TRANSMISSION ELECTRON MICROSCOPE

描述(由申请人提供)：申请购买新的透射式电子显微镜(TEM)的资金，以支持华盛顿大学医学院(WUMS)由NIH资助的研究。这项提议将支持40多个NIH赠款项目，包括6个主要用户和12个次要用户，所有这些项目都具有丰富的、以前公布的EM经验，以及对电子显微镜的持续需求。计划中的EM应用包括涉及多器官系统和疾病模型的亚细胞病理的超微结构成像。此次收购将有助于EM设施进行日常研究，提高我们越来越多的研究人员的研究能力，无疑还将满足显微镜使用期间招聘的新研究人员的需求。具体地说，我们打算用新一代120千伏瞬变电磁JEOL 1400取代我们已有20多年历史的JEOL 1200瞬变电磁，它正在迅速老化并达到其可靠使用寿命的尽头。这款显微镜不仅将更高效、更可靠地完成我们目前的显微镜处理的所有任务，而且其改进的能力将以前所未有的方式扩展我们的研究。在过去的几年里，WUMS的研究人员发现我们的研究电子显微镜设备(由施密特博士指导，这项共享仪器拨款的PI)是推进各种生物问题的重要工具。到目前为止，我们最实质性和持续的使用涉及6个主要用户群体，他们在他们的研究计划中将TEM作为一个基本工具，以及12个次要用户，他们的使用更偶尔，但对解决个别实验问题同样重要。我们的显微镜已经向WUMS的研究人员提供，不分部门，按服务收费，并以补贴的费率提供给我们的糖尿病研究培训中心的成员，这有助于其维护。在这个已建立的EM设施内安装所要求的显微镜将在经验丰富的技术人员和主任的监督下协助用户培训、方案制定、日程安排和记账，他们将共同培训和协助用户。我们看到，研究生和博士后研究员(见表C3)对EM的使用兴趣日益浓厚，他们已经认识到超微结构为他们的研究增加了洞察力。一种新的显微镜将能够分析线粒体、轴突和神经末梢、髓鞘结构，并将有助于检查胰腺树突状细胞和破骨细胞的功能。华盛顿大学没有其他电子显微镜能够取代我们所要求的显微镜，要么是因为它太老了，要么是因为订阅量过大，限制了我们进行世界级研究的能力。 与公共卫生相关：我们的JEOL 1200透射式电子显微镜迅速接近过时，导致向我们庞大的用户群体提供超微结构分析的延迟，干扰了华盛顿大学医学院研究人员进行世界级科学研究的能力，并减缓了对神经退行性疾病、心脏疾病、胃肠道疾病、代谢疾病和骨骼疾病的分析。毫无疑问，在能力和可靠性增强的新一代电子显微镜的支持下，基础科学发现将有助于了解一些最普遍的人类健康祸害，并加快新疗法的开发和应用。

DESCRIPTION (provided by applicant): Funds are requested for the purchase of a new transmission electron microscope (TEM) to support NIH- funded research at Washington University Medical School (WUMS). This proposal will support 40+ NIH grant projects of 6 Major Users and 12 Minor Users, all with substantial, previously published EM experience and demonstrable ongoing need for electron microscopy. Planned EM applications include ultrastructural imaging of subcellular pathology involving multiple organ systems and disease models. This acquisition will contribute to the capability of the EM facility for day to day research TEM and to advance the research capability of a growing group of our investigators and will undoubtedly also serve the needs of new investigators recruited during the microscope's lifetime. Specifically, we intend to replace our 20+ year old JEOL 1200 TEM which is rapidly aging and reaching the end of its dependable lifespan with a new generation 120 kV TEM, the JEOL 1400. Not only will this microscope perform all of the tasks our current microscope handles more efficiently and dependably, but its improved capabilities will extend our research in ways not previously possible. Over the last few years investigators at WUMS have sought out our Research Electron Microscopy Facility (directed by Dr. Schmidt, the PI of this shared instrumentation grant) as an important tool in the advance of a variety of biologic problems. By far our most substantial and continuing use has involved 6 major user groups who have used TEM as an essential tool in their research programs and 12 minor users whose use has been more occasional but no less critical to resolving individual experimental issues. Our microscope has been available to WUMS investigators irrespective of department affiliation on a fee-for-service basis and at a subsidized rate to members of our Diabetes Research Training Center which contributes to its upkeep. Installation of the requested microscope within this established EM Facility will assist in user training, protocol development, scheduling and billing under the supervision of a highly experienced technical staff and Director who together will train and assist users. We have seen a burgeoning interest in the use of EM by graduate students and postdoctoral fellows (see Table C3) who have recognized the insight ultrastructure adds to their research. A new microscope will permit the analysis of mitochondria, axons and nerve terminals, myelin structure, and will contribute to the examination of pancreatic dendritic cell and osteoclast function. No other electron microscope at Washington University has the capability to substitute for the microscope we request, either because of its age or oversubscription which limits our ability to perform world-class research. PUBLIC HEALTH RELEVANCE: The rapidly approaching obsolescence of our JEOL 1200 transmission electron microscope resulting in delays in providing ultrastructural analysis to our large user group has interfered with the ability of investigators at Washington University School of Medicine to perform world-class science and slows the analysis of neurodegenerative, cardiac, gastrointestinal, metabolic and bone diseases. There is no doubt that basic scientific discoveries supported by a new generation electron microscope with enhanced capability and dependability will contribute to the understanding of some of the most prevalent scourges of human health and expedite the development and application of novel therapies.