Cryo Transmission Electron Microscope for SPA, Cryo-ET and MicroED studies at UCSB

项目总结/摘要 通过购买GlaciosTM透射电子显微镜系统，我们试图建立第一个单粒子 分析（SPA）、低温电子显微镜（cryo-EM）、电子断层扫描（-ET）和微电子衍射（micro-electron diffraction）。 艾德）设施，以及加州中央海岸唯一的一个：UCSB 结构生物学冷冻电子显微镜（SB 2 EM）设施。专用的生物冷冻EM能力将成为 关键UCSB的强大的领导和力量在定量生物学，结构生物化学和生物工程在 跨学科界面没有什么地方是部门之间的界限，学院和程序比在渗透 UCSB：教师建议所有科学和工程系的博士生没有到很少的障碍，双重任命 在一个以上的部门是UCSB和研究业务的规范依赖于高端和最先进的 在专业运行的共享设施的仪器是UCSB校园的强项。SB 2 EM设施将被整合 这种跨学科合作的文化，以及一流的共享设施和实验室网络， 我们校园里的科学和工程界基本上是融合在一起的。SB 2 EM对当前NIH资助的UCSB的影响 教师将是直接的，即时的和戏剧性的，但它也将远远超出目前资助的NIH项目，通过激励 并使生物医学启发的研究的全新领域成为可能，并雇用新的教师人才。 “打开灯”直接看到生命分子机制的能力从根本上改变了我们 理解并最终操纵生物材料、系统和过程。Cryo-EM将原子和分子 水平的信息，通常是化学家的核心方法，进入生物学和生物工程，反之亦然，通过， 例如，分子伴侣如何解开神经元斑块的可视化，或者通过基于结构的 分子抑制剂的工程化以及由蛋白质和核酸构建块构建的结构。的出现 对生物分子和系统的前所未有的高分辨率结构洞察提供了一个关键的竞争优势。 有利于了解它们的功能，发现功能驱动机制，并工程治疗 解决方案蛋白质功能的研究将大大促进生物系统的重新设计， 随着对底层结构和结构特征的了解而大大增强。正是这种洞察力让我们 优先考虑UCSB的基于结构的生物化学，生物有机化学，生物学和生物工程。

PROJECT SUMMARY/ABSTRACT With the purchase of a GlaciosTM transmission electron microscope system we seek to establish the first single particle analysis (SPA) cryo-electron microscopy (cryo-EM), -electron tomography (-ET) and micro-electron diffraction (micro- ED) facility at the University of California Santa Barbara, and the only one on the California Central Coast: the UCSB Structural Biology cryo-Electron Microscopy (SB2EM) facility. Dedicated biological cryo-EM capabilities will become the linchpin to UCSB’s strong leadership and strength in quantitative biology, structural biochemistry and bioengineering at the interdisciplinary interface. Nowhere is the boundary between Departments, Colleges and Programs more permeable than at UCSB: faculty advise PhD students of all Science and Engineering Departments with no to little barriers, dual appointments in more than one department is the norm at UCSB and research operations relying on high-end and state-of-the-art instrumentation in professionally run shared facilities is a forte of the UCSB campus. The SB2EM facility will be integrated into this culture of interdisciplinary collaboration, as well as a network of first-rate shared facilities and laboratories across our campus’s largely merged science and engineering community. The impact of SB2EM on the current NIH funded UCSB faculty will be direct, immediate and dramatic, but it will also go well beyond the currently funded NIH projects by inspiring and enabling entirely new areas of biomedically inspired research, and the hiring of new faculty talent. The ability to the “turn the lights on” to directly see the molecular machinery of life fundamentally changes how we understand and, ultimately, manipulate biological materials, systems and processes. Cryo-EM brings atomic- and molecular- level information, typically the core approach of a chemist, into biology and bioengineering, and vice versa, through, for example, the visualization of how molecular chaperones untangle neurofibrillary plaques, or through the structure-based engineering of molecular inhibitors and architectures built of protein and nucleic acid building blocks. The emergence of unprecedentedly high-resolution structural insights into biological molecules and systems offers a critical competitive advantage towards understanding their functions, discovering function-driving mechanisms, and engineering therapeutic solutions. The study of the protein function will be dramatically facilitated and the re-engineering of biological systems vastly enhanced with knowledge of the underlying structure and structural characteristics. It is this insight that led us to prioritize structure-based biochemistry, bioorganic chemistry, biology, and bioengineering at UCSB.