Center for Ultrastructural Studies of Infectious Pathogens (CUSIP)

利用凯克和克莱堡基金会的额外赠款支持，一种独特的低温电子 具有生物安全3级(BSL3)容器的显微镜(CryoEM)中心已在 德克萨斯大学加尔维斯顿分校(UTMB)。中华医学会超微结构研究中心 传染病病原体(CUSIP)是美国第一个高密封性冷冻EM设施，旨在获得 病原微生物的高分辨率结构，包括新出现的病毒和细菌病原体。 新设施配备了两台具有远程成像功能的最先进的200kev冷冻电子显微镜 允许世界各地的微生物学家直接访问CUSIP进行数据收集和 图像处理。这一设施为研究高致病性提供了独特的研究机会 并培训年轻的微生物学家，从事开发新疫苗和生产的职业 与新出现的和热带疾病作斗争的抗菌疗法。CUSIP作为一名知识分子 核心，团结起来，帮助UTMB和全国各地的研究人员。CUSIP促进了 病毒学家、微生物学家、电子显微镜专家和 结构生物学家获取和分析感染性病原体的高分辨率结构以了解 它们的毒力和传染性的机制。 这项建议的具体目的是： 目标1.继续在UTMB的BSL3实验室开发最先进的低温EM设备，用于 研究人员发起的NIH A-C类病原体研究项目。这个设施中的基础设施 允许对高致病性病毒和其他微生物进行远程成像，为科学家提供 在全国各地都可以使用该设施。将建立博士后和博士后研究员培训 使用通过UTMB和其他机构提供的现有培训赠款。 目的2.发展实验和计算方法来确定非余面体的结构 病毒使用Cryo-EM数据。这些方法将有助于研究病原体，如 冠状病毒和高致病性流感病毒。此外，用于生成中等分辨率的软件 将开发断层摄影术来研究非对称微生物(例如细菌)和 细胞器。 目标3.扩展CUSIP服务，以包括WRCE和RCE中的大量研究人员 生物防御网。

Using additional grant support from the Keck and Kleburg Foundations, a unique cryo-electron microscopy (cryoEM) center with biosafety level 3 (BSL3) containment has been established at the University of Texas Medical Branch in Galveston (UTMB). The Center for Ultrastructural Studies of Infectious Pathogens (CUSIP) is the first high-containment cryoEM facility in the US designed to obtain high-resolution structures of pathogenic microorganisms, including emerging viral and bacterial agents. The new facility houses two state-of-the-art 200 keV cryo-electron microscopes with remote imaging capabilities that allow microbiologists worldwide to directly access the CUSIP for data collection and image processing. This facility provides unique research opportunities to study highly pathogenic microorganisms and to train young microbiologists for productive careers developing new vaccines and antimicrobial therapies to combat emerging and tropical diseases. The CUSIP serves as an intellectual core, drawing together and helping researchers at UTMB and around the country. The CUSIP promotes extensive and productive collaborations between virologists, microbiologists, electron microscopists and structural biologists to obtain and analyze high resolution structures of infectious agents to understand the mechanism of their virulence and infectivity. The specific aims of this proposal are to: Aim 1. Continue to develop a state-of-the-art cryoEM facility in a BSL3 laboratory at UTMB for investigator-initiated research projects of NIH Category A-C pathogens. The infrastructure in this facility allows for remote imaging of highly pathogenic viruses and other microorganisms that provide scientists around the country access to the facility. Training for pre- and postdoctoral fellows will be established using existing training grants available through UTMB and other institutions. Aim 2. Develop experimental and computational methodologies to determine the structures of noncosahedral viruses using cryo-EM data. These methods will be useful to study pathogens such as coronaviruses and highly pathogenic influenza viruses. In addition, software for generating mediumresolution tomograms will be developed to study non-symmetric microorganisms (e.g., bacteria) and organelles. Aim 3. Expand CUSIP services to include a large number of researchers in WRCE and in the RCE Biodefense Network.