Confocal Microscope Core for Translational Research

描述（由申请人提供）：本提案要求国家研究资源中心提供资金，用于购买一台用于固定细胞和活细胞成像的徕卡TCS SP5光谱共聚焦显微镜，以提高宾夕法尼亚大学科学研究的质量和便宜性。SP5共聚焦仪器的核心设备将由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传递以及对细胞结构和生理反应的影响，(2)阻塞性睡眠呼吸暂停中更精确的缺氧、氧化损伤和内质网损伤指标，(3)线虫体内神经元活动，以确定睡眠机制，(4)在精神分裂症模型的研究中，通过z堆栈在无扭曲的3D图像中牢固地建立细胞内定位；(5)阐明睡眠/觉醒回路老化过程中细胞骨架和神经元突触的变化。这台机器也将提供给宾夕法尼亚大学（University of Pennsylvania）所有由NIH资助的首席研究人员，他们中的许多人由于等待共焦病毒的时间而经历了NIH项目的延误。我们已经制定了一个共享的仪器操作系统，将由宾夕法尼亚大学战略核心设施咨询委员会监督，以确保主要用户研究人员和校园内其他人的合理使用时间。我们设想通过这种共享的工具使用来发展许多富有成效的合作。有强有力的机构承诺延长维护这些设备的时间。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，然后开发针对多种疾病的新疗法，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：

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.