Thermo Scientific Glacios cryo-TEM

Thermo Scientific Glacios 冷冻透射电镜

• 批准号: 10175401
• 负责人: Terunaga Nakagawa
• 金额: $ 200万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2022-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10175401
• 关键词: Acceleration; Anabolism; Architecture; Arts; Bacteria; Biological; Biomedical Engineering; Calcium Signaling; Cells; Chemistry; Clostridium difficile; Collaborations; Cryo-electron tomography; Cryoelectron Microscopy; Crystallization; DNA Repair; DNA biosynthesis; Discipline; Disease; Electron Microscope; Engineering; Floor; Funding; Genome; Human; In Situ; Inflammatory; Investigation; Ion Channel; Ions; Laboratories; Ligands; Link; Lipids; Macromolecular Complexes; Maintenance; Mediating; Membrane; Membrane Proteins; Messenger RNA; Micro Electron Diffraction; Minor; Molecular; Molecular Conformation; Molecular Motors; Molecular Weight; Nuclear; Output; Pathology; Pharmaceutical Preparations; Physiology; Proteins; Records; Research; Research Personnel; Research Project Grants; Resolution; Resource Sharing; Schools; Science; Signal Transduction; Specimen; Structural Biologist; Structure; Synapses; Synaptic Transmission; Synaptic Vesicles; Synaptic plasticity; Technology; Therapeutic; Toxin; United States National Institutes of Health; Vesicle; Virus Assembly; college; design; instrument; interest; medical schools; novel; particle; protein function; small molecule; structural biology; trafficking; transmission process; voltage

PROJECT SUMMARY We propose to acquire a Thermo Scientific Glacios, a 200kV cryo-transmission electron microscope, to advance our biological investigation using the growing technologies of cryo-EM. The Glacios will be a part of the Cryo-EM Facility, a shared resource of the Center for Structural Biology. Our investigators have established records of using single particle analysis and discovering novel biological molecular mechanisms at the atomic level. The addition of the Glacios will be essential for our investigators to further advance their research beyond what is currently possible using our existing instruments. Specifically, the Glacios will be essential for: (1) structural analyses of low molecular weight proteins utilizing 200kV acceleration voltage, (2) the MicroED approach that uses electron diffraction of micro-crystals, (3) investigation of macromolecular complexes in situ using cryo- electron tomography, and (4) specimen optimization to advance our efficiency to resolve at high- resolution fine conformational varieties and small molecules, such as ligands, drugs, and ions. The technology provided by the Glacios is essential for breaking new ground on the NIH-funded research projects of the major users, which include studies of synaptic transmission and plasticity (Nakagawa), in situ synapse architecture and synaptic vesicle fusion (Zhou), Clostridioides difficile toxin pathology (Lacy), nuclear mRNA transport (Ren), DNA replication and repair (Eichmann), calcium signaling (Karakas), in situ viral assembly and architectures (Wan), vesicle and membrane trafficking (Jackson), and bacterial signaling (Iverson). Additionally, 11 minor users plan to exploit the Glacios to investigate critical biological questions in membrane protein function, inflammatory signaling, genome maintenance, bacteria-host interactions, ion channel mediated signaling, lipid signaling and biosynthesis, and molecular motors. The outputs of the research projects that will use the Glacios will substantially advance our basic understanding on the mechanisms of human physiology, pathology, and disease therapeutics. The Glacios will initially be used by structural biologists and cell biologists, with the userbase predicted to extend into the fields of chemistry and bioengineering who have related scientific interests. In fact, the Glacios will be housed in the Engineering and Science Building, which is designed to nurture collaborations between disciplines via a three-floor, integrative, and collaborative laboratory space linking the School of Medicine, College of Arts and Sciences, and the School of Engineering.

项目概要 我们建议购买 Thermo Scientific Glacios，一款 200kV 低温透射电子显微镜， 利用不断发展的冷冻电镜技术推进我们的生物学研究。格拉西奥斯将 冷冻电镜设施的一部分，是结构生物学中心的共享资源。我们的 研究人员已经建立了使用单粒子分析和发现新颖物质的记录 原子水平的生物分子机制。 Glacios 的加入对于 我们的研究人员利用我们的技术进一步推进他们的研究，超越目前可能的范围 现有文书。具体而言，Glacios 对于以下方面至关重要：(1) 低结构分析 利用 200kV 加速电压测量分子量蛋白质，(2) 使用 MicroED 方法 微晶体的电子衍射，(3) 使用低温原位研究大分子复合物 电子断层扫描，以及（4）样本优化，以提高我们解决高通量问题的效率 分辨率精细构象品种和小分子，如配体、药物和离子。这 Glacios 提供的技术对于 NIH 资助的研究取得新突破至关重要 主要用户的项目，包括突触传递和可塑性的研究（中川）， 原位突触结构和突触小泡融合（周），艰难梭菌毒素病理学 (Lacy)、核 mRNA 运输 (Ren)、DNA 复制和修复 (Eichmann)、钙信号传导 (Karakas)、原位病毒组装和结构 (Wan)、囊泡和膜运输 （杰克逊）和细菌信号传导（艾弗森）。此外，11 名未成年用户计划利用 Glacios 来 研究膜蛋白功能、炎症信号、基因组等关键生物学问题 维持、细菌-宿主相互作用、离子通道介导的信号传导、脂质信号传导和 生物合成和分子马达。使用 Glacios 的研究项目的成果将 大大提高我们对人体生理、病理机制的基本认识， 和疾病治疗。 Glacios 最初将由结构生物学家和细胞生物学家使用， 用户群预计将扩展到化学和生物工程领域 相关的科学兴趣。事实上，Glacios 将坐落在工程与科学大楼内， 它旨在通过三层楼的综合性和 连接医学院、艺术与科学学院和 工程学院。