Genetic Dissection of Synaptic Transmission

描述(由申请人提供)： 该项目的长期目标是了解突触的分子和细胞生理学，作为了解神经系统功能和功能障碍的更复杂方面的先决条件。这项研究可能会对神经生物学的许多领域产生影响，包括突触可塑性、信息处理、行为、成瘾、神经退化和精神疾病。这项研究的起点是现有的13个果蝇突变体的集合，这些突变体是根据光感受器突触传递表型确定的。具体目标包括：1)扩展表型特征，包括突触超微结构和神经肌肉电生理学；2)分子克隆与最有趣的突变体相对应的基因；3)确定相应蛋白质的分子同一性和细胞功能。这一研究职业奖的候选人R.Steven Stowers博士此前曾在Thomas Schwarz博士和Corey Goodman博士的实验室进行过突触传递的分子和遗传学研究。通过这个奖项，斯托尔斯博士将利用他推荐的导师、加州大学伯克利分校的埃胡德·伊萨科夫博士的电生理学和光学成像专业知识，更好地了解他的突触传递突变体中缺陷的本质。在将这些生物物理技术应用于神经生物学问题方面，斯托尔斯博士将获得的培训将补充他在遗传学以及分子和细胞生物学方面已经很强大的背景。此外，加州大学伯克利分校的研讨会、研讨会系列和优秀的神经科学社区提供了一个出色的神经科学培训环境。通过扩展和多样化他的技能，包括电生理学和光学成像，斯托尔斯博士将发展成为一名强大的、全面发展的神经科学家，他的理想地位既可以实现他在研究型大学获得教职的眼前职业目标，也可以实现他对神经生物学做出重大贡献的长期职业目标。

DESCRIPTION (provided by applicant): The long term objectives of this project are to understand the molecular and cellular physiology of the synapse as a prerequisite for comprehending more complex aspects of nervous system function and dysfunction. This research will likely have implications for many areas of neurobiology including synaptic plasticity, information processing, behavior, addiction, neurodegeneration, and psychiatric disease. The starting point of this research is an existing collection of 13 Drosophila mutants identified on the basis of a photoreceptor synaptic transmission phenotype. Specific aims include: 1) extending phenotypic characterization to include synapse ultrastructure and neuromuscular electrophysiology, 2) molecular cloning of the genes corresponding to the most interesting mutants, and 3) determining the molecular identity and cellular functions of the corresponding proteins. The candidate for this Research Career Award, Dr. R. Steven Stowers, has previously carried out molecular and genetic studies of synaptic transmission in the labs of Drs. Thomas Schwarz and Corey Goodman. Through this award, Dr. Stowers will take advantage of the electrophysiology and optical imaging expertise of his proposed mentor, Dr. Ehud Isacoff at UC Berkeley, to better understand the nature of the defects in his synaptic transmission mutants. The training Dr. Stowers will acquire in applying these biophysical techniques to neurobiological problems will complement his already strong background in genetics and molecular and cellular biology. In addition, the workshops, seminar series, and excellent neuroscience community at UC Berkeley provide an outstanding neuroscience training environment. Through expanding and diversifying his skill set to include electrophysiology and optical imaging, Dr. Stowers will develop into a formidable, well rounded neuroscientist ideally positioned to achieve both his immediate career goal of obtaining a faculty position at a research university and his long-term career goal of making significant contributions to neurobiology.