Cryo-TEM for Biomedical Research

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Summary Brown University requests support for a Tundra Cryo-Transmission Electron Microscope (Cryo-TEM). This microscope will be used to examine protein structure by single particle analysis for a better basic understanding of biochemical processes in health and disease. Vitrified samples imaged on the Tundra Cryo-TEM can be recovered for cryo-electron microscopy (cryo-EM) at high resolution in national cryo-EM centers. In addition, the requested microscope will be used as a standard TEM for imaging small vesicles, organelles and neural connections in ultrathin tissue sections. The Tundra Cryo-TEM will replace a 39-year-old TEM in the Division of Biology and Medicine and will be the first Cryo-TEM capable of single particle analysis in the State of Rhode Island. The Cryo-TEM will be used immediately by 16 investigators. Collectively, these 16 user groups are funded by 31 NIH grants, covering a broad area in biomedical research ranging from antibiotic resistance and infertility to aging and neurodegenerative disease. All major users have a substantial need for cryo-EM. These major users either traveled out of state for cryo-EM or used other technologies that left questions unanswered, especially when studying large dynamic proteins. The minor users plan to use the requested microscope as a standard TEM or have cryo-EM projects that were put on hold since the required equipment has not been available at Brown University. All major and minor users have research projects that would immediately benefit from the proposed equipment. The impact of the proposed imaging system will extend beyond the projects of the major and minor users, since the microscope will be made be made available to the broader scientific community in Rhode Island, which has over 700 active NIH-funded projects. The microscope will be set up in the Leduc Bioimaging Facility, which has the technical expertise to maintain the instrument and train its users. In addition, biochemical sample optimization and evaluation will be supported by Brown University’s Structural Biology Facility and data storage and analysis will be supported by the Center for Computation and Visualization. The Leduc Bioimaging Facility has a broadly-based Advisory Committee, an excellent track record maintaining various high-end imaging systems, and strong institutional support, which guarantees that the instrumentation will be used to its maximum potential for years to come.