Research

Our goal is to enhance understanding of protein physiology in an integrative way by exploring connections between different cellular pathways. As scientists, we continually adjust our experimental approaches to new questions. This is enabled by establishing a broad conceptual foundation. Rather than asking if a project is feasible, we ask what is necessary to make it possible.

structural biology

Seeing is believing (and understanding). Structural Biology of bio-macromolecules is the most direct way to gain insights into their workings. With our focus on proteins and protein-protein complexes, cryogenic electron microscopy (cryo-EM) has become an extremely powerful tool. By imaging and reconstructing three-dimensional structures in native-like environments, we are able to make unprecedented structure-function correlations. We use single particle analysis of proteins solubilized in detergent or reconstituted into nanodiscs or liposomes to understand changes in protein conformation and dynamics upon protein-protein complex formation.

protein function

To understand how proteins work and contribute to (patho)physiology, it is essential to study their function under controlled conditions. This means reconstituting individual proteins or multi-molecular systems from purified components for activity assays. Fluorescence spectroscopy combined with rapid mixing techniques offers a remarkably sensitive readout for assaying enzyme function as well as macroscopic ion channel activity. To obtain detailed information about ion channel function, single-channel electrophysiology in planar lipid bilayers provides accurate insights into opening and closing kinetics under defined conditions.

protein folding

Textbooks teach us about four levels of protein structure: primary, secondary, tertiary, and quaternary structure. In cells, the goal is to reach a thermodynamically stable, functional, three-dimensional structure. Folding studies in the test tube on the other hand provide insights into protein stability and dynamics. Kinetic folding studies are especially informative, showing, in many cases, the behavior of different protein conformations.