A universal photoswitch system for optical control of neuronal receptors
用于神经元受体光学控制的通用光电开关系统
基本信息
- 批准号:8255457
- 负责人:
- 金额:$ 30.39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-07-22 至 2013-04-30
- 项目状态:已结题
- 来源:
- 关键词:AntibodiesBiochemicalBiologyBrain-Derived Neurotrophic FactorCell Surface ProteinsCell Surface ReceptorsCell physiologyDevelopmentEffectivenessFamilyG Protein-Coupled Receptor GenesG-Protein-Coupled ReceptorsGoalsGrowth Factor ReceptorsHealthIon ChannelLigandsLightMethodsNatureNeuronsNeurophysiology - biologic functionNeurotrophic Tyrosine Kinase Receptor Type 2OpticsPeptidesPhotophobiaReceptor ActivationReceptor InhibitionReceptor Protein-Tyrosine KinasesRegulationRoleSystemTechniquesTestingTissuesTranslatingazobenzenebrain-derived growth factorcombinatorialinhibitor/antagonistmeetingsmemberneuropeptide Yneurotrophic factorreceptorresponsetool
项目摘要
DESCRIPTION (provided by applicant):
One of the most exciting technical developments in biology in recent years is the emergence of photochemical methods for controlling electrical activity with light. Our goal in this project is to develop a broadly applicable method for controlling other aspects of cellular function by generating tools for conferring light sensitivity on a broad range of cell surface receptors and ion channels. To meet this challenge we will use a modular approach, utilizing a single "Universal Photoswitch" as the key light-sensing component. The photoswitch contains at its core the small isomerizable azobenzene moiety, which shortens and lengthens in response to 380 and 500 nm light, respectively. We will use this photoswitch to indirectly regulate receptor and channel activity, through an "adapter peptide", which contains a "capture domain", which recognizes the short, but not the long configuration of the photoswitch, and a ligand domain, which contains a peptide activator or inhibitor of the targeted cell surface receptor or ion channel. The capture domain is kept constant among all adapter peptides, allowing control by a single Universal Photoswitch, but the nature of ligand domain is tailored to regulate a specific receptor. Several strategies will be used to translate light-dependent capture of the adapter peptide into receptor activation or inhibition. These include dimerizing the adapter peptide with a dimeric photoswitch to activate growth factor receptors, and delivering the adapter peptide, including the ligand, to a G-protein coupled receptor via an antibody-tethered photoswitch. Other strategies may be developed to activate different types of receptors and ion channels. We will test the effectiveness of the Universal Photoswitch approach on two example receptors: the TrkB receptor for brain-derived growth factor (BDNF), a member of the neurotrophin family of receptor tyrosine kinases, and the receptor for neuropeptide Y, which is a GPCR-type receptor. Generating a method for light-sensitive regulation of these receptors will allow examination of their roles in development and neural function in intact tissue with unprecedented precision, but more importantly, it will demonstrate the emergence of a powerful new technique for receptor regulation that can be applied to any cell surface protein for which a known peptide ligand exists.
描述(由申请人提供):
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(0)
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RICHARD H KRAMER其他文献
RICHARD H KRAMER的其他文献
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{{ truncateString('RICHARD H KRAMER', 18)}}的其他基金
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Targeting the retinoic acid signaling pathway for mitigating visual impairmen in retinal degenerative disorders
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Targeting the retinoic acid signaling pathway for mitigating visual impairmen in retinal degenerative disorders
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10844853 - 财政年份:2015
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Understanding How Photoswitches Restore Visual Function in Blind Mice
了解光电开关如何恢复失明小鼠的视觉功能
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$ 30.39万 - 项目类别:
Understanding how photoswitches restore visual function in blindness
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- 批准号:
10212754 - 财政年份:2015
- 资助金额:
$ 30.39万 - 项目类别:
Targeting the retinoic acid signaling pathway for mitigating visual impairmen in retinal degenerative disorders
靶向视黄酸信号通路以减轻视网膜退行性疾病中的视力障碍
- 批准号:
10684166 - 财政年份:2015
- 资助金额:
$ 30.39万 - 项目类别:
A universal photoswitch system for optical control of neuronal receptors
用于神经元受体光学控制的通用光电开关系统
- 批准号:
7726422 - 财政年份:2009
- 资助金额:
$ 30.39万 - 项目类别:
A universal photoswitch system for optical control of neuronal receptors
用于神经元受体光学控制的通用光电开关系统
- 批准号:
7898562 - 财政年份:2009
- 资助金额:
$ 30.39万 - 项目类别:
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