Cross Species Characterization of Gene Networks in Acute Responses to Ethanol

乙醇急性反应基因网络的跨物种表征

• 批准号: 7547640
• 负责人: KENNETH SEEDMAN KENDLER
• 金额: $ 57.59万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7547640
• 关键词: Cross; Species; Characterization; Gene; Networks

DESCRIPTION (provided by applicant): The challenges and goals for the next phase of genetic research on alcohol dependence (AD) will be to i) confirm candidate genes, ii) to understand the mechanism(s) of action for individual genes in AD and iii) to use the molecular and genetic information to identify potential targets for novel interventions in AD. As a strategy to approach these complex goals, we have formulated three major organizing hypotheses that integrate and direct the individual components of this Developmental (P20) application. These include: 1. A focus on gene networks rather than individual genes which will provide mechanistic information, target identification and cross-species validation of molecular events affecting alcohol-related behaviors and risk for AD. 2. A bi-directional cross-species gene discovery and validation scheme that can provide both powerful confirmation of candidate genes and mechanistic information. Our planned studies in mice (Project 1), humans (Project 2, Pilot 2), C. elegans (Project 3), and D. melanogaster (Pilot 1) will be mutually reinforcing. 3. Initial sensitivity and acute tolerance to ethanol are phenotypes with broad cross-species experimental applicability and validated relevance to AD. For this project, for which we request four years of support, we outline a series of three developmental and two pilot projects which form a highly integrated and novel approach that implement the hypotheses outlined above. An Administrative Core and Bioinformatics Core will provide needed support across projects. The Specific Aims of individual projects will include developmental aspects that seek to broaden our scientific base, increase integration between Center components and extend our experimental models to eventually include additional behavioral phenotypes such as acute and chronic tolerance and dependence. We expect novel contributions to the field of alcohol research from our cross-species analysis of acute ethanol effects.

描述(申请人提供)：下一阶段酒精依赖(AD)遗传学研究的挑战和目标将是：i)确定候选基因，ii)了解单个基因在AD中的作用机制(S)，iii)使用分子和遗传信息来确定新的AD干预措施的潜在靶点。作为实现这些复杂目标的策略，我们制定了三个主要的组织假设，以整合和指导这一发展性(第20页)应用程序的各个组件。这些措施包括：1.关注基因网络而不是单个基因，这将提供影响酒精相关行为和AD风险的分子事件的机械性信息、目标识别和跨物种验证。2.提出了一种双向的跨物种基因发现和验证方案，该方案既能提供对候选基因的有力确认，又能提供机制信息。我们计划在小鼠(项目1)、人类(项目2、试点2)、线虫(项目3)和黑腹毛虫(试点1)上进行的研究将是相辅相成的。3.对乙醇的初始敏感性和急性耐受性是具有广泛的跨物种实验适用性的表型，并已被证实与AD相关。对于这个我们要求四年支持的项目，我们概述了一系列三个发展项目和两个试点项目，这些项目形成了一种落实上述假设的高度综合和新颖的方法。行政核心和生物信息学核心将提供跨项目所需的支持。个别项目的具体目标将包括发展方面，寻求扩大我们的科学基础，增加中心组件之间的集成，并扩展我们的实验模型，最终包括更多的行为表型，如急性和慢性耐受和依赖。我们期待通过我们对急性酒精效应的跨物种分析，为酒精研究领域做出新的贡献。