Cryo-EM for the Midwest Region

Abstract Cryogenic-electron microscopy (cryo-EM) for single particle analysis has taken the fields of biological sciences and structural biology by storm, leading to breakthroughs in our understanding of many key biological processes. Cryo-EM has emerged as the primary approach for macromolecular structure determination to

visualize large protein assemblies that are not amenable to conventional structural biology approaches (e.g., NMR and X-ray crystallography). Unfortunately, researchers in Kansas do not have direct access to cryo-EM instruments at their institutions and regional access is severely limited. Therefore, many eligible investigators

have not pursued cryo-EM, and ones that have are often dependent on distant cryo-EM facilities and/or busy NIH supported national centers. When considering that iterative sample preparation optimization is required, the absence of local cryo-EM poses significant barriers for regional scientists wishing to utilize this technology.

This challenge facing Kansas investigators is emblematic of that facing investigators in other IDeA-designated states where cryo-EM is markedly underrepresented. Our plan is to establish a Midwest regional cryo-EM facility to meet needs of researchers in Kansas, Nebraska, Iowa, and beyond. We request funds for a Glacios

200 kV cryo-TEM equipped with the Falcon 4i Detector and a Selectris energy filter. The University of Kansas Medical Center executed a no-obligation-to-buy lease agreement with Thermo Fisher for installation of the Glacios system to satisfy the immediate needs of 12 major users and 7 minor users. Significant institutional

resources have been committed to this project including financial investments, infrastructure renovations, facility staff support, and programs to raise awareness and promote preliminary data acquisition. The 200 kV Glacios with the Falcon 4i and Selectris imaging filter is an ideal cryo-EM platform with a proven track record.

This system will not only provide excellent screening abilities for high-resolution analysis at NIH supported cryo-EM national facilities, but also will serve as a stand-alone instrument for single particle analysis for medium to high-resolution structures. In this way, the system will serve multiple functions and maximize the

benefits to the region. It will integrate into existing structural biology infrastructure and strengths of the region. KUMC’s proximity to multiple institutions with users needing cryo-EM including KU, Wichita State, Kansas State University, Stowers Institute for Medical Research, Creighton University, and the University of Iowa,

make it an ideal location to serve a large number of regional users. S10 support for the KUMC Glacios will meaningfully advance a sizable number of regional research programs while synergizing with national centers to improve overall workflow in meeting the needs of NIH-funded research in the US.