Research

Cryo-EM

Cryo-Transmission Electron Microscopy (cryo-EM) studies the structure of frozen hydrated biological samples by transmission electron microscopy. Generally, several images of the frozen samples are recorded, sometimes at different sample tilt angles, and are computationally combined into one merged data set that can show the high-resolution structure of the sample in three dimensions.

Cryo-EM can be divided into three domains: Electron tomography, single-particle cryo-EM, and electron crystallography. The first studies cellular environments and usually is limited to a resolution of a few nanometers. The second studies individual larger proteins or protein complexes, and is now reaching 4Å resolution in favorable cases (GroEL, large viruses). The third, electron crystallography, studies the structure of membrane proteins that have been reconstituted into lipid membranes and two-dimensionally crystallized. Electron crystallography has been used to determine the structure of 8 membrane proteins at atomic resolution (< 4Å) so far, and has produced 3D membrane protein maps that reached 1.9Å resolution (See the list of available structures from electron crystallography). Our laboratory is employing all three methods. We also develop methods with the aim of being able to rapidly determine the 3D structure of membrane proteins, using primarily electrons as probes.