A versatile system for cell-specific control of gene expression in the fly brain

果蝇大脑中细胞特异性基因表达控制的多功能系统

• 批准号: 8662893
• 负责人: Thomas Robert Clandinin
• 金额: $ 27.23万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8662893
• 关键词: Address; Adult; Aging; Animal Model; Brain; Brain region; Bypass; Cells; Collection; Communities; Confocal Microscopy; Controlled Vocabulary; DNA Sequence; Data; Databases; Development; Disease; Drosophila genus; Elements; Enhancers; Functional disorder; Future; Gene Expression; Genes; Genetic; Genetic Crosses; Genetic Models; Genome; Health; Individual; Inherited; Label; Learning; Maps; Memory; Methods; Modeling; Molecular; Nerve Degeneration; Nervous System Physiology; Nervous system structure; Neurons; Neurophysiology - biologic function; Neurosciences; Pattern; Preclinical Drug Evaluation; Process; Regulatory Element; Reporter; Research Personnel; Resolution; Resources; Seeds; Site; Specificity; Staging; Structure; System; Target Populations; Technology; Testing; Time; Transgenic Organisms; Visual system structure; Work; base; brain cell; cell type; cost; cost effective; design; field study; flexibility; fly; gene discovery; innovation; insight; interest; nervous system disorder; neural circuit; relating to nervous system; repaired; research study; somatosensory; tool; transcription factor

DESCRIPTION (provided by applicant): Modern neuroscience seeks to identify, and manipulate with precision, specific cell types in the brain to identify mechanisms of circuit assembly, function, and neural disease. These technologies are a prerequisite to a large number of fields of study, from systems neuroscience to molecular developmental analysis, and are key to providing insights not only into neural function, but also disease processes, including aging, neurodegeneration, and neural repair developing tools to label and manipulate specific neuronal types is generally costly and time-consuming. The objective of this application is to develop and release to the scientific community an extensive and versatile toolkit for manipulation of the nervous system of Drosophila, a powerful genetic model that has generated many fundamental insights into nervous system function and development. This application has three central aims. First, we propose to generate 4,000 new transgenic lines based on the recently developed InSITE system. These strains will allow cell-specific manipulations of gene expression in the vast majority of neurons in the fly. Each of these insertion sites will be molecularly mapped, and the expression pattern captured by each line will be described in both larval and adult fly brains. Second, using this collection, we will derive cell-type specific intersectional tools, as well as independent transcriptional regulatory systems, allowing gene expression to be manipulated in multiple individual cell types, independently. Third, we will create a database describing these data that will enable the community to make full use of this resource to address a wide range of scientific questions. This collection will provide a platform for introducing a versatile collection of markers and drivers of gene expression into a large number of the neuronal types present in the larval and adult nervous systems for release to the Drosophila community. Once this resource is established, the methods for using and extending the collection involve only basic genetic crosses that can be adapted in any lab. We expect that this collection will seed an expanding, highly versatile, and cost-effective collection of tools fo manipulation of the nervous system and gene discovery.

描述（由申请人提供）：现代神经科学致力于识别和精确操作大脑中的特定细胞类型，以识别电路组装、功能和神经疾病的机制。这些技术是从系统神经科学到分子发育分析等许多研究领域的先决条件，并且不仅是提供对神经功能以及疾病过程（包括衰老、神经退行性变和神经修复）见解的关键，开发用于标记和操纵特定神经元类型的工具通常成本高昂且耗时。该应用程序的目的是开发并向科学界发布一个广泛且多功能的工具包，用于操纵果蝇的神经系统，这是一个强大的遗传模型，已经产生了许多关于神经系统功能和发育的基本见解。该应用程序具有三个中心目标。首先，我们建议基于最近开发的 InSITE 系统生成 4,000 个新的转基因品系。这些菌株将允许对果蝇绝大多数神经元的基因表达进行细胞特异性操作。这些插入位点中的每一个都将被分子作图，并且每条线捕获的表达模式将在幼虫和成蝇大脑中被描述。其次，利用这个集合，我们将获得细胞类型特异性的交叉工具，以及独立的转录调控系统，从而允许在多种单独的细胞类型中独立地操纵基因表达。第三，我们将创建一个描述这些数据的数据库，使社区能够充分利用这一资源来解决广泛的科学问题。该集合将提供一个平台，用于将基因表达的多功能标记和驱动程序引入幼虫和成体神经系统中存在的大量神经元类型中，以便释放到果蝇群落中。一旦建立了该资源，使用和扩展收集的方法仅涉及可在任何实验室中进行调整的基本遗传杂交。我们期望这个集合将成为一个不断扩展的、高度通用且具有成本效益的工具集合，用于操纵神经系统和基因发现。