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: 9930217
• 负责人: Mavis Agbandje-Mckenna
• 金额: $ 35万
• 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/9930217
• 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; Infrastructure; Institutes; Kansas; Laboratories; Liquid substance; Los Angeles; Macromolecular Complexes; Medical; Microbiology; Microscope; Midwestern United States; Modeling; Nitrogen; Organelles; Performance; Phase; Records; Research Personnel; Research Project Grants; Reservations; Resolution; Resources; Sampling; Site; Speed; 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; data acquisition; design; detector; experience; imaging detection; improved; instrument; member; microscopic imaging; movie; nanometer resolution; nanosystems; new therapeutic target; novel therapeutics; operation; remote control; virology

Title: West/Midwest Consortium for High-Resolution Cryo Electron Microscopy Summary 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 biomedically 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 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.

标题：西部/中西部高分辨率冷冻电子显微镜联盟 概括 该申请寻求资金建立西部/中西部高分辨率冷冻电子联盟 显微镜（冷冻电镜）。该联盟的目标是为来自 10 个地区机构的 19 位冷冻电镜用户免费提供 访问位于加利福尼亚州的具有经过验证的高分辨率功能的高端冷冻电镜设施 加州大学洛杉矶分校 (UCLA) 纳米系统研究所 (CNSI)。加州大学洛杉矶分校将作为主办机构 并为这些冷冻电镜实验室的研究人员提供其高生产力的 Titan Krios 冷冻电子 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。经验丰富的员工，拥有冷冻电镜衍生原子结构的可靠记录 将提供现场协助收集数据并为我们提供简化的“电影”预处理 联盟用户实验室。该联盟迫切需要记录原子分辨率的冷冻电镜 广泛的具有生物医学意义的大分子复合物的图像通过直接的证明是合理的 惠及19家联盟用户。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， 用户不再需要在显微镜前，可以远程控制显微镜并执行 在我们的工作人员将仪器对准以获得最佳性能后，即可进行高分辨率冷冻电镜成像，从而 显着提高了高端仪器的可访问性。三人监事会 代表非联盟用户、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，一个用户组 与批准的项目研究仪器时间与现有的专业设计的在线预订 系统，通过隔夜快递（例如联邦快递）在液氮冷却的干式运输机中发送冷冻电镜网格，以及 在我们的工作人员加载他们的网格后，平均需要 3-7 天，最多 2-3 天对他们的样本进行远程成像 如果有必要的话，几周。这10所院校集中在西海岸（西雅图的华盛顿大学、 加州大学圣地亚哥分校，斯克里普斯分校）和中西部大学（凯斯西储大学，普渡大学） 大学、堪萨斯大学、阿拉巴马大学伯明翰分校），除了三所大学（University of 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 从事生物医学研究，包括生物学、生物化学、病毒学和微生物学。这 该联盟的成立将立即为我们的用户提供高分辨率冷冻电镜功能 适用于广泛的生物样本，使他们能够了解作用机制并识别新的 开发新疗法的目标。