Acquisition of 200 kV Glacios Cryo-TEM at the University of Iowa

PROJECT SUMMARY/ABSTRACT This S10 proposal is for the purchase of a modern transmission cryogenic electron microscope (cryo- EM) to advance biomedical research at the University of Iowa. The instrument will be housed in a central location easily accessible by all university research groups. The cryo-EM instrument will be integrated into the Carver College of Medicine Protein and Crystallography Facility (PCF) that has provided researchers access and training in cryo-EM, X-ray crystallography, and additional techniques for a combined 15+ years. Through institutional investments in PCF staff training, computational resources, new faculty hires, and ancillary cryo-EM equipment, the PCF has established a workflow and provided expertise for cryo-EM structure determination. However, there is no dedicated cryo-EM instrument at Iowa to screen sample quality or determine high-resolution macromolecular structures. Thus, rapid optimization of samples and collection of datasets for cryo-EM structure determination is not possible and has a substantial negative impact on timely research project progression for numerous investigators. The acquisition of a Thermo Scientific Glacios Cryo-TEM instrument would overcome these limitations and transform the ability of University of Iowa researchers by completing our local workflow and eliminating the sample optimization bottleneck. This will increase research output by collecting high- quality data on the Glacios and only using the National Cryo-EM Centers for select samples that require Krios data collection. The proposed used Glacios microscope offers significant cost savings over the same configuration on a new instrument. It has a user-friendly software interface, high sample throughput, automated tasks, AI-optimized data collection, and high-resolution data collection which makes it the ideal single particle cryo-EM instrument for our user community. Structure determination by our investigators would enhance a diverse collection of NIH-funded projects that address biomedical research questions in areas such as ion channel function, eukaryotic and prokaryotic signal transduction, DNA repair, vision, membrane transport, cancer therapeutics, viruses, and drug delivery systems. Structural studies in these areas will also provide substantial training opportunities for students and postdoctoral scientists that will add to the core group of independent instrument users. The proposed Glacios cryo-EM will significantly impact biomedical research at the University of Iowa by increasing research productivity, enhancing scientific collaboration, boosting research grant competitiveness, and advancing efforts to attract new investigators and students.