Mechanisms of transmembrane ion and lipid transport
We are interested in the mechanisms by which ion and lipid transporters and channels catalyze selective transport processes across the cell membrane. Towards this end, we use interdisciplinary approaches to study the structure and function of diverse families of ion transport proteins that are central to human physiology. As a prerequisite for functional studies, we determine structures of these transmembrane transport proteins using single particle cryo-electron microscopy and X-ray crystallography. Guided by these structures, we subsequently investigate transport mechanisms by means of biochemical, structural and electrophysiological methods.
Over the years, we have characterized different protein families including the ClC family of chloride channels and transporters and Pentameric Ligand-gated Ion Channels (pLGICs). Current research focuses on members of the TMEM16 family of Ca2+-activated chloride channels and lipid scramblases, the LRRC8 family of volume-regulated anion channels, the SLC26 family of multifunctional anion transporters and the SLC11/NRAMP family of proton-coupled transition metal ion transporters.
In the course of our studies, we have determined the first structures of family members under investigation, characterized their functional properties and studied the interactions with small and macromolecular ligands. In our work we aim to make fundamental contributions to the understanding of transport processes of medical relevance and their regulation by pharmacological compounds. In that way we hope to contribute to the development of novel therapeutic strategies by targeting ion and lipid transport proteins.