G-protein coupled receptors for bioagent detection

用于生物制剂检测的 G 蛋白偶联受体

• 批准号: 6911649
• 负责人: Ethan A Lerner
• 金额: $ 45.41万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6911649
• 关键词: binding sites; bioengineering /biomedical engineering; biohazard detection; biosensor device; biotechnology; bioterrorism /chemical warfare; cell surface receptors; chemical models; chemicals; chemoreceptors; computer program /software; directed evolution; high throughput technology; microorganism antigen; microorganism toxin; polymerase chain reaction; rapid diagnosis; receptor binding; site directed mutagenesis

DESCRIPTION (provided by applicant): The nose is the most sophisticated chemical sensor ever devised. In less than a second a nose can detect and distinguish between vast numbers of chemicals. Olfaction works via odorants being detected by G-protein coupled receptors (GPCRs). The goal of this application is to develop a sensor for bioagents that mirrors the sensitivity, specificity and speed of the olfactory system. In addition to odorants, GPCRs are used by the body to detect photons, ions, sugars, biogenic amines, lipids, peptides and proteins. This apparent unrestricted nature of ligands to GPCRs suggests that they can be used to detect a broad range of chemicals including bioagents. The approach to developing a GPCR-based sensor is to subject a defined set of GPCRs to directed evolution in vitro via massive mutagenesis and subsequent screening for receptors with the appropriate specificities. The screening process uses a melanophore-based system for high-throughput identification of relevant receptors. In the future, optimized receptors will be arrayed and utilized in a device to which samples are introduced and results displayed via changes in spectrophotometric or fluorescent signals.

描述（由申请人提供）： 鼻子是有史以来最复杂的化学传感器。在不到一秒钟的时间里，鼻子可以检测和区分大量的化学物质。嗅觉通过G蛋白偶联受体（GPCR）检测气味剂来工作。该应用的目标是开发一种生物制剂传感器，反映嗅觉系统的灵敏度，特异性和速度。除了气味，GPCR还被身体用来检测光子、离子、糖、生物胺、脂质、肽和蛋白质。GPCR配体的这种明显的不受限制的性质表明它们可用于检测包括生物制剂在内的广泛的化学品。开发基于GPCR的传感器的方法是通过大规模诱变和随后筛选具有适当特异性的受体，使一组定义的GPCR在体外进行定向进化。筛选过程使用基于黑色素细胞的系统来高通量鉴定相关受体。在未来，优化的受体将被排列和利用在一个设备中，样品被引入和结果显示通过分光光度或荧光信号的变化。