Pilot Project

试点项目

• 批准号: 7674968
• 负责人: MICHAEL S. GROTEWIEL
• 金额: $ 7.8万
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7674968
• 关键词: Acute; Alcohol dependence; Alleles; Amino Acid Sequence; Behavior; Behavioral; Candidate Disease Gene; Diagnosis; Disease; Drosophila genus; Drug Kinetics; Ethanol; Ethanol Metabolism; GABA Receptor; Genes; Genetic; Glean; Human; Laboratories; Lead; Measures; Modeling; Molecular; Molecular Genetics; Mus; Mutation; Pathway interactions; Pharmacodynamics; Pilot Projects; Proteins; Risk; Role; Tertiary Protein Structure; Work; alcohol behavior; alcohol effect; alcohol research; alcohol response; alcohol sensitivity; base; fly; genetic analysis; mutant; novel

One of the major challenges in ethanol research is to identify conserved genetic mechanisms that influence the effects of ethanol on behavior. Integrated molecular studies in mice and humans in conjunction with preliminary genetic analyses in my lab indicate that the Drosophila model is well suited for identifying conserved genes underlying ethanol behavior. In this pilot project we will expand on our preliminary work by exploiting the Drosophila model to evaluate several candidate loci for their impact on locomotor behavior in the presence of ethanol. All of the candidate genes we will investigate are good orthologues of mouse and human genes based on primary amino acid sequence and presence of conserved protein domains. In Aim 1 we will assess the role of multiple candidate genes in ethanol sensitivity. In Aim 2, we will determine whether these candidate genes influence ethanol tolerance. In both Aims, we will explore additional candidate genes that work in concert with loci that influence ethanol sensitivity or tolerance. The planned pilot project is a key step forward in using the Drosophila model to identify conserved genetic mechanisms underlying ethanol behavior.

乙醇研究的主要挑战之一是确定影响乙醇产量的保守遗传机制。 酒精对行为的影响小鼠和人类的综合分子研究， 我实验室的初步遗传分析表明，果蝇模型非常适合识别 乙醇行为背后的保守基因在这个试点项目中，我们将扩大我们的初步工作， 利用果蝇模型评估几个候选基因座对运动行为的影响， 乙醇的存在。我们将研究的所有候选基因都是小鼠的良好直系同源物， 基于一级氨基酸序列和保守蛋白质结构域的存在的人类基因。目标1 我们将评估多个候选基因在乙醇敏感性中的作用。在目标2中，我们将确定 这些候选基因是否影响乙醇耐受性。在这两个目标中，我们将探索更多的 与影响乙醇敏感性或耐受性的基因座协同工作的候选基因。计划 在利用果蝇模型鉴定保守的遗传机制方面，一个试点项目是向前迈出的关键一步 基本的乙醇行为。