NIEHS Cryo-EM Core Facility

NIEHS 冷冻电镜核心设施

• 批准号: 10253948
• 负责人: Mario Borgnia
• 金额: $ 290.47万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 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/10253948
• 关键词: 2019-nCoV; Binding Sites; COVID-19 pandemic; Collaborations; Complex; Core Facility; Cryo-electron tomography; Cryoelectron Microscopy; Crystallization; Development; Electron Microscope; Electron Microscopy; Ensure; Goals; HIV Antigens; Human; Human Resources; In Situ; Institutes; Intramural Research Program; Macromolecular Complexes; Maps; Membrane Proteins; Methods; Microscopy; Mission; Molecular; Molecular Structure; National Institute of Biomedical Imaging and Bioengineering; National Institute of Drug Abuse; National Institute of Environmental Health Sciences; Nonstructural Protein; Nuclear Magnetic Resonance; Preparation; Process; Productivity; Proteins; Publications; Research; Research Personnel; Resolution; Scientist; Series; Specimen; Structural Biologist; Structure; Techniques; Technology; Titan; Training; United States National Institutes of Health; Vaccines; Viral Antigens; Work; X-Ray Crystallography; collaborative environment; env Glycoproteins; image processing; macromolecule; nanobodies; new technology; novel strategies; particle; prospective; response; structural biology; symposium; tool; virology

During FY2020, the Cryo-EM Core continued to collaborate with regional researchers through the Molecular Microscopy Consortium. The high productivity of the past year is reflected in the number of publications that resulted from over two dozen collaborations. This year we had our first Regional Symposium in cryo-EM organized by NIEHS, Duke and UNC. The symposium featured over 20 speakers and was attended by over 100 local scientists. Most of the work presented in the symposium was performed in collaboration with Core personnel in the context of the Molecular Microscopy Consortium. At the onset of the COVID-19 pandemic, we had been actively collaborating with Dr. Priyamvada Acharya at the Duke Human Vaccine Institute and with Dr. Eric Freed at NCI-Frederick on various structural questions involving the main viral antigen of HIV, the envelope glycoprotein Env. In response, we rapidly repurposed our structural virology pipelines to study the analogous SARS-CoV-2 S-protein. This prompted additional collaborations in the IRP, most notably an effort to map the binding sites of nanobodies developed by the group of Dr. Matt Hall at NCATS. We are also collaborating with others at NIEHS to solve the structure of a variety of SARS-CoV-2 non-structural proteins. The collaborations of the Cryo-EM Core have also grown in the NIH Intramural Program. In addition to ongoing work with colleagues at NCI, through the first half of FY2020 we have discussed a series of prospective collaborative projects with other ICs. These include both providing access to current technologies in single particle cryo-EM as well as the development of new capabilities in cryo-electron tomography and in situ structure determination. The interactions led to the organization of an intramural consortium between NIEHS, NCATS, NIA, NIBIB and NIDA for the purchase of a state of the art 300 keV TFS Titan Krios cryo-electron microscope which is expected to be operational at NIEHS by the spring of 2021.

于二零二零财政年度，Cryo-EM Core继续透过分子显微镜联盟与区域研究人员合作。过去一年的高生产率反映在20多项合作产生的出版物数量上。今年，我们举办了由NIEHS、杜克和麻省理工学院组织的第一次冷冻EM区域研讨会。研讨会有20多位讲者，100多位当地科学家参加。研讨会上提出的大部分工作是与分子显微镜联盟的核心人员合作进行的。 在COVID-19大流行开始时，我们一直与杜克人类疫苗研究所的Priyamvada Acharya博士和NCI-Frederick的Eric Freed博士积极合作，研究涉及HIV主要病毒抗原包膜糖蛋白Env的各种结构问题。作为回应，我们迅速改变了我们的结构病毒学管道，以研究类似的SARS-CoV-2 S蛋白。这促使IRP进行了更多的合作，最值得注意的是NCATS的Matt Hall博士团队开发的纳米抗体结合位点的地图。我们还与NIEHS的其他人合作，以解决各种SARS-CoV-2非结构蛋白的结构。 Cryo-EM核心的合作也在NIH校内项目中得到了发展。除与NCI同事持续合作外，于二零二零财政年度上半年，我们已与其他IC讨论一系列潜在合作项目。这些包括提供单粒子cryo-EM的现有技术以及开发cryo-electron tomography和原位结构测定的新能力。这些互动导致NIEHS，NCATS，NIA，NIBIB和NIDA之间的内部联盟组织，用于购买最先进的300 keV TFS Titan Krios低温电子显微镜，预计将于2021年春季在NIEHS投入使用。