West/Midwest Consortium for High-Resolution Cryo Electron Microscopy

西部/中西部高分辨率冷冻电子显微镜联盟

• 批准号: 9000594
• 负责人: Mavis Agbandje-Mckenna
• 金额: $ 53.9万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-11 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9000594
• 关键词: Alabama; Biochemistry; Biological; Biology; Biomedical Research; California; Characteristics; Communities; Core Facility; Cryoelectron Microscopy; Data; Detection; Development; Drops; Drug Design; Electron Microscope; Electron Microscopy Facility; Electrons; Evaluation; Facility Accesses; Florida; Funding; Goals; Heavy Metals; Image; Institutes; Kansas; Laboratories; Lead; Liquid substance; Los Angeles; Macromolecular Complexes; Medical; Microbiology; Microscope; Midwestern United States; Modeling; Nitrogen; Organelles; Performance; Phase; Process; Records; Research; Research Infrastructure; Research Personnel; Reservations; Resolution; Resources; Sampling; Site; Speed; Staining method; Stains; Structure; System; Technology; Texas; Therapeutic Intervention; Time; Titan; Training; Translational Research; Transmission Electron Microscopy; United States National Institutes of Health; Universities; Vaccines; Washington; base; computerized data processing; data acquisition; design; detector; empowered; experience; improved; instrument; member; microscopic imaging; movie; nanometer; nanosystems; novel; novel therapeutics; operation; public health relevance; virology

 DESCRIPTION (provided by applicant): This application seeks funding to establish the West/Midwest Consortium for High-Resolution Cryo Electron Microscopy (cryoEM). The goal of the consortium is to offer 19 cryoEM users from 10 regional institutes free access to a high-end cryoEM facility with proven high-resolution capabilities located in the California NanoSystems Institute (CNSI) at University of California, Los Angeles (UCLA). UCLA will act as host institute and provide investigators in these cryoEM laboratories access to its highly productive Titan Krios cryo electron microscope recently upgraded with a Volta phase plate, a Gatan imaging filter (GIF), and pre- and post-GIF direct electron detectors. A highly experienced staff with proven records of cryoEM-derived atomic structures will provide on-site assistance to collect data and provide streamlined "movie" pre-processing for our consortium user laboratories. The critical need for this consortium for recording atomic-resolution cryoEM images of a broad range of bio-medically significant macromolecular complexes is justified by the immediate benefits to the 19 consortium users. Of particular note, we have demonstrated that, once trained by our staff, users no longer have to be present at the microscope and can remotely control the microscope and perform high-resolution cryoEM imaging after our staff have aligned the instruments for top performance, thus significantly improving accessibility to the high-end instrument. A three-member supervisory committee representing non-consortium users, regional consortium users and the UCLA facility staff will provide evaluation and approval of user projects, adding and dropping users. Under our typical operation, a user group with approved projects requests research instrument time with an existing professionally-designed online reservation system, sends cryoEM grids by overnight courier (such as FedEx) in a liquid nitrogen-cooled dry shipper, and, after their grids are loaded by our staff, image their sample remotely for 3-7 days on average, and up to 2-3 weeks if necessary. The 10 institutes are concentrated on the West coast (University of Washington in Seattle, University of California at San Diego, Scripps) and Midwest (Case Western Reserve University, Purdue University, The University of Kansas, University of Alabama at Birmingham) except for three (University of Texas at El Paso, University of Texas Medical Branch in Galveston, and University of Florida at Gainesville). With the exception of three new investigators, all these users are funded by the NIH or other federal agencies to pursue biomedical research, ranging from biology, biochemistry, virology and microbiology. The establishment of this consortium will immediately empower our users with high-resolution cryoEM capabilities for a broad range of biological samples, enabling them to understand mechanisms of action and identify new targets for the development of new therapeutics.

 描述（由申请人提供）：本申请寻求资金建立西部/中西部高分辨率冷冻电子显微镜 (cryoEM) 联盟。该联盟的目标是为来自 10 个地区机构的 19 名冷冻电子显微镜用户提供免费访问高分辨率冷冻电子显微镜的机会。位于加州大学洛杉矶分校 (UCLA) 的加州纳米系统研究所 (CNSI) 的具有经过验证的高分辨率能力的最终冷冻电镜设施将作为东道主。研究所并为这些冷冻电镜实验室的研究人员提供其高效的 Titan Krios 冷冻电子显微镜，该显微镜最近升级了 Volta 相位板、Gatan 成像滤光片 (GIF) 以及 GIF 前和后直接电子探测器。经过验证的冷冻电镜衍生原子结构记录将为我们联盟用户实验室的数据收集和简化的“电影”预处理提供现场帮助，满足该联盟对记录的迫切需求。广泛的具有生物医学意义的大分子复合物的原子分辨率冷冻电镜图像可以为 19 个联盟用户带来直接利益，特别值得注意的是，我们已经证明，一旦经过我们的员工培训，用户就不再需要在场。在我们的工作人员将仪器调整为最佳性能后，可以远程控制显微镜并执行高分辨率冷冻电镜成像，从而显着提高高端仪器的可访问性。代表非联盟的三人监督委员会。用户、区域联盟用户和加州大学洛杉矶分校设施工作人员将提供用户项目的评估和批准，添加和删除用户在我们的典型操作下，拥有批准项目的用户组通过现有的专业设计的在线预订系统请求研究仪器时间，发送。通过隔夜快递（例如联邦快递）将冷冻电镜网格放置在液氮冷却的干式运输机中，并且在我们的工作人员加载网格后，对样品进行远程成像，平均时间为 3-7 天，如果情况长达 2-3 周，这10所学院集中在西海岸（西雅图的华盛顿大学、圣地亚哥的加州大学斯克里普斯分校）和中西部（凯斯西储大学、普渡大学、堪萨斯大学、阿拉巴马大学伯明翰分校）。三个（德克萨斯大学埃尔帕索分校、德克萨斯大学加尔维斯顿医学分校和佛罗里达大学盖恩斯维尔分校）除了三名新研究人员外，所有这些用户均由 NIH 或其他联邦机构资助进行生物医学研究。 , 测距该联盟的成立将立即为我们的用户提供针对各种生物样品的高分辨率冷冻电镜功能，使他们能够了解作用机制并确定开发新疗法的新靶标。 。