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：
8068663
负责人：
Yi Wu
金额：
$ 18.87万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
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 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8068663
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 Fluorescence Resonance Energy Transfer 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 research study rho spatiotemporal src-Family Kinases submicron 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.

描述（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。这些网络必须在开发过程中正确形成，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中的一个或一组信号蛋白无法执行的方式。要了解这些蛋白质应该如何起作用，如果仅限于使用传统的生化和遗传方法，那么这并不是一件容易的事，因为蛋白质通常在细胞内的不同时间和位置扮演不同的角色。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强大方法是使研究人员能够在完整的神经回路细胞内的精确时间或位置打开或关闭它们。当前的提案旨在生成一组工具，这些工具可以在具有光脉冲的生活系统中打开或关闭蛋白质。通过这些工具获得的知识可以使我们更接近治疗许多神经系统疾病。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Labelling and optical erasure of synaptic memory traces in the motor cortex.

DOI：
10.1038/nature15257
发表时间：
2015-09-17
期刊：
Nature
影响因子：
64.8
作者：
Hayashi-Takagi A;Yagishita S;Nakamura M;Shirai F;Wu YI;Loshbaugh AL;Kuhlman B;Hahn KM;Kasai H
通讯作者：
Kasai H

F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling.

DOI：
10.1038/ncomms10493
发表时间：
2016-01-27
期刊：
Nature communications
影响因子：
16.6
作者：
Heemskerk N;Schimmel L;Oort C;van Rijssel J;Yin T;Ma B;van Unen J;Pitter B;Huveneers S;Goedhart J;Wu Y;Montanez E;Woodfin A;van Buul JD
通讯作者：
van Buul JD

Optogenetics: optical control of a photoactivatable Rac in living cells.