A Multi-User Cryo-Electron Microscope for the Cellular and Molecular Life Sciences Community in the Northern Rocky Mountain Region

用于北落基山脉地区细胞和分子生命科学界的多用户冷冻电子显微镜

• 批准号: 1828765
• 负责人: Martin Lawrence
• 金额: $ 242.15万
• 依托单位: Montana State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-10-01 至 2022-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1828765&HistoricalAwards=false
• 关键词: Multi; User; Cryo; Electron; Microscope

An award is made to Montana State University and collaborating institutions to support the acquisition of a new 200kV cryo-electron microscopy system. The last decade has seen a revolution in cryo-electron microscopy (cryo-EM). With increasing frequency, single particle analysis (SPA) is providing cryo-EM maps at resolutions on par with X-ray crystallography, resulting in atomic models for a growing number of macromolecular assemblies - ribosomes, transcription complexes, proteasomes, viruses, integral membrane proteins and CRISPR/Cas targeting complexes - all directly from cryo-EM data. Cryoelectron tomography (CET) can now provide 3D images of cellular structures at 2-5 nm resolution, and in favorable cases to sub-nanometer resolution. The new multi-user 200 kV cryo-electron microscope will serve the regional cellular and molecular life sciences community in Montana and the surrounding states. The new system will immediately benefit investigators in at least 5 different departments on two different campuses within the Montana University System (UM and MSU), as well as investigators at regional institutions in a five-state area. In addition, the system will have a significant impact on undergraduate, graduate and post-doctoral education, allowing emerging scientists in the Northern Rockies to develop expertise with modern cryo-EM techniques. Finally, it will greatly enhance K-12 teacher education and outreach programs by MSUs Thermal Biology Institute, the Center for Biofilm Engineering, the Chemistry and Biochemistry REU program, and outreach to Montana's Tribal Colleges through MSU's MAP and Bridges to Baccalaureate Programs. Recent technical advances in cryo-EM allow the structures of macromolecular complexes to be modeled at the atomic level by SPA, and observation of these structures within the native cellular environment with CET. Combined, SPA and CET provide profound biological insight into the biochemical activities and mechanisms of cellular machinery. Toward this end, investigators across the Northern Rockies have initiated cryo-EM studies of CRISPR/Cas targeting complexes, G-protein coupled receptor signaling pathways, archaeal viruses in the "3rd domain" of life, new world hemorrhagic viruses, and iron transport in mammals and pathogenic bacteria. The new 200 kV cryo-EM in the Northern Rockies region will enable groundbreaking investigations of macromolecular and cellular structures at ultrahigh resolution. Data and analyses from these studies will be published in peer-reviewed scientific journals, presented at scientific meetings, and used in both educational and public outreach activities.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

蒙大拿州立大学及其合作机构获得了一项奖励，以支持购买新的 200kV 冷冻电子显微镜系统。 过去十年见证了冷冻电子显微镜 (cryo-EM) 的革命。随着频率的增加，单粒子分析 (SPA) 提供的冷冻电镜图谱的分辨率与 X 射线晶体学相当，从而为越来越多的大分子组装体（核糖体、转录复合物、蛋白酶体、病毒、整合膜蛋白和 CRISPR/Cas 靶向复合物）建立原子模型，所有这些都直接来自冷冻电镜数据。冷冻电子断层扫描 (CET) 现在可以提供 2-5 nm 分辨率的细胞结构 3D 图像，在有利的情况下可以提供亚纳米分辨率。新型多用户 200 kV 冷冻电子显微镜将为蒙大拿州及周边各州的区域细胞和分子生命科学界提供服务。新系统将立即使蒙大拿大学系统（UM 和 MSU）两个不同校区的至少 5 个不同院系的研究人员以及五个州地区的地区机构的研究人员受益。此外，该系统将对本科生、研究生和博士后教育产生重大影响，使北落基山脉的新兴科学家能够利用现代冷冻电镜技术发展专业知识。最后，它将极大地加强密歇根州立大学热生物学研究所、生物膜工程中心、化学和生物化学 REU 项目的 K-12 教师教育和外展项目，并通过密歇根州立大学的 MAP 和学士学位桥梁项目向蒙大拿州部落学院进行外展。冷冻电镜的最新技术进步允许通过 SPA 在原子水平上对大分子复合物的结构进行建模，并通过 CET 在天然细胞环境中观察这些结构。 SPA 和 CET 相结合，为细胞机器的生化活动和机制提供了深刻的生物学见解。为此，北落基山脉的研究人员已开始对 CRISPR/Cas 靶向复合物、G 蛋白偶联受体信号通路、生命“第三域”中的古菌病毒、新世界出血性病毒以及哺乳动物和病原细菌中的铁转运进行冷冻电镜研究。北落基山脉地区的新型 200 kV 冷冻电镜将能够以超高分辨率对大分子和细胞结构进行突破性研究。 这些研究的数据和分析将发表在同行评审的科学期刊上，在科学会议上展示，并用于教育和公共宣传活动。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。