Optogenetics for all: A general method for optical control of protein activity

所有人的光遗传学:蛋白质活性光学控制的通用方法

基本信息

  • 批准号:
    8564060
  • 负责人:
  • 金额:
    $ 80.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-09-30 至 2018-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Optical control of genetically defined protein activities, i.e. optogenetic regulation of proteins, has long been a dream in biology. If we could develop a generalizable method to optically control activities of proteins of interest, it could profoundly transform biological experimentation and impart new capabilities to gene- and cell-based therapies. For instance, the cellular functions that proteins coordinate, such as survival, apoptosis, differentiation, migration or connectivity (in the nervous system) could be controlled in vivo to study organismal physiology with micron-level resolution. Therapeutically implanted cells could be similarly controlled by light to precisely focus treatment at desired anatomical locations. There are countless other possible applications. Given these advantages of optical protein regulation, considerable efforts have been expended to adapt known light-responsive signaling domains to regulate mammalian proteins. However, existing strategies require extensive screening to create light-responsive proteins, or rely on protein relocalization to indirectly regulate activity. As a result, these methods have been used to control only a few proteins. Thus there exists a need for a method to create light-regulated proteins of interest that is generalizable. We have recently discovered a new class of light-mediated protein-protein interaction, and translated this discovery into a generalizable method for controlling protein activities with light. We hypothesized that fluorescent proteins (FPs) could undergo light-dependent conformational changes that drive changes in oligomerization state. Indeed, we found that tetrameric and dimeric variants of the reversibly photoswitching green FP Dronpa undergo dissociation as they are switched from bright to dark states by cyan light. We then discovered that fusing Dronpa domains at both ends of an enzymatic domain of interest cages it in the dark but allows uncaging upon illumina
描述(由申请人提供):光控制遗传定义的蛋白质活性,即光遗传调节蛋白质,一直是生物学的梦想。如果我们能够开发出一种可推广的方法来光学控制感兴趣的蛋白质的活性,它可能会深刻地改变生物实验,并赋予基于基因和细胞的治疗新的能力。例如,蛋白质协调的细胞功能,如生存、凋亡、分化、迁移或连接(在神经系统中),可以在体内控制,以微米级的分辨率研究生物体生理学。治疗性植入的细胞同样可以通过光来控制,以精确地将治疗集中在所需的解剖位置。还有无数其他可能的应用。鉴于光学蛋白调控的这些优势,人们已经花费了大量的努力来适应已知的光响应信号域来调节哺乳动物蛋白。然而,现有的策略需要广泛的筛选来产生光反应蛋白,或者依靠蛋白质的重新定位来间接调节活性。因此,这些方法仅用于控制少数蛋白质。因此,需要一种方法来制造感兴趣的光调节蛋白质

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(1)

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Michael Z. Lin其他文献

Synaptic basis of feature selectivity in hippocampal neurons
海马神经元特征选择性的突触基础
  • DOI:
    10.1038/s41586-024-08325-9
  • 发表时间:
    2024-12-18
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    Kevin C. Gonzalez;Adrian Negrean;Zhenrui Liao;Satoshi Terada;Guofeng Zhang;Sungmoo Lee;Katalin Ócsai;Balázs J. Rózsa;Michael Z. Lin;Franck Polleux;Attila Losonczy
  • 通讯作者:
    Attila Losonczy
An optimized luciferin formulation for NanoLuc-based in vivo bioluminescence imaging
用于基于 NanoLuc 的体内生物发光成像的优化荧光素制剂
  • DOI:
    10.1038/s41598-025-97366-9
  • 发表时间:
    2025-04-15
  • 期刊:
  • 影响因子:
    3.900
  • 作者:
    Chao Gao;Yan Wu;Connor Fitzgerald;Hui Wang;Tim Ugo;Tetsuo Uyeda;Wenhui Zhou;Yichi Su;Thomas A. Kirkland;Michael Z. Lin
  • 通讯作者:
    Michael Z. Lin
Functional and Structural Characterization of A New Monomeric Far-Red Fluorescent Protein
  • DOI:
    10.1016/j.bpj.2009.12.1158
  • 发表时间:
    2010-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Michael Z. Lin;Michael R. McKeown;Ho Leung Ng;Tom Alber;Roger Y. Tsien
  • 通讯作者:
    Roger Y. Tsien
On the cutting edge: protease-based methods for sensing and controlling cell biology
处于前沿:基于蛋白酶的细胞生物学传感与控制方法
  • DOI:
    10.1038/s41592-020-0891-z
  • 发表时间:
    2020-07-13
  • 期刊:
  • 影响因子:
    32.100
  • 作者:
    H. Kay Chung;Michael Z. Lin
  • 通讯作者:
    Michael Z. Lin
Pharmacodynamics of Akt drugs revealed by a kinase-modulated bioluminescent indicator
一种激酶调节的生物发光指示剂揭示的 Akt 药物的药效学
  • DOI:
    10.1038/s41589-025-01846-y
  • 发表时间:
    2025-02-11
  • 期刊:
  • 影响因子:
    13.700
  • 作者:
    Yan Wu;Chenzhou Hao;Chao Gao;Matt Hageman;Sungmoo Lee;Thomas A. Kirkland;Nathanael S. Gray;Yichi Su;Michael Z. Lin
  • 通讯作者:
    Michael Z. Lin

