Cancer initiation, progression and metastasis are caused by changes in protein machines that control core cellular processes. Cryo-electron microscopy (cryo-EM) is a powerful technology that can reveal three-dimensional pictures of these machines-the spatial arrangements of their atoms-explaining how they function normally and are defective in cancer. This information is essential to understanding the mechanisms that drive cancer, identifying drug targets, and developing therapeutics. Leveraging the current CPRIT grant, UTSW built the leading cryo-EM facility in the central United States. Since 2017 the facility has generated a huge body of cutting-edge research (69 publications) on some of ...

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Cancer initiation, progression and metastasis are caused by changes in protein machines that control core cellular processes. Cryo-electron microscopy (cryo-EM) is a powerful technology that can reveal three-dimensional pictures of these machines-the spatial arrangements of their atoms-explaining how they function normally and are defective in cancer. This information is essential to understanding the mechanisms that drive cancer, identifying drug targets, and developing therapeutics. Leveraging the current CPRIT grant, UTSW built the leading cryo-EM facility in the central United States. Since 2017 the facility has generated a huge body of cutting-edge research (69 publications) on some of the most important protein machines in cancer biology and cancer therapeutics, explaining their functions in health and disease and suggesting new therapeutic strategies. Facility programs have trained >150 young scientists in cryo-EM. Through this renewal, the facility will advance to new heights in efficiency, technology and reach, taking cancer research in Texas in new directions. We will use new hardware and software to accelerate the acquisition and analysis of cryo-EM data, speeding discovery and allowing protein machines to be studied in finer detail. We will implement microED, a new cryo-EM technology that enables chemists to create organic compounds more efficiently, accelerating development of new drugs. We will develop novel workflows integrating several state-of-the-art technologies to visualize protein machines in cell-like biochemical systems, cancer cell lines, animal tissues and patient-derived cancer tissues. These approaches will yield unprecedented information on protein structure in native environments, revealing molecular and cellular defects in cancer and suggesting new drug targets. Finally, we will increase education, training, and service to include these new technologies and extend them to scientists across Texas, advancing cancer research state-wide.

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