Research
Membrane asymmetry and lipid trafficking
We are interested in membrane proteins that impact the organization of the lipid bilayer: Factors that build up membrane lipid asymmetry and lipid scramblases that randomize the distribution of lipids between the leaflets. We investigate how certain lipid species reach their destination in a distinct leaflet of the bilayer, why lipid asymmetry is important in membranes and which functions are elicited through the concerted breakdown of this asymmetry by scramblases. To address such questions, we structurally describe lipid transporters to reveal their ‘inner workings’ and regulation. The subcellular localization of these transporters to understand the cellular function as well as the network of interacting proteins is another emphasis.
Ion channels
We investigate ion channels, particularly of intracellular membranes like the lysosome. The lysosome is the cellular recycling machinery and is increasingly recognized as sensor for the metabolic state of the cell. Lysosomes are pivotal for the removal of protein aggregates from the cytosol and this connects them to neurological diseases like Parkinson disease. Because ion gradients across the lysosomal membrane are crucial for the function of this organelle, ion channels are important regulators of lysosomal transport and fusion as well as the degradation of lysosomal contents. Modulation of ion channel activity in these organelles thus holds great prospects for medical applications. In our lab, we strive to understand how ion channels achieve selectivity and how they are gated to open or close. We further investigate the significance of ion gradients across the lysosomal membrane for the turnover of autophagosomes and maintenance of the luminal pH.
Method development for cryo-EM
Besides our research activities in fundamental science, we develop methods to accelerate and enhance structure determination of membrane proteins by cryo-EM. We have designed rigidified macrobodies that are built from nanobodies to improve particle alignment procedures for small membrane proteins to ultimately increase the resolution of target proteins. Macrobodies were first developed by us as crystallization chaperones but a new rigidified version with a universal linker (called Pro-Macrobodies) enables their use as highly efficient fiducial markers in vitrified samples for cryo-EM.