Acquisition of a Liquid Helium Cryo-Electron Microscope

说明(申请人提供)：本方案是为购买一台300kVFEC液氦冷冻电子显微镜用于单颗粒分析的资金。低温电子显微镜(CRYO-EM)是显示大分子组装结构的一种强有力的手段。两项技术进步，场发射枪(FEG)电子源和液氦冷却样品台，提供了原子或近原子分辨率的潜力。由美国国立卫生研究院资助的几个正在进行的生物医学研究项目将从获得液氦冷冻显微镜中受益匪浅。这些包括对腺病毒载体和腺病毒受体复合体的成像；DNA依赖蛋白激酶(DNA-PK)DNA双链断裂修复复合体；以及野生型和敲除小鼠穹顶和重组拱顶状颗粒。金库是一种普遍存在的高度保守的细胞成分，在癌细胞的多药耐药中发挥作用。新的显微镜最终将安置在加州大学洛杉矶分校的加州纳米系统研究所(CSNI)科学法院大楼内，该大楼正处于建筑规划阶段，计划于2004年完工。FEI公司已经在加州大学洛杉矶分校克拉普分子成像研究所确定并评估了所需显微镜的临时位置，毗邻加州大学洛杉矶分校目前的120KV液氮冷冻电子显微镜。CNSI寻求促进加州大学洛杉矶分校医学院、文学与科学学院、工程学院以及加州大学洛杉矶分校和加州大学圣巴巴拉分校的研究人员之间的跨学科互动。分子、细胞和机体水平的成像是CNSI的一个重要方面。CNSI是被选中获得加利福尼亚州1亿美元支持的三项研究努力之一。近30家企业合作伙伴已经承诺支持CNSI。如果液氦冷冻显微镜获得资金，CNSI将寻找一家企业合作伙伴，如一家制药公司，帮助为显微镜的长期运营成本提供资金。显微镜长期运营的财务计划包括加州大学洛杉矶分校为显微镜运营费用做出的重大额外承诺。

DESCRIPTION (provided by applicant): This proposal is for funds to purchase a 300kV FEC liquid helium cryo-electron microscope for single particle analysis. Cryo-electron microscopy (cryo-EM) has emerged as a powerful approach for visualizing the structures of macromolecular assemblies. Two technological advances, the field emission gun (FEG) electron source and a liquid helium-cooled specimen stage, provide the potential of atomic, or near atomic, resolution. Several ongoing NIH-funded biomedical research projects will benefit greatly from access to a liquid helium cryo-microscope. These include imaging of adenovirus vectors and adenovirus-receptor complexes; DNA-dependent protein kinase (DNA-PK) DNA double-strand break repair complexes; and wild-type and knock-out mouse vaults and recombinant vault-like particles. The vault is a ubiquitous and highly conserved cellular component that has a role in multidrug resistance in cancer cells. The new microscope will ultimately be housed in the California NanoSystems Institute (CSNI) Court of Sciences building at UCLA, which is in the architectural planning phase and is scheduled for completion in 2004. A temporary location for the requested microscope has been identified and evaluated by the FEI Company in the Crump Institute for Molecular Imaging at UCLA, adjacent to UCLA's current 120kV liquid nitrogen cryo-electron microscope. The CNSI seeks to foster interdisciplinary interactions between researchers in the UCLA School of Medicine, College of Letters and Science, School of Engineering, and between UCLA and UC Santa Barbara. Imaging at the molecular, cellular, and organismal levels is an important facet of the CNSI. The CNSI is one of three research efforts selected to receive $100 million in support from the state of California. Nearly 30 corporate partners have already pledged support for the CNSI. If the liquid helium cryo-microscope is funded, CNSI will seek a corporate partner, such as a pharmaceutical company, to help fund the long term operating costs of the microscope. The financial plan for the long term operation of the microscope includes a significant additional commitment from UCLA for microscope operating expenses.