NIEHS Cryo-EM Core Facility

NIEHS Cryo-EM核心继续在该地区领导部署和促进采用低温电子显微镜技术。2023财年在高影响力期刊上发表的十几篇同行评议文章就是一个明显的迹象。核心中心在应对新冠肺炎大流行的内部应对中发挥了重要作用，有几篇综述的出版物描述了对抗SARS-CoV-2的潜在药理靶点或试剂)。许多合作为理解疾病和治疗的结构基础做出了重要贡献。这些在核心解决的疾病相关结构涉及线粒体遗传病、帕金森和痴呆症、抗癌药物输送系统)、抗菌素耐药性。其他结构还参与基本的生物过程，如疼痛、冷和热感觉、代谢途径和对细胞应激的反应。 核心得益于与分子显微镜小组在开发提高技术能力的方法方面的密切合作。这些措施包括部署用于样品沉积和时间分辨结构确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，在原位解决大分子络合物的结构。

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 FY2023 are a clear indication. The Core has played an important role in the intramural response to the COVID-19 pandemic with several reviewed publications describing potential pharmacological targets or reagents against SARS-CoV-2). 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 diseas, Parkinson and dementia, anticancer drug delivery systems), antibacterial resistance. Other structures are involved in fundamental biological processes such as pain, cold and heat sensing, metabolic pathways, and responses to cellular stress. The Core benefits from a close collaboration with the Molecular Microscopy Group on the development of methods that enhance 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 completed 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.