NIEHS Cryo-EM Core Facility

在2020财年期间，Cryo-EM Core继续通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二十多次合作产生的出版物数量上。今年，我们举办了由NIEHS、杜克大学和北卡罗来纳大学举办的第一次低温EM区域研讨会。研讨会有超过20位讲者出席，并有超过100名本地科学家出席。专题讨论会上介绍的大部分工作是在分子显微镜联合会的背景下与核心人员合作进行的。 在新冠肺炎大流行开始时，我们一直在积极与杜克人类疫苗研究所的Priyamvada Acharya博士和美国国立卫生研究院弗雷德里克分校的Eric Freed博士合作，解决涉及艾滋病毒主要病毒抗原--包膜糖蛋白Env的各种结构性问题。作为回应，我们迅速改变了我们的结构病毒学管道的用途，以研究类似SARS-CoV-2的S蛋白。这促使了IRP中的更多合作，其中最引人注目的是绘制NCATS马特·霍尔博士团队开发的纳米体结合位点的努力。我们还与NIEHS的其他人合作，解决了各种SARS-CoV-2非结构蛋白的结构问题。 冷冻-EM核心的合作也在NIH的内部计划中得到了发展。除了与NCI的同事正在进行的工作外，在2020财年上半年，我们还与其他IC讨论了一系列预期的合作项目。其中包括利用当前的单粒子低温电磁技术，以及发展低温电子断层扫描和原位结构测定的新能力。这些互动导致了NIEHS、NCATS、NIA、NIBIB和NIDA之间的内部财团的组织，以购买一台最先进的300keV TFS Titan Krios冷冻电子显微镜，预计将于2021年春季在NIEHS投入使用。

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.