Michael Z. Lin的其他文献

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{{ truncateString('Michael Z. Lin', 18)}}的其他基金

Development of selective and potent protease inhibitors for corona and other pandemic viruses
开发针对冠状病毒和其他大流行病毒的选择性有效蛋白酶抑制剂
  • 批准号:
    10514273
  • 财政年份:
    2022
  • 资助金额:
    $ 80.25万
  • 项目类别:
The power of positivity: a novel class of voltage indicators for high-fidelity brain activity imaging
积极性的力量:用于高保真大脑活动成像的新型电压指示器
  • 批准号:
    10294164
  • 财政年份:
    2021
  • 资助金额:
    $ 80.25万
  • 项目类别:
Chemogenetic control of kinase and phosphatase activity by modulating autoinhibition
通过调节自抑制对激酶和磷酸酶活性进行化学遗传学控制
  • 批准号:
    10195182
  • 财政年份:
    2021
  • 资助金额:
    $ 80.25万
  • 项目类别:
Bioluminescent indicators for noninvasive imaging of acetylcholine release
用于乙酰胆碱释放无创成像的生物发光指示器
  • 批准号:
    10196839
  • 财政年份:
    2021
  • 资助金额:
    $ 80.25万
  • 项目类别:
Chemogenetic control of kinase and phosphatase activity by modulating autoinhibition
通过调节自抑制对激酶和磷酸酶活性进行化学遗传学控制
  • 批准号:
    10371123
  • 财政年份:
    2021
  • 资助金额:
    $ 80.25万
  • 项目类别:
Noninvasive bioluminescent imaging of neuronal activity in freely behaving animals
自由行为动物神经元活动的无创生物发光成像
  • 批准号:
    9906190
  • 财政年份:
    2019
  • 资助金额:
    $ 80.25万
  • 项目类别:
Protein voltage sensors: kilohertz imaging of neural dynamics in behaving animals
蛋白质电压传感器:行为动物神经动力学的千赫兹成像
  • 批准号:
    8827201
  • 财政年份:
    2014
  • 资助金额:
    $ 80.25万
  • 项目类别:
Optogenetics for all: A general method for optical control of protein activity
所有人的光遗传学:蛋白质活性光学控制的通用方法
  • 批准号:
    8896827
  • 财政年份:
    2013
  • 资助金额:
    $ 80.25万
  • 项目类别:
Optogenetics for all: A general method for optical control of protein activity
所有人的光遗传学:蛋白质活性光学控制的通用方法
  • 批准号:
    9132820
  • 财政年份:
    2013
  • 资助金额:
    $ 80.25万
  • 项目类别:
A Molecular Tag for Drug-Regulated Synthesis of Specific Proteins
用于药物调控合成特定蛋白质的分子标签
  • 批准号:
    8733708
  • 财政年份:
    2011
  • 资助金额:
    $ 80.25万
  • 项目类别:

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