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NIEHS Cryo-EM Core Facility

NIEHS 冷冻电镜核心设施

基本信息

批准号：
10697893
负责人：
Mario Borgnia
金额：
$ 184.26万
依托单位：
NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10697893
关键词：
2019-nCoV Adoption Antineoplastic Agents Bacterial Drug Resistance Biochemistry Biological Process COVID-19 pandemic Cells Cellular Stress Collaborations Complex Computer software Core Facility Cryoelectron Microscopy Crystallization Data Data Collection Deposition Disease Drug Delivery Systems Electron Microscope Electron Microscopy Engineering Ensure Equipment Genetic Diseases Goals In Situ Institutes Ions Journals Lead Macromolecular Complexes Membrane Proteins Metabolic Pathway Methods Microscopy Mission Mitochondria Molecular Molecular Structure National Center for Advancing Translational Sciences National Institute of Biomedical Imaging and Bioengineering National Institute of Drug Abuse National Institute of Environmental Health Sciences Nature Nuclear Magnetic Resonance Nucleic Acids Pain Parkinson&apos s Dementia Peer Review Pharmacology Play Preparation Process Publications Reagent Research Resolution Robotics Role Sampling Scanning Specimen Structural Biologist Structure Techniques Time Training United States National Institutes of Health X-Ray Crystallography collaborative environment cryogenics image processing improved instrument macromolecule method development nano new technology novel strategies particle response structural biology tool

项目摘要

The NIEHS Cryo-EM Core continues to lead the deployment and to promote the adoption of techniques in cryo-electron microscopy in the region. Over a dozen peer reviewed articles in high impact journals during FY2022 are a clear indication. The Core has played an important role in the intramural response to the COVID-19 pandemic with four peer reviewed publications describing potential pharmacological targets or reagents against SARS-CoV-2 (Hong et al. PNAS 2022, Fu et al, PloS One 2022, Frazier et al. Nucleic Acids Res. 2022, Frazier et al. Nucleic Acids Res. 2021 and Pillon et al. Nat. Commun.). Many collaborations have led to important contributions to the understanding of structural underpinnings of disease and therapy. These disease relevant structures solved at the Core involve mitochondrial genetic disease (Riccio et al. PNAS), Parkinson and dementia ( Dasari et al., Biochemistry 2022), anticancer drug delivery systems (Saha et al Nano Lett. 2022), antibacterial resistance (Travis et al. Nat. Commun. 2022). Other structures are involved in fundamental biological processes such as pain, cold and heat sensing (Kwon Nat Struct Mol Biol. 2021), metabolic pathways (Klemm et al. J Biol Chem.), and responses to cellular stress (Simoes et al. Cell Rep. 2022, Kumar et al. Nature 2022). The Core benefits from a close collaboration with the Molecular Microscopy Group on the development of methods that enhance our technical capabilities. These include deployment of in house engineered robotic equipment for sample deposition and time resolved structure determination, improved and accelerated methods for data collection, and software for in-line processing and assessment of data. This year we expanded our capabilities by deploying a 300 KeV cryo-electron microscope acquired in collaboration with NIA, NIBIB, NIDA and NCATs. This state-of-the-art instrument will provide access to high-throughput and high-resolution data collection for single particle cryo-EM to the collaborating institutes and to others at the IRP via the NIH Cryo-EM Consortium. We are also completing the deployment of a cryogenic focused ion beam scanning electron microscope (cryo-FIBSEM). This instrument will allow us to delve into the cell to solve the structure of macromolecular complexes in situ.

NIEHS Cryo-EM Core继续领导部署，并促进该地区采用冷冻电子显微镜技术。于二零二二财政年度，在高影响力期刊发表的十多篇同行评审文章清楚表明。Core在应对COVID-19大流行的内部反应中发挥了重要作用，有四篇同行评审的出版物描述了针对SARS-CoV-2的潜在药理学靶标或试剂（Hong et al. PNAS 2022，Fu et al.，PloS One 2022，Frazier et al. Nucleic Acids Res. 2022，Frazier et al. Nucleic Acids Res. 2021和Pillon et al. Nat. Commun.）。许多合作为理解疾病和治疗的结构基础做出了重要贡献。在核心解决的这些疾病相关结构涉及线粒体遗传病（Riccio等人，PNAS）、帕金森和痴呆（Dasari等人，Biochemistry 2022）、抗癌药物递送系统（Saha等人Nano Lett. 2022）、抗菌抗性（Travis等人，Nat. Commun. 2022年）。其他结构涉及基本生物过程，例如疼痛、冷和热感测（Kwon Nat Struct Mol Biol.2021）、代谢途径（Klemm等人J Biol Chem.）、和对细胞应激的反应（西莫埃et al. Cell Rep.2022，Kumar et al. Nature 2022）。核心受益于与分子显微镜组的密切合作，以开发增强我们技术能力的方法。其中包括部署用于样品沉积和时间分辨结构测定的内部工程机器人设备，改进和加速数据收集方法，以及在线处理和评估数据的软件。今年，我们通过部署与NIA，NIBIB，NIDA和NCAT合作获得的300 KeV低温电子显微镜来扩大我们的能力。这种最先进的仪器将通过NIH Cryo-EM联盟为合作机构和IRP的其他机构提供单粒子cryo-EM的高通量和高分辨率数据收集。我们还完成了低温聚焦离子束扫描电子显微镜（cryo-FIBSEM）的部署。这台仪器将使我们能够深入细胞，原位解决大分子复合物的结构。