We study the atomic structure, mechanism and cellular function of membrane transport proteins with main focus on neuroscience, how membrane transport proteins orchestrate neuronal signaling networks in the brain, and how these are affected in neurological and psychiatric disorders. We use electron microscopy and X-ray diffraction as our key methodologies.
40-80% of energy consumed in the brain is used by P-type ATPase ion pumps that maintain electrochemical gradients for, e.g. Na+, K+ and Ca2+. These gradients energize numerous other processes in cell membranes such as neurotransmitter transporters, ion channel receptors, and Ca2+ signaling. Similarly, P4-ATPase lipid flippases maintain the asymmetric distributions of lipids in the biological membranes as required for, e.g. vesicle-mediated signal transmission, cellular trafficking, and lipid-based signaling.
We study the structure and function of these membrane transporters and how they relate to brain function and diseases with the long-term goal of understanding higher-order molecular networks in brain cell membranes. We use primarily membrane protein crystallography, biochemical assays, electrophysiology, and fluorescence spectroscopy, and are implementing cryo-EM and EM tomography and establishing XFEL and neutron scattering studies on biomembrane samples.
Our research provides a “first view” of new opportunities in drug discovery and biotechnology, so we are also pursuing spin-out and start-up activities, as well as industry collaborations.