CAGED PROBES FOR CELLULAR PHYSIOLOGY

用于细胞生理学的笼式探针

• 批准号: 7365165
• 负责人: Joseph Pao Yung Kao
• 金额: $ 34.98万
• 依托单位: UNIVERSITY OF MD BIOTECHNOLOGY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7365165
• 关键词: Area; Biological; Biology; Calcium; Calcium Signaling; Cell physiology; Cells; Dendrites; Ion Channel; Kinetics; Knock-out; Life; Light; Lipids; Nerve; Neurotransmitter Receptor; Neurotransmitters; Reaction; Regulation; Research; Resolution; Signal Transduction; Synaptic plasticity; Tissues; absorption; caged molecule; chemical kinetics; computerized data processing; novel; photolysis; tool

DESCRIPTION (provided by applicant): A "caged" molecule is a photosensitive, but temporarily inert, precursor of a biologically active molecule. Light absorption transforms the precursor into a molecule with full bioactivity. Because a light beam can be easily focused and steered, and photochemical reactions are extremely fast, caged molecules are versatile tools for using light to manipulate biology with exceptionally high spatial and temporal resolution. The long-term objective is to develop a broad spectrum of novel photochemical tools that will enable cellular physiologists to use light to probe and control dynamic signaling processes in living cells and tissues. The proposed research has four foci: 1) Develop new "cages" that a) are strongly activated by light, b) show fast kinetics of product release on photolysis, c) give high yield of product when photolyzed, and d) are chemically and metabolically stable in the absence of light. 2) Develop new probes for cellular signaling, specifically cage neurotransmitters, lipid messengers, as well as probes that permit "photochemical knock-out" of neurotransmitter receptors and transporters, and ion channels. 3) Develop and optimize two probes of intracellular calcium signaling: a caged calcium and a caged "anti- calcium" for using light to rapidly generate and ablate intracellular calcium signals, respectively. 4) Apply the developed probes to cellular physiology research in the areas of signal processing by nerve terminals and dendrites, synaptic plasticity, and calcium regulation of cell excitability.

描述（由申请人提供）：“笼中”分子是生物活性分子的光敏但暂时惰性的前体。光吸收将前体转化为具有完全生物活性的分子。由于光束可以轻松聚焦和操纵，并且光化学反应极快，因此笼状分子是利用光以极高的空间和时间分辨率操纵生物的多功能工具。长期目标是开发一系列新型光化学工具，使细胞生理学家能够利用光来探测和控制活细胞和组织中的动态信号传导过程。拟议的研究有四个重点：1）开发新的“笼子”，a）被光强烈激活，b）显示光解产物释放的快速动力学，c）光解时产生高产量的产物，d）通过化学方法和在没有光的情况下代谢稳定。 2）开发用于细胞信号传导的新探针，特别是笼状神经递质、脂质信使，以及允许“光化学敲除”神经递质受体和转运蛋白以及离子通道的探针。 3) 开发和优化细胞内钙信号传导的两种探针：笼状钙和笼状“抗钙”，分别用于利用光快速产生和消除细胞内钙信号。 4）将开发的探针应用于神经末梢和树突信号处理、突触可塑性和细胞兴奋性钙调节等领域的细胞生理学研究。