Pilot Project Core

项目概要/摘要试点项目核心 成瘾系统神经遗传学中心（CSNA）将提供试点项目的机会，以支持 发展未来的CSNA附属项目。试点项目将为新的 研究人员将为未来的成瘾系统遗传学研究提供关键的初步数据， 建立了研究人员来测试新的假设，并将他们的研究转移到使用新的小鼠 评估生物行为成瘾风险的遗传平台。在项目的初始阶段，我们 选择了三个试点项目。第一种方法利用CC/DO近交系中惊人的遗传多样性 创始人测试最近通过QTL发现的新可卡因致敏数量性状基因的修饰剂 分析密切相关的小鼠品系，Cyfip 2，并利用CSNA行为表型核心， 将这种多态性的影响从可卡因致敏性外推到药物自我给药的行为 范例第二个试点项目来自一位成熟的人类遗传学家。这是一个翻译 遗传学项目，旨在模拟和表征甲基苯丙胺使用相关的变异发现， 人类成瘾基因研究候选变体将被工程化到实验室小鼠中， BAC转基因策略。这些诱导的变体将通过一系列的行为和 分子实验第三个试点项目将整合CSNA的转录组学和遗传学， 通过评价可卡因治疗小鼠和对照小鼠的开放染色质， CC/DO创始菌株。未来的试点项目将从成瘾研究的公开征集中选出 社区，并将由内部咨询委员会与外部咨询委员会协商后选出 通过由行政核心协调的程序。项目的标准包括总体影响， 创新、研究者、CSNA内的方法和可行性、对中心的意义和相关性， 以及发展成中心附属的资助项目的可能性。

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.