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

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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.