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

蒙大拿州立大学和合作机构获得了一项奖励，以支持购买新的200kV低温电子显微镜系统。在过去的十年里，冷冻电子显微镜（cryo-EM）发生了一场革命。随着频率的增加，单颗粒分析（SPA）提供了与x射线晶体学相当的分辨率的低温电镜图，从而产生了越来越多的大分子组合的原子模型-核糖体，转录复合物，蛋白酶体，病毒，整体膜蛋白和CRISPR/Cas靶向复合物-所有这些都直接来自低温电镜数据。低温电子断层扫描（CET）现在可以提供2-5纳米分辨率的细胞结构3D图像，在有利的情况下可以达到亚纳米分辨率。新的多用户200千伏低温电子显微镜将服务于蒙大拿州和周边各州的区域细胞和分子生命科学界。新系统将立即使蒙大拿大学系统（UM和MSU）内两个不同校区的至少5个不同部门的调查人员以及五个州地区机构的调查人员受益。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发展现代冷冻电镜技术的专业知识。最后，它将极大地加强K-12教师教育和外展项目，包括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，以及通过密歇根州立大学的MAP和通往学士学位课程的桥梁项目向蒙大拿州部落学院外展。低温电镜技术的最新进展允许用SPA在原子水平上模拟大分子复合物的结构，并在原生细胞环境中用CET观察这些结构。SPA和CET结合起来，对细胞机制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经开始对CRISPR/Cas靶向复合物、g蛋白偶联受体信号通路、生命“第三域”的古细菌病毒、新世界出血性病毒以及哺乳动物和致病菌中的铁转运进行低温电镜研究。位于北落基山脉地区的新200千伏低温电镜将以超高分辨率对大分子和细胞结构进行开创性的研究。这些研究的数据和分析将发表在同行评议的科学期刊上，在科学会议上提出，并用于教育和公共宣传活动。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.