MEMBRANE BIOCHEMISTRY OF SOLUTE TRANSPORT
Biological membranes efficiently divide space into two compartments. The proteins residing in these membranes control the exchange of information and solutes, such as ions and carbohydrates, and thereby directly affect the internal milieu of cells and organelles. We study solute carriers, one of the most occurring transporter types in all kingdoms of life, but also one that is relatively understudied. We are interested in their molecular design, their role in cellular physiology, and contribution to transepithelial solute transport.
Membrane transport proteins are small miracles. They operate in a complex chemico-physical environment as they are simultaneously exposed to hydrophobic and hydrophilic compartments, to membrane regions of high pressure and high tension, and to a strong electrical field across the membrane. We first aim to answer the question how the ability to transport is coded into these proteins by combining structural and functional studies on solute carriers. We want to obtain a mechanistic understanding of transport, and its regulation by other proteins, protein domains, and the lipid bilayer. By studying different, but structurally related families of transporters we will highlight how general certain design principles are, but also reveal plasticity towards adopting different regulatory domains. Subsequently, we will use these mechanistic insights to modulate the activities of solute carriers in living cells and tissues to determine how transport systems in opposing membranes contribute to transepithelial solute transport.
Scientific progress is intimately tied to methodological progress, which is particularly true for membrane proteins. To support our aims, we therefor develop novel enabling technologies for protein research in parallel. Examples of our methodological contributions can be found in the field of membrane reconstitution of transport proteins, high-throughput screening pipelines based on FX cloning and GFP for optimizing protein overexpression, and the generation of (synthetic) nanobodies, camelid single-domain antibodies, for conformational arrest of proteins.