Engineering a new class of optogenetic tools targeting small GTPases and kinases

设计针对小 GTP 酶和激酶的新型光遗传学工具

基本信息

批准号：
7978445
负责人：
Yi Wu
金额：
$ 1.78万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-15 至 2010-07-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7978445
关键词：
Address Affinity Animals Area Back Binding Biochemical Genetics Biosensor Brain C-terminal Catalytic Domain Cells Chimera organism Development Dissociation Distant Docking Engineering Family Flavins Fluorescence Genetic Homologous Gene Imaging Device Integral Membrane Protein Intelligence Intracellular Signaling Proteins Ion Channel Knowledge Lead Learning Life Light Lighting Location Mechanics Mediating Memory Microscopy Modeling Molecular Monomeric GTP-Binding Proteins Mutation N-terminal Nature Neurons One-Step dentin bonding system Organism Outcome Oxygen Pathology Peptides Phosphotransferases Photoreceptors Physiologic pulse Plant Photoreceptors Process Protein Kinase Protein Kinase Inhibitors Proteins Reagent Regulation Reliance Research Research Personnel Role Signal Transduction Signaling Protein Therapeutic Time Tissues Work analog base cellular imaging cofactor empowered in vivo inhibitor/antagonist insight irradiation kinase inhibitor member mutant nervous system disorder neural circuit neuron development novel phototropin prevent protein function protein kinase A kinase protein kinase inhibitor public health relevance research study rho spatiotemporal src-Family Kinases tool tool development voltage

项目摘要

DESCRIPTION (provided by applicant): Our thought processes rely on networks of nerve cells called neurons. These networks must be properly formed during development and the neurons must be able to communicate correctly with each other for our brains to function normally. When neurological disorders occur, they can often be traced back to how one or a group of signaling proteins within neurons failed to perform. To understand how these proteins should have worked is not an easy task if one is limited to using traditional biochemical and genetic approaches, because the proteins often carry out different roles at different times and locations inside the cells. One powerful way to identify how the functions of these proteins depends on the location and timing of their activity would be to enable investigators to switch them on or off at precise times or locations inside the cells of intact neural circuits. The current proposal aims to generate a set of tools that can switch proteins on or off in living systems with a pulse of light. Knowledge gained with these tools can lead us one step closer to curing many neurological disorders. PUBLIC HEALTH RELEVANCE: The proposed studies will provide novel imaging tools that empower investigators to directly interrogate and understand the activities of specific signaling proteins at precise times and locations within specific types of neurons in vivo, the outcomes of which can provide mechanistic insights into the pathology and therapeutics of many neurological disorders, and may eventually unravel the molecular basis of intelligence, memory and learning.

描述（由申请人提供）：我们的思维过程依赖于称为神经元的神经细胞网络。这些网络必须在发育过程中正确形成，并且神经元必须能够彼此正确通信，以使我们的大脑正常运作。当神经系统疾病发生时，通常可以追溯到神经元内的一个或一组信号蛋白如何无法发挥作用。如果仅限于使用传统的生化和遗传学方法，了解这些蛋白质如何发挥作用并不是一件容易的事，因为这些蛋白质通常在细胞内的不同时间和位置发挥不同的作用。确定这些蛋白质的功能如何取决于其活动的位置和时间的一种有效方法是使研究人员能够在完整神经回路细胞内的精确时间或位置打开或关闭它们。目前的提案旨在生成一套工具，可以用光脉冲打开或关闭生命系统中的蛋白质。通过这些工具获得的知识可以使我们更接近治愈许多神经系统疾病。公共健康相关性：拟议的研究将提供新颖的成像工具，使研究人员能够直接询问和了解体内特定类型神经元内特定信号蛋白在精确时间和位置的活动，其结果可以提供对病理学的机制见解以及许多神经系统疾病的治疗方法，并可能最终揭示智力、记忆和学习的分子基础。