Cryo-electron microscopy (cryo-EM) is a method that uses rapidly frozen thin layers of suspensions of a protein solution, and images this an electron microscope at liquid-nitrogen temperature. The Stahlberg group at the University of Basel uses cryo-EM to study the structure of membrane proteins. This is typically done by detergent-solubilization of overexpressed membrane proteins, biochemical purification of the membrane proteins in detergent, followed by forming a 100nm thin layer of the protein suspension over a fenestrated carbon film, which is quick-frozen to liquid nitrogen temperature. This results in a thin, free-standing film of vitrified membrane protein solution, in which the protein is frozen but the water had not formed ice crystals. These samples are then imaged in a high-end cryo-EM instrument.
Stahlberg directs the Center for Cellular Imaging and Nano Analytics (C-CINA) at the University Basel, Switzerland, which operates several high-end cryo-EM instruments. These instruments are used to automatically record image data in form of dose-fractionated image frames (i.e., movies), of the frozen membrane protein particles.
Frames in movies are motion-corrected to compensate electron-beam induced sample movement. Particle images are extracted from the large movies, and submitted to computational image processing, resulting in the high-resolution 3D structure of the membrane proteins.
The C-CINA is also developing methods to reduce the amount of required sample, automate and accelerate the data collection in the cryo-EM instruments, and improve the final resolution.
Function in NCCR
- Principal Investigator (PI)
Professor at the Center for Cellular Imaging and Nano Analytics (C-CINA), Biozentrum, University of Basel
- PD (Habilitation) in Biophysics at the University of Basel
- Ph.D. in Structural Biology at the Ecole Polytechnique Fédérale, Lausanne
- M.Sc. in Physics at the Technical University of Berlin
- American Chemical Society
- Microscopy Society of America (MSA)
- Swiss Society for Optics and Microscopy (SSOM)
- German Physical Society (1989-1994)
- W.M.Keck Award (2009)
- UC Davis Chancellor’s Fellow Award (2008-2012)
- NSF CAREER award (2005)