Zinc Fluorescence Biosensing and Imaging Technology

锌荧光生物传感与成像技术

• 批准号: 6812778
• 负责人: RICHARD Blair THOMPSON
• 金额: $ 42.21万
• 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/6812778
• 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）：拟议工作的主要目的是开发大脑中游离锌的荧光指示系统，具有提高的选择性，灵敏度和可校准的响应，并在细胞内进行校准。当前的小分子指标不足以敏感，选择性或两者兼而有之，并且许多指标无法以时尚的比率，各向异性或寿命）进行响应，可以准确地原位校准。我们的努力已经取得了一些成功，我们预计它们将在理解体内锌在大脑中的生理作用以及其在缺血性中风，癫痫，阿尔茨海默氏病和钝性创伤中的病理作用。我们的具体目的专注于开发新方法，并利用它们来回答锌神经生物学中重要性的问题。它们包括使用激发率方法在细胞核中定量成像的无锌水平；使用新型的纤维光学传感器测量狗缺血模型中的锌释放；并在线粒体中定量成像锌水平。如果成功，我们预计我们的技术将用于理解和开发上述条件的治疗方法。