Understanding Movement and Mechanism in essential Mammalian Membrane Transporters

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We study the architecture and functional dynamics of membrane proteins, many medically relevant. Special interest is on large multi-subunit complexes including supercomplexes as well as on transporter systems and their interaction with intra-cellular signalling pathways. There is increasing evidence that membrane proteins do not act alone, but that they are organised as nano-machineries which function through the concerted action of its individual components with high precision and specificity observed in both time and space. We are seeking to unravel the principles underlying the architecture and dynamics of these protein nano-machineries as well as their function and regulation. Our experimental approach focuses on the use of magnetic resonance spectroscopy specifically electron paramagnetic resonance (EPR) and Nuclear Magnetic Resonance (NMR) techniques in combination with molecular biological, and biochemical approaches. In addition advanced molecular dynamics techniques (MD) are used to underpin the experimental observations to provide a dynamic description of function. This project addesses this important theme of transport across biological membrane through the study of a specific bacterial aspartate transporter which is an archaeal homolog of mammalian glutamate transporters, implicated in various neurological diseases including epilepsy and Alzheimer's disease. Recent static crystal structures have suggested large scale conformational changes and we aim to probe the functional dynamics of the protein function using a combination of state-of-the-art magnetic resonance techniques and molecular dynamics simulations.