High-resolution low-cost 100 kV electron cryogenic microscope for near-atomic protein structure determination.

Structures of proteins, nucleic acids, and their complexes constitute the basis for understanding the mechanisms of biological processes on a molecular level. They accelerate drug design and biotechnological applications. During the last decade, three-dimensional cryogenic electron microscopy has emerged as the primary method for determining high-resolution structures of proteins to near-atomic resolution. This includes pharmaceutically relevant human proteins and pathogens. We pioneered high-resolution cryo-EM in Belgium by setting up VIB-VUB Center for Biological Electron Cryogenic Microscopy (BECM) in 2017, attracting researchers from the whole of Belgium along with numerous European and industrial users. However powerful, cryo-EM is an expensive technique due to the high costs of electron microscopes. Recent research showed that 1) 100 kV rather than 300 kV electron microscopes are more suitable for routine structure determination using single particle cryo-EM, and 2) 100 kV microscopes with direct electron detector (DED) and Field Emission Gun (FEG) can be nearly an order of magnitude cheaper. Within this project, our aim is to purchase and build a 100 kV electron microscope on the basis of a JEOL JEM-1400 microscope equipped with FEG and DED. The microscope will allow users to screen their cryo-EM samples and determine the structures of proteins within a few hours. It will be accessible for hourly costs similar to low-resolution screening microscopes.