Pilot Project Core

项目摘要/摘要试点项目核心 成瘾系统神经遗传学中心(CSNA)将提供试点项目机会，以支持 未来CSNA附属项目的发展。试点项目将为新的 调查人员将为未来成瘾的系统遗传学研究产生关键的初步数据，并将使 已建立的研究人员将测试新的假设并将他们的研究移植到新老鼠的使用上 用于评估生物行为成瘾风险的遗传平台。在该计划的初始阶段，我们 选择了三个试点项目。第一种利用了CC/DO近交系中惊人的遗传多样性 创始人测试QTL最近发现的一个新的可卡因致敏数量性状基因的修饰物 分析亲缘关系密切的小鼠品系Cyfip2，并利用CSNA行为表型核心 从可卡因敏化到药物自我给药行为的这种多态效应外推 范例。第二个试点项目来自一位著名的人类遗传学家。这是一个翻译版本 遗传学项目，旨在模拟和表征在 关于成瘾的人类遗传学研究。候选变种将被改造成实验室小鼠，使用 BAC转基因策略。这些诱导变种将通过一系列行为和 分子实验。第三个试点项目将使CSNA的转录和基因 通过评估可卡因处理组和对照组小鼠开放染色质的表观遗传学分析发现 CC/DO方正菌株。未来的试点项目将从公开征集到成瘾研究 并将由内部咨询委员会与外部咨询委员会协商选定 通过一个由行政核心协调的进程。项目的标准包括总体影响， CSNA内的创新、调查者、方法和可行性，对中心的意义和相关性， 并有可能发展为中心附属的、有资金支持的项目。

PROJECT SUMMARY/ABSTRACT PILOT PROJECT CORE The Center for Systems Neurogenetics of Addiction (CSNA) will offer pilot project opportunities to support the development of future CSNA-affiliated projects. Pilot projects will create critical opportunities for new investigators to generate key preliminary data for future systems genetic studies of addiction and will enable established investigators to test new hypotheses and migrate their research into the use of novel mouse genetic platforms for the assessment of biobehavioral addiction risk. In the initial phase of the program, we have selected three pilot projects. The first uses the phenomenal genetic diversity in the CC/DO inbred founders to test for modifiers of a new cocaine sensitization quantitative trait gene recently discovered by QTL analysis in closely related mouse strains, Cyfip2, and makes use of the CSNA Behavioral Phenotyping Core to extrapolate the effects of this polymorphism from cocaine sensitization to behavior in drug self-administration paradigms. The second pilot project comes from an established human geneticist. This is a translational genetics project, aimed to model and characterized methamphetamine use-related variants discovered in human genetic studies of addiction. Candidate variants will be engineered into the laboratory mouse using BAC transgenic strategies. These induced variants will be evaluated through a series of behavioral and molecular experiments. A third pilot project will enable integration of the CSNA's transcriptomic and genetic findings with epigenetic analysis by evaluating open chromatin in cocaine treated and control mice from the CC/DO founder strains. Future pilot projects will be selected from an open solicitation to the addiction research community and will be selected by the Internal Advisory Board in consultation with the External Advisory Board through a process coordinated by the Administrative Core. Criteria for the projects include overall impact, innovation, investigator, approach and feasibility within the CSNA, significance and relevance to the center, and likelihood to develop into center-affiliated, funded projects.