TRANSMISSION ELECTRON MICROSCOPE

描述（由申请人提供）：申请资金用于购买一台新的透射电子显微镜（TEM），以支持华盛顿大学医学院（WUMS）的NIH资助的研究。该提案将支持40多个NIH资助项目，其中包括6个主要用户和12个次要用户，所有这些用户都具有大量先前发表的EM经验和对电子显微镜的持续需求。计划中的EM应用包括涉及多个器官系统和疾病模型的亚细胞病理学的超微结构成像。此次收购将有助于EM设施的日常研究TEM的能力，并提高我们越来越多的研究人员的研究能力，无疑也将满足在显微镜的生命周期内招募的新研究人员的需求。具体来说，我们打算用新一代120 kV TEM JEOL 1400替换已经使用了20多年的JEOL 1200 TEM，该TEM正在迅速老化，并达到其可靠寿命的终点。这台显微镜不仅能更有效、更可靠地完成我们现有显微镜所能处理的所有任务，而且其改进后的功能将以前所未有的方式扩展我们的研究。在过去的几年里，WUMS的研究人员已经找到了我们的研究电子显微镜设备（由施密特博士指导，该共享仪器赠款的PI）作为推进各种生物学问题的重要工具。到目前为止，我们最实质性的和持续的使用涉及6个主要的用户群体，他们在他们的研究计划中使用TEM作为一个必不可少的工具，12个小用户，他们的使用更偶然，但对解决个别实验问题同样重要。我们的显微镜已经提供给WUMS研究人员，无论部门隶属关系，以收费服务为基础，并以补贴的价格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。在该已建立的EM设施内安装所需显微镜将有助于在经验丰富的技术人员和主管的监督下进行用户培训、方案制定、调度和计费，他们将共同培训和协助用户。我们已经看到研究生和博士后研究员对EM的使用产生了浓厚的兴趣（见表C3），他们认识到超微结构的洞察力有助于他们的研究。一种新的显微镜将允许线粒体，轴突和神经末梢，髓鞘结构的分析，并将有助于胰腺树突状细胞和破骨细胞功能的检查。华盛顿大学没有其他电子显微镜有能力取代我们要求的显微镜，无论是因为它的年龄或超额认购，这限制了我们进行世界级研究的能力。 公共卫生相关性：我们的JEOL 1200透射电子显微镜的快速接近过时导致延迟提供超微结构分析给我们的大用户群，干扰了华盛顿大学医学院的研究人员进行世界一流科学的能力，减缓了神经退行性疾病，心脏病，胃肠道，代谢和骨骼疾病的分析。毫无疑问，由新一代电子显微镜支持的基础科学发现具有增强的能力和可靠性，将有助于理解人类健康的一些最普遍的疾病，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.