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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：
10925019
负责人：
Mario Borgnia
金额：
$ 278.18万
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/10925019
关键词：
2019-nCoV Acceleration Adoption Antineoplastic Agents Bacterial Drug Resistance Biological Process COVID-19 pandemic Cells Cellular Stress Collaborations Complex Computer software Core Facility Cryoelectron Microscopy Crystallization Data Data Collection Dementia Deposition Disease Drug Delivery Systems Electron Microscope Electron Microscopy Engineering Ensure Equipment Genetic Goals In Situ Ions Journals Macromolecular Complexes Membrane Proteins Metabolic Pathway Methods Microscopy Mission Mitochondria Molecular Molecular Structure National Institute of Environmental Health Sciences Nuclear Magnetic Resonance Pain Parkinson Disease Peer Review Play Preparation Process Publications Reagent Research Resolution Robotics Role Sampling Scanning Specimen Structural Biologist Structure Techniques Time Training X-Ray Crystallography collaborative environment cryogenics image processing improved instrument macromolecule method development new technology novel strategies particle pharmacologic 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 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.

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。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Correction: Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies.

修正：中和引导的 HIV-1 包膜三聚体设计，对 CH235 谱系 CD4b 广泛中和抗体的未突变共同祖先具有高亲和力。

DOI：
10.1371/journal.ppat.1008200
发表时间：
2019
期刊：
PLoS pathogens
影响因子：
6.7
作者：
LaBranche,CeliaC;Henderson,Rory;Hsu,Allen;Behrens,Shay;Chen,Xuejun;Zhou,Tongqing;Wiehe,Kevin;Saunders,KevinO;Alam,SMunir;Bonsignori,Mattia;Borgnia,MarioJ;Sattentau,QuentinJ;Eaton,Amanda;Greene,Kelli;Gao,Hongmei;Liao,Hua
通讯作者：
Liao,Hua

Cryo-EM structures of the SARS-CoV-2 endoribonuclease Nsp15 reveal insight into nuclease specificity and dynamics.

DOI：
10.1038/s41467-020-20608-z
发表时间：
2021-01-27
期刊：
Nature communications
影响因子：
16.6
作者：
Pillon MC;Frazier MN;Dillard LB;Williams JG;Kocaman S;Krahn JM;Perera L;Hayne CK;Gordon J;Stewart ZD;Sobhany M;Deterding LJ;Hsu AL;Dandey VP;Borgnia MJ;Stanley RE
通讯作者：
Stanley RE

Cryo-EM reveals the architecture of the PELP1-WDR18 molecular scaffold.

DOI：
10.1038/s41467-022-34610-0
发表时间：
2022-11-09
期刊：
NATURE COMMUNICATIONS
影响因子：
16.6
作者：
Gordon, Jacob;Chapus, Fleur L.;Viverette, Elizabeth G.;Williams, Jason G.;Deterding, Leesa J.;Krahn, Juno M.;Borgnia, Mario J.;Rodriguez, Joseph;Warren, Alan J.;Stanley, Robin E.
通讯作者：
Stanley, Robin E.

Characterization of SARS2 Nsp15 nuclease activity reveals it's mad about U.

DOI：
10.1093/nar/gkab719
发表时间：
2021-09-27
期刊：
Nucleic acids research
影响因子：
14.9
作者：
Frazier MN;Dillard LB;Krahn JM;Perera L;Williams JG;Wilson IM;Stewart ZD;Pillon MC;Deterding LJ;Borgnia MJ;Stanley RE
通讯作者：
Stanley RE

Structures of AAA protein translocase Bcs1 suggest translocation mechanism of a folded protein.