Center for Ultrastructural Studies of Infectious Pathogens (CUSIP)

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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.