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: 9213724
• 负责人: IAN R WICKERSHAM
• 金额: $ 99.4万
• 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/9213724
• 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; Genome; Genomics; Human; Hypothalamic structure; Injection of therapeutic agent; Interneurons; Knock-out; Life; 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; Records Controls; 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; fly; in vivo; inhibitory neuron; insight; nervous system disorder; neural circuit; neuronal circuitry; nonhuman primate; novel therapeutics; optogenetics; receptor; research study; 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.

项目摘要 我们将使用高吞吐量技术来产生一组病毒载体，这些病毒向量将允许在大脑中特定神经元中的转基因选择性表达。与许多其他应用一起，这将允许对靶向神经元种群进行光遗传控制，记录和基因组修饰，而无需生产转基因或敲除线。这将为神经科学提供多功能且强大的工具集，这些工具将使一系列新的实验设计可能会产生对神经元电路组织以及正常认知和行为的生物学基础的重大见解，以及神经和精神疾病的功能障碍。此外，由于新工具还旨在在人类中起作用，因此它们可能会导致精神和神经系统疾病的重要新疗法。