A platform for high-throughput production of targeting systems for cell-type-specific transgene expression in wild-type animals

用于高通量生产野生型动物细胞类型特异性转基因表达的靶向系统的平台

• 批准号: 9349588
• 负责人: IAN R WICKERSHAM
• 金额: $ 98.46万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-09 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9349588
• 关键词: Achievement; Animals; Behavior; Binding; Binding Proteins; Biological; Brain; Brain region; Cells; Cerebral cortex; Characteristics; Choline O-Acetyltransferase; Clinical; Cognition; Deep Brain Stimulation; Directed Molecular Evolution; Engineering; Environment; Evolution; Experimental Designs; Functional disorder; Gene Expression; Genetic Transcription; Genome; Genomics; Human; Hypothalamic structure; Injection of therapeutic agent; Interneurons; Knock-out; Membrane; Membrane Proteins; Mental disorders; Modeling; Monitor; Mus; Neurology; Neuromodulator; Neurons; Neurosciences; Neurotransmitters; Parvalbumins; Patients; Perception; Pilot Projects; Play; Population; Pro-Opiomelanocortin; Production; Proteins; Psyche structure; Reagent; Role; Site-Directed Mutagenesis; Subgroup; Surface; System; Techniques; Technology; Time; Transgenes; Transgenic Animals; Transgenic Organisms; Viral Vector; Work; Yeasts; basal forebrain; base; calbindin; calcium indicator; calretinin; cell type; cognitive process; design; experimental study; fly; in vivo; inhibitory neuron; insight; nervous system disorder; neural circuit; neuronal circuitry; nonhuman primate; novel therapeutics; optogenetics; receptor; scaffold; selective expression; success; tool; transcription factor; transgene expression; yeast two hybrid system

PROJECT SUMMARY We will use high throughput techniques to produce a set of viral vectors that will allow selective expression of transgenes in specific populations of neurons in the brain. Along with many other applications, this will allow optogenetic control, recording, and genomic modification of targeted neuronal populations without the need for production of transgenic or knock-out lines. This will provide neuroscience with a versatile and powerful set of tools that will make possible a broad set of new experimental designs that are likely to yield major insights into the organization of neuronal circuits and the biological bases of normal cognition and behavior and the dysfunctions underlying neurological and mental disorders. Additionally, because the new tools are also designed to work in humans, they are likely to result in important new therapies for mental and neurological diseases.

项目总结 我们将使用高通量技术来生产一套病毒载体，使转基因能够在大脑中特定的神经元群体中选择性表达。与许多其他应用一起，这将允许对目标神经元群体进行光遗传控制、记录和基因组修改，而不需要生产转基因或敲除品系。这将为神经科学提供一套通用而强大的工具，使一系列新的实验设计成为可能，这些设计可能会对神经元电路的组织、正常认知和行为的生物学基础以及神经和精神障碍的潜在功能障碍产生重大见解。此外，由于这些新工具也是为人类设计的，它们可能会为精神和神经疾病带来重要的新疗法。