Life of the IBPC

The 2019 Edmond de Rothschild chair conference will be given by Dr Rik van Veen, tuesday 25th june 2019 at 11h ( Edmond de Rothschild Library- IBPC).
 «  On the trail of understanding antibiotic resistance - molecular mechanisms of multidrug transporters » (abstract)

 This lecture will be followed by a cocktail in the hall of the IBPC

Hendrik W. van Veen earned his B.Sc. and M.Sc. degrees in Biochemistry and PhD degree in Microbiology cum laude at the University of Wageningen. After post-doctoral work at the Universities of Groningen and Oxford, he obtained a research fellowship from the Royal Netherlands Academy of Arts and Sciences. He is currently Reader in Molecular Pharmacology at Cambridge University, and a teaching fellow at Clare College. His research group aims at the molecular mechanisms of multidrug transporters. He biochemically and functionally characterized the first-known bacterial homologue of the human multidrug resistance P-glycoprotein and expressed this ABC transporter (LmrA) in mammalian cells for a direct comparison of its pharmacological properties with those of P-glycoprotein. Established a role for ion-coupling in the energetics of LmrA in transport studies using membrane vesicles and proteoliposomes and in electrophysiological studies using giant unilamellar vesicles (port-a-patch) and planar bilayers (tip-dip technique). Demonstrated for the first time that catalytic reactions in LmrA can mediate ATP synthesis in the presence of reverse substrate gradients. Determined drug-protein stoichiometries using equilibrium drug binding and transport assays. Established the transport of small molecule drugs by the lipid-A ABC transporter MsbA and a role for proton coupling in the activity of this transporter. Identified structural elements in the human breast cancer resistance protein (ABCG2) that are responsible for protein-drug interactions in the substrate binding pocket. Identified the presence of multiple drug interaction sites in a MFS multidrug transporter (LmrP) and demonstrated variable (substrate-dependent) proton coupling. Discovered that ion coupling in certain bacterial MATE transporters is based on the simultaneous input of the proton-motive force and sodium-motive force. Generated mechanistic interpretations of crystal structures and cryo-EM structures of multidrug transporters in ABC and RND families.