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

基本信息

批准号：
9752575
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
项目类别：
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/9752575
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 Research Personnel 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 public health relevance remote control virology

项目摘要

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（由应用程序提供）：本申请寻求资金建立高分辨率冷冻电子显微镜（Cryoem）的西/中西部财团。该财团的目的是为10个区域学院的199个冷冻用户免费访问高端冷冻设施，并在加利福尼亚大学加利福尼亚大学洛杉矶分校（UCLA）的加利福尼亚纳米系统研究所（CNSI）中有经过验证的高分辨率能力。加州大学洛杉矶分校（UCLA）将充当主机研究所，并在这些冷冻实验室中为研究人员提供了最近使用Volta相板，GATAN成像过滤器（GIF）以及GIF前和GIF后直接电子检测器升级的高生产力的Titan Krios Cryo Electron显微镜。经验丰富的员工，具有批准的冷冻原子结构记录，将提供现场帮助，以收集数据并为我们的财团用户实验室提供简化的“电影”预处理。该财团对记录广泛的生物 - 密歇根大分子分子复合物的原子分辨率冷冻图像的关键需求证明了19个财团使用者的直接利益是合理的。尤其值得注意的是，我们已经证明，一旦受过我们的员工培训，用户不再需要在显微镜上出现，并且可以远程控制显微镜并在我们的员工将仪器与最佳性能保持一致之后，从而显着提高了对高端仪器的可访问性。代表非信徒用户，区域财团用户和UCLA工厂工作人员的三名成员的监督委员会将提供对用户项目的评估和批准，从而增加和删除用户。在我们典型的操作下，拥有批准项目的用户组要求使用现有专业设计的在线预订系统进行研究工具时间，并在液态氮气冷却的干式托运机中通过夜间快递（例如FedEx）发送冷冻电网，并且在我们的员工将其段落置于3-7天之后，平均为3-7天，并在2-3周内进行远程图像。这10个机构集中在西海岸（西雅图的华盛顿大学，加利福尼亚大学圣地亚哥分校，斯克里普斯，斯克里普斯）和中西部（Case Western Reserve University，Purdue University，Purdue University，Purdue University，Purdue University，堪萨斯州，堪萨斯州伯明翰大学），除三个（得克萨斯大学德克萨斯大学，德克萨斯大学，德克萨斯大学，德克萨斯大学，德克萨斯大学，德克萨斯大学的埃尔帕索分校，德克萨斯大学，弗洛斯维尔大学的加尔维斯顿大学医学院）。除三个新调查人员外，所有这些用户都是由NIH或其他联邦机构资助的，以从事生物医学研究，包括生物学，生物化学，病毒学和微生物学。该财团的建立将立即为我们的用户提供高分辨率的冷冻功能，以提供广泛的生物样本，使他们能够了解行动机制并确定开发新疗法的新目标。