Understanding Macromolecular Structure and Dynamics with Cryo-EM

Our lab aims at a quantitative understanding of how biomolecular machines function in their native biological environment. Our approach is inspired by the idea that once we understand biology at the atomic level, then it becomes tractable by the laws and principles of chemistry and physics. Biological macromolecules adopt intricate three-dimensional arrangments that are critical to their function. By taking many hundreds of thousands of images of the molecules with our electron microscopes and combining all of the information from these images, we can visualize the three-dimensional structure of these molecules almost at atomic detail. Having a molecular picture of protein assemblies enables us to learn how they work, and provides the possibility to modify them in a way that may improve or revise their function for therapeutic treatment in disease. Since both the physical dimension and the operation level of the systems we study are at the nanoscale, we collectively describe this as biomolecular nanoscopy.

More specifically, we are interested in the molecular machinery that individual cells employ to defend themselves against infection. Our research interests include the structure and function of host factors in intracellular immunity, the mechanism of force generation by large macromolecular assemblies on membranes and the role of autophagy in pathogen elimination. We combine cryo-EM with other structural methods to visualize the macromolecular complexes involved in these processes, and apply quantitative biochemical and biophysical tools to dissect their mechanism of action. The challenges implicit to this endeavour also lead us to develop and apply new approaches for cryo-EM sample preparation, image processing and data interpretation. Please have a look at the individual research areas for more details.