Cryo-Electron Microscopy at the Frederick National Laboratory

High Resolution Cryo-EM with a model of a p97 protein

The Frederick National Laboratory houses advanced instrumentation for cryo-electron microscopy (cryo-EM) to provide cancer researchers access to the latest technology for high resolution imaging of macromolecular assemblies.

Over the last several years, the field of cryo-EM has undergone a revolution. Where once structural analysis by cryo-EM meant that low resolution maps were fit with high-resolution structures derived from other structural biology modalities such as X-ray crystallography or nuclear magnetic resonance spectroscopy, now, the data generated by cryo-EM can be of high enough resolution to directly generate atomic models for proteins and other biological macromolecules.

Time Lapse Video of Titan Krios Build

This video shows the progress of the build of the Titan Krios Microscope at the National CryoEM Facility at NCI- Frederick National Laboratory.

This revolution has been driven by several factors, including advances in microscope and camera technology, as well as improved computational methods for analyzing single particle cryo-EM data. Access to the latest microscope and detector technologies, which can be prohibitively expensive for many institutions is critical for acquiring the best quality data, and generating the highest resolution structures by this method. The NCI has created a user facility,  the National CryoEM Facility (NCEF) to meet the needs of cancer researchers in academic labs by providing access to state-of-the-art instrumentation for electron microscopy. The facility currently houses two Titan Krios microscopes equipped Falcon 3EC direct detectors and K3 Bioquantum detectors.  Both instruments have fringe free alignments which makes for more efficient use of grid area by allowing more images to be captured from a single hole.

In addition, NCI also supports efforts to test new platforms and new workflows to accelerate the development of next-generation tools for cryo-EM and its application to important problems of relevance to cancer biology.