300 keV Liquid Helium Robotic Microscope

描述（由申请人提供）：申请资金购买最先进的300 keV液氦透射电子冷冻显微镜和场发射枪。为了充分利用NIH项目提供的资金，该显微镜大约40%的资金将来自弗吉尼亚大学的机构资源。其中两个pi使用电子冷冻显微镜（cryo-EM）作为他们的主要工具，并将是该显微镜的主要用户。此外，这台仪器的获得对于为弗吉尼亚大学招募第三名电子显微镜专家至关重要。目前在弗吉尼亚大学有一大批由美国国立卫生研究院资助的研究人员，他们将从这台显微镜的出现中受益匪浅。对这台仪器的需求源于最近一些项目的进展，这些项目表明弗吉尼亚大学现有的显微镜限制了继续的进展。这些项目包括螺旋细丝、二十面体病毒和二维晶体。最近在几个领域取得了突破，比如细菌菌毛丝状噬菌体和HIV-1衣壳的重建，一些迹象表明，使用最先进的显微镜可能会取得更大的进展。所提出的显微镜具有包络功能，其衰减速度比目前可用的显微镜慢得多，这将使我们能够获得更高分辨率的结构。公共卫生相关性：我们将使用更高分辨率的电子显微镜来推进目前由NIH资助的项目。我们将从这台显微镜获得更高分辨率的结构，它将对从细菌致病机制到心脏病、癌症到艾滋病等公共卫生问题产生影响。

DESCRIPTION (provided by applicant): Funds are requested for purchase of a state-of-the-art 300 keV liquid helium Transmission Electron Cryo-Microscope with a Field Emission Gun. To leverage the funds provided by this NIH program, approximately 40% of the funds for this microscope will be derived from institutional sources at the University of Virginia. Two of the PIs use electron cryo-microscopy (cryo-EM) as their primary tool and will be the main users of this microscope. In addition, the acquisition of this instrument will be crucial for recruiting a third electron microscopist to the University of Virginia. There exists a significant community of NIH-funded investigators currently at the University of Virginia who will benefit greatly from the presence of this microscope. The need for this instrument arises from recent progress on a number of projects which show that existing microscopes at the University of Virginia limit continued progress. These projects include helical filaments, icosahedral viruses and two-dimensional crystals. Recent breakthroughs have been made in several areas, such as reconstructions of bacterial pili filamentous phage and HIV-1 capsids, and several indications suggest that much greater progress may be possible with a state-of-the-art microscope. The proposed microscope has an envelope function that decays much more slowly than the microscopes currently available, and this will allow us to obtain higher resolution structures. PUBLIC HEALTH RELEVANCE: We will use a higher resolution electron microscope to advance projects currently funded by the NIH. The higher resolution structures that we will obtain from this microscope will have an impact on matters of public health ranging from bacterial pathogenesis to heart disease to cancer to AIDS.