Abstract The Southeastern Center for Microscopy of MacroMolecular Machines (SECM4), at Florida State University (FSU) will be a service center that will enable sample preparation and cryogenic electron microscopy (cryo-EM) imaging of specimens for high-resolution biomolecular structure determination. The center will be led by Dr. Scott Stagg and Dr. Kenneth Taylor and will feature two staff members with complimentary expertise. This will be the second generation of the SECM4. The first generation provided high-resolution cryo-EM data collection for cryo-EM experts. In the new generation of the SECM4, we are expanding the scope of the resource by offsetting the cost of collecting high-resolution data on the microscope for all users with a very modest usage fee and also by offering a large number of new services including cryo-EM specimen optimization, specimen preparation, specimen screening, high-resolution data collection, routine single particle data analysis, and training for all aspects of cryo- EM from specimen preparation to processing. We will target users in the greater Southeast to be clients for the center, specifically focusing expanding into the underserved IDeA states that have not benefitted from the current explosion in cryo-EM due to the extraordinary costs that serve as an entry barrier. Our approach will enable exceptional economies of scale because we will: 1) enable users at universities across the Southeast to gain entry the cryo-EM field without making multi-million dollar investments in instrumentation, 2) by offering screening and specimen optimization services, we will address the biggest bottleneck in cryo-EM right now, which is preparation of cryo-EM samples that will reconstruct to high-resolution, 3) by offering in person training and offsetting the travel costs, we will enable interested users to gain entry into the field of cryo-EM without having to seek out a collaboration with an already saturated cryo-EM expert.