NIEHS Cryo-EM Core Facility

NIEHS Cryo-EM Core继续领导该地区的部署并促进冷冻电子显微镜技术的采用。于二零二三财政年度，在高影响力期刊发表的十多篇同行评审文章清楚表明。核心在应对COVID-19大流行的内部反应中发挥了重要作用，有几篇经过审查的出版物描述了针对SARS-CoV-2的潜在药理学靶点或试剂。许多合作为理解疾病和治疗的结构基础做出了重要贡献。核心解决的这些疾病相关结构涉及线粒体遗传疾病、帕金森和痴呆、抗癌药物递送系统、抗菌药物耐药性。其他结构参与基本的生物过程，如疼痛，冷和热的感觉，代谢途径和细胞应激反应。 核心受益于与分子显微镜组的密切合作，以开发增强技术能力的方法。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。

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.