Confocal Microscope Core for Translational Research

描述（由申请人提供）：在本提案中，国家研究资源中心要求提供资金，用于购买Leica TCS SP 5光谱共聚焦显微镜，用于固定和活细胞成像，以提高宾夕法尼亚大学进行的科学研究的质量和便利性。将为SP 5共聚焦仪器开发一个核心设施，供7名主要研究人员定期使用，用于（1）确认囊性纤维化和哮喘的基因递送及其对细胞结构和生理反应的影响，（2）阻塞性睡眠呼吸暂停中缺氧、氧化损伤和内质网损伤的更精确指标，（3）C. elegans来识别睡眠机制，（4）z-堆栈，以牢固地建立无畸变3D图像的细胞内定位，用于精神分裂症模型的研究，以及（5）阐明睡眠/觉醒回路老化中细胞骨架和神经元突触的改变。这台机器也将提供给宾夕法尼亚大学的所有NIH资助的主要研究人员，其中许多人在NIH项目中遇到了延误，因为等待共焦镜的时间。我们已经制定了一个共享的仪器操作系统，将由宾夕法尼亚战略核心设施咨询委员会监督，这将确保主要用户调查人员和校园内其他人的公平使用时间。我们设想通过这种共享工具的使用来开发许多富有成效的合作。有强有力的机构承诺长期维护这一设备。相关性：该仪器将使我们能够更精确地定义许多疾病过程中的分子相互作用，其首要目标是确定疾病的机制，然后为各种疾病开发新的治疗方法，包括睡眠呼吸暂停，哮喘，肺动脉高压，中风，囊性纤维化，动脉粥样硬化以及衰老的认知和睡眠障碍。公共卫生相关性： 共聚焦将用于增强转化科学，以更好地识别许多疾病过程的分子机制，包括囊性纤维化、肺动脉高压、哮喘、睡眠呼吸暂停、动脉粥样硬化、中风、精神分裂症和睡眠障碍。阐明这些疾病和病症的分子机制将直接用于开发针对这些重要医学病症和其他病症的更新更有效的疗法。

DESCRIPTION (provided by applicant): In this proposal, funds are requested from the National Center of Research Resources for purchase of a Leica TCS SP5 spectral confocal microscope equipped for fixed and live cell imaging to advance both the quality and expedience of scientific studies performed at the University of Pennsylvania. A core facility will be developed for the SP5 confocal instrument to be used regularly by seven primary investigators for (1) confirmation of gene delivery for cystic fibrosis and asthma in parallel with effects on cytoarchitecture and physiological responses, (2) more precise indices of hypoxia, oxidative damage and endoplasmic reticulum injury in obstructive sleep apnea, (3) in vivo neuronal activity in C. elegans to identify mechanisms of sleep, (4) z-stacks to firmly establish intracellular localization in distortion-free 3D images for studies in models of schizophrenia, and (5) elucidation of alterations in cytoskeleton and neuronal synapses in aging of sleep/wake circuits. The machine would also be made available to all NIH-funded principal investigators at the University of Pennsylvania, many of whom experience delays in NIH projects because of wait times for confocals. We have worked out a shared instrument operating system that will be overseen by the Penn Strategic Core Facility Advisory Committee that will ensure fair use times for both major user investigators and others on campus. We envision numerous productive collaborations to develop through this shared instrument usage. There is strong institutional commitment to maintain this equipment for extended time. Relevance: This instrument will enable us to more precisely define the molecular interactions in many disease processes with overriding goals to identify mechanisms of disease and then develop novel therapies for a diverse collection of diseases including sleep apnea, asthma, pulmonary hypertension, stroke, cystic fibrosis, atherosclerosis and cognitive and sleep disorders of aging. PUBLIC HEALTH RELEVANCE: The confocal would be used to enhance translational science to better identify molecular mechanisms underlying numerous disease processes including cystic fibrosis, pulmonary hypertension, asthma, sleep apnea, atherosclerosis, stroke, schizophrenia and sleep disorders. Elucidation of the molecular mechanisms of these diseases and conditions will be used directly to develop newer more effective therapies for these significant medical disorders, and others.