CAREER: Genetic Analysis of Neurotransmitter Release Mechanisms in Drosophila

职业：果蝇神经递质释放机制的遗传分析

• 批准号: 9734125
• 负责人: Leo Pallanck
• 金额: $ 47.5万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9734125&HistoricalAwards=false
• 关键词: CAREER; Genetic; Analysis; Neurotransmitter; Release

IBN 97-34125 PALLANCK. This is a CAREER award that has both a research and educational component. In his research, Dr. Pallanck will investigate the mechanisms of regulated release of neurotransmitters at neuronal synapses. He will use the powerful genetic and molecular approaches to available in the fruit fly Drosophila to define cellular and molecular mechanisms involved in this process. Neurons communicate with each other and with targets such as muscle cells with neurotransmitter signaling molecules, which are released when small vesicles inside the synaptic terminal fuse with the outer membrane of the cell. Recent biochemical work has identified candidate molecules that are involved in recruiting vesicles to the cell membrane at precise locations, promoting fusion, and allowing the vesicle to reform when cell membrane is pinched off towards the inside of the cell. Dr. Pallanck's research will ask which of these steps are carried out by which of the previously identified molecules, and whether there are components of the release apparatus that remain unidentified by the previous biochemical studies. In previous work, Dr. Pallanck and his collaborators has identified in Drosophila two different forms of one of the key candidate release molecules, N-ethylmaleimide-Sensitive Fusion protein (NSF). One goal of the current research is to test the hypothesis that multiple NSF proteins are involved in the targeting, fusion, and/or recycling of synaptic vesicles. Molecular, electrophysiological and anatomical studies as the electron microscope level will all be employed in these studies. To address the second goal, Dr. Pallanck's laboratory will carry out classical genetic screens to identify novel components of the vesicular release apparatus. The properties of neurotransmitter release appear to be similar at synapses in all animals, and to share mechanisms with the vesicular release of other substances such as hormones. Thus, the results from this study will contribute to a general understanding of this process. Dr. Pallanck's educational objective is to incorporate a research perspective into the undergraduate genetics curriculum at his university. He will be teaching the core genetics course taken by most undergraduate biology majors, and will use this forum to emphasize the experimental basis of scientific knowledge and to introduce students to current research opportunities in his department. He will also serve as undergraduate research coordinator, and will develop an undergraduate research seminar course. Through these three avenues, Dr. Pallanck will be instrumental in preparing undergraduate students for a career in research at a critical stage in their educational development.

IBN 97-34125帕兰克。这是一个职业奖，既有研究和教育的组成部分。 在他的研究中，Pallanck博士将研究神经突触中神经递质的调节释放机制。 他将使用强大的遗传和分子方法，在果蝇果蝇中定义参与这一过程的细胞和分子机制。 神经元相互之间以及与具有神经递质信号分子的靶细胞（例如肌肉细胞）进行通信，当突触末端内的小泡与细胞的外膜融合时，神经递质信号分子被释放。 最近的生物化学工作已经确定了候选分子，这些分子参与将囊泡募集到细胞膜的精确位置，促进融合，并允许囊泡在细胞膜被夹向细胞内部时改革。 Pallanck博士的研究将询问这些步骤中的哪些步骤是由先前确定的分子进行的，以及是否有释放装置的成分仍然未被先前的生化研究所确定。 在之前的工作中，Pallanck博士和他的合作者在果蝇中发现了关键候选释放分子之一N-乙基马来酰亚胺敏感融合蛋白（NSF）的两种不同形式。 目前研究的一个目标是检验多个NSF蛋白参与突触囊泡的靶向、融合和/或回收的假设。 这些研究将采用分子、电生理和解剖学等电子显微镜水平的研究。 为了实现第二个目标，Pallanck博士的实验室将进行经典的遗传筛选，以确定囊泡释放装置的新组件。 神经递质释放的性质似乎在所有动物的突触上都是相似的，并且与其他物质（如激素）的囊泡释放机制相同。 因此，这项研究的结果将有助于对这一过程的普遍理解。Pallanck博士的教育目标是将研究视角纳入他所在大学的本科遗传学课程。 他将教授大多数本科生物学专业的核心遗传学课程，并将利用这个论坛来强调科学知识的实验基础，并向学生介绍他所在部门目前的研究机会。 他还将担任本科研究协调员，并将开发本科研究研讨会课程。 通过这三个途径，博士Pallanck将有助于准备本科生在他们的教育发展的关键阶段的研究生涯。