Research SummaryStructural investigations into the mechanism and pharmacology of ion-coupled membrane transporters
All cellular life is bound by one or more membrane bilayers made of lipid molecules that compartmentalize intracellular from the extracellular constituents. However, cells have to constantly interact and exchange material with the environment in order to obtain nutrition, remove metabolic end products, and respond to external cues. Specialized protein machinery in the form of transporters allow selective influx or efflux of metabolites important for cellular physiology or to remove toxic end products, respectively. A subset of integral membrane transporters drive uphill substrate uptake by coupling it with ionic electrochemical gradients. This phenomenon encompasses both symport (moving substrates and ions together) and antiport (substrate moving against ionic flow) and is crucial for the physiological processes as diverse as neurotransmitter transport, sugar intake and antibiotic efflux.
Research in my lab is aimed at obtaining a holistic understanding of the transport machinery involved in neurotransmitter uptake with a specific emphasis on obtaining high-resolution structural information on transporters involved in this physiological niche. Understanding mechanisms of neurotransmitter transport through structural studies will allow us to obtain atomic level insights into how this molecular machinery works and how certain small molecule inhibitors block transport and alleviate conditions including depression, psychosis and hyperkinetic disorders.
Figure Legend: Mechanisms of substrate transport employed by membrane (horizontal gray bar) transporters. Direction and concentration of substrate flow (brick red) and ion flow (blue) are represented as shaded arrows.