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 in Lausanne at the University of Lausanne and the EPFL 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 50nm to 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 has not formed ice crystals. These samples are then imaged in a high-end cryo-EM instrument.
The Stahlberg group operates own electron microscopes for the purpose of advancing the method of cryo-EM. These include a 300kV Titan Krios prototype and a 200kV Talos. Stahlberg also directs the Dubochet Center for Imaging (DCI) in Lausanne, which is a common initiative of the EPFL, the University of Lausanne and the University of Geneva. The DCI operates several high-end cryo-EM instruments, including two Titan Krios with frontier features, such as cold-FEG electron sources and latest energy filtration and detector configuration. 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.
Stahlberg has a dual professorship affiliation as full professor at EPFL and at University of Lausanne.
Function in NCCR
- Principal Investigator (PI)
Dual professorship at the EPFL and the University of Lausanne, Director of the Dubochet Center for Imaging of the EPFL, University of Lausanne and the University of Geneva.
Professor at the Biozentrum of the University of Basel, Director of the Center for Cellular Imaging and Nano Analytics (C-CINA) of the 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
- 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)