Zinc Fluorescence Biosensing and Imaging Technology

锌荧光生物传感与成像技术

• 批准号: 7112422
• 负责人: RICHARD Blair THOMPSON
• 金额: $ 37.83万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-15 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7112422
• 关键词: PC12 cells; bioimaging /biomedical imaging; biotechnology; brain imaging /visualization /scanning; carbonate dehydratase; cell nucleus; cerebrospinal fluid; chemical structure function; clinical research; disease /disorder model; dogs; epilepsy; fiber optics; flow cytometry; fluorescent dye /probe; human tissue; ischemia; laboratory rat; metalloproteins; mitochondria; neural transmission; neurobiology; protein binding; technology /technique development; zinc

DESCRIPTION (provided by applicant): The major thrust of the proposed work is to develop fluorescent indicator systems for free zinc in the brain, with improved selectivity, sensitivity, and calibratable response both intracellulady and extracellularly. Current small molecule indicators are insufficiently sensitive, selective, or both, and many do not respond in a fashion (intensity ratio, anisotropy, or lifetime) that can be accurately calibrated in situ. Our efforts have already met some success, and we anticipate that they will be valuable in understanding the physiological roles of zinc in the brain in vivo, as well as its pathological roles in ischemic stroke, epilepsy, Alzheimer's disease, and blunt trauma. Our specific aims are focused on developing new methods and using them to answer questions of importance in zinc neurobiology. They include quantitatively imaging free zinc levels in the cell nucleus, using an excitation ratiometric approach; measuring zinc release in a dog ischemia model using a novel fiber optic sensor;, measuring zinc levels during seizures in a rat epilepsy model; and quantitatively imaging zinc levels in mitochondria. If successful, we anticipate that our technology will be of use in understanding and developing treatments for the conditions listed above.

描述（由申请人提供）：所提议工作的主要目的是开发大脑中游离锌的荧光指示剂系统，该系统具有改进的选择性、灵敏度和细胞内和细胞外的可校准响应。目前的小分子指示剂灵敏度和选择性不够，或者两者兼而有之，而且许多指示剂不能以可在原位精确校准的方式（强度比、各向异性或寿命）做出响应。我们的努力已经取得了一些成功，我们预计它们对于理解锌在体内大脑中的生理作用，以及它在缺血性中风、癫痫、阿尔茨海默氏病和钝性创伤中的病理作用将是有价值的。我们的具体目标是开发新方法并利用它们来回答锌神经生物学中的重要问题。它们包括使用激发比率方法对细胞核中的游离锌水平进行定量成像；使用新型光纤传感器测量狗缺血模型中的锌释放；测量大鼠癫痫模型癫痫发作期间的锌水平；并对线粒体中的锌水平进行定量成像。如果成功，我们预计我们的技术将有助于理解和开发针对上述情况的治疗方法。