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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(申请人提供)：我们的思维过程依赖于被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，神经元必须能够正确地相互通信，我们的大脑才能正常运作。当神经性疾病发生时，它们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。如果局限于使用传统的生化和遗传方法，要了解这些蛋白质应该如何发挥作用并不是一件容易的任务，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。要确定这些蛋白质的功能如何依赖于它们活动的位置和时间，一个有效的方法是让研究人员能够在完整的神经回路细胞内的准确时间或位置打开或关闭它们。目前的提议旨在产生一套工具，可以通过光脉冲来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带领我们离治愈许多神经疾病更近一步。与公共健康相关：拟议的研究将提供新的成像工具，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准确时间和位置的活动，其结果可以为许多神经疾病的病理和治疗提供机械性见解，并最终可能揭开智力、记忆和学习的分子基础。