetic and phenotypic variation, enabling a holistic and extensible assessment of the common and distinct biological mechanisms of addiction vulnerability. We will definitively and directly identify sources of trait correlation in the population. We will produce functional genomics and phenomics datasets, which will be deposited in widely accessed and highly functional informatics resources, where they may be expanded upon by the global research community. Our Center will also generate novel, validated mouse mutants and complex models for mechanistic studies of addiction-related phenomena. In addition to aiding the scientific mission of our five scientific projects, our three research support cores will provide proven, state-of-the-art and innovative technologies to the broader field, including: 1) a sophisticated, large-capacity Behavioral Phenotyping Core, 2) an Integrative Genetics and Genomics Core for statistical genetics, molecular profiling, biobanking and data dissemination, and 3) a Mouse Resource and Validation Core for delivering novel mouse resources for systems genetics, in vitro and in vivo mutation induction and validation. The Administrative Core will oversee the effective coordination, integration and dissemination of the Center's research activities and deliver our findings through The Jackson Laboratory (JAX)'s well-established educational programs. The Pilot Core will offer additional investigators the opportunity to initiate collaborative work with the Center. Through its combined efforts, the CSNA will enable discovery of the mechanisms linking multiple susceptibility phenotypes to the propensity to seek and take drugs, opening up new opportunities for both prevention in those at risk for addiction and intervention in those already afflicted.

项目摘要整体组件系统神经源性成瘾中心（CSNA）协同行为的专业知识和努力神经科学家，计算生物学家和遗传学家，他们每个人都将最先进的方法带入综合研究计划，该计划将识别和建模刺激自我管理的生物行为风险。吸毒成瘾是一种毁灭性且高度复杂的神经行为现象，其特征是多种病因，阶段和行为的特征被证明很难结合研究。高级小鼠遗传种群提供了一个评估的平台这些行为之间的关系，找到负责其变异的遗传变异并识别它们相关的生物学机制和途径。我们将利用新的合作十字架遗传参考人群和多样性繁殖地图种群，以识别生物学机制易感性的特征预测了自我管理心理刺激药物可卡因的趋势。每个诱发性状，包括冲动性，急性和敏感药物反应，寻求奖励，青少年尼古丁的暴露和昼夜节律变化是在该中心的五个科学项目之一中研究的。我们的方法没有前所未有遗传和表型变异，可以对常见和独特的全面评估进行整体评估成瘾脆弱性的生物学机制。我们将明确，直接确定特征的来源人口的相关性。我们将生成功能性基因组学和现象学数据集，这将是存放在广泛访问和高度功能的信息学资源中，可以在其中扩展由全球研究界。我们的中心还将产生新颖的，经过验证的小鼠突变体和复合体与成瘾相关现象的机械研究模型。除了协助科学任务我们的五个科学项目，我们的三个研究支持核心将提供经过验证的，最先进的创新性更广泛领域的技术，包括：1）复杂的大能力行为表型核心，2）用于统计遗传学，分子分析，生物群和数据的综合遗传学和基因组学核心传播，以及3）鼠标资源和验证核心，用于提供新的鼠标资源系统遗传学，体外和体内突变诱导和验证。行政核心将监督中心研究活动的有效协调，整合和传播，并提供我们的通过杰克逊实验室（JAX）的成就良好的教育计划的发现。飞行员核心将为其他调查人员提供与中心合作工作的机会。通过它的结合努力，CSNA将使能够发现将多个敏感性表型与该机制联系起来的机制寻求和服用毒品的倾向，为那些有风险的人打开了新的预防机会成瘾和干预已经折磨的人。