Proton transport and proton-coupled transport (EU Research Framework Programme H2020 / Marie Skłodowska-Curie Actions)

Abstract

Secure, competitive, and sustainable energy production is a major challenge facing human societies. Biomimetic solutionssuch as the development of new biofuel cells are hampered by our thus far incomplete understanding of proton transferreactions. The same holds for health threats to humanity: Curing diseases like cancer, obesity, chronic gastritis, gastric andduodenal ulcers, requires to pharmacologically interfere - in their molecular details - with yet unresolved proton transferreactions.Here we aim at clarifying the molecular reaction mechanism in the confines of interfacial water layers and proteinaceouscavities with emphasis on arrangement and mobility of proton relay moieties. Achieving this requires an interdisciplinary,multi-level approach comprising cutting edge technologies like second harmonic imaging, single molecule and time resolvedfluorescence microscopy and spectroscopy, advanced calculations of proton transfer, bioengineering of membrane channeland transporter containing systems, synthetic design of biomimetic proton channels, solving protein structures and rational drug design.PROTON will train 15 PhD students, who will acquire a solid state-of-the-art multidisciplinary scientific training in all kinds ofproton migration/reaction systems, covering from basic science to industrial applications, thus preparing them to generatenew scientific knowledge of the highest impact. In addition, practical training on transferable skills will increase theiremployability and qualify them for responsible positions in private and public sectors. Cross-disciplinary strategies and closecollaboration with industry will enable them to resolve the molecular details of proton driven processes in all kinds of settings- enabling the improvement of biomimetic applications – up to fuel cells - and to identify lead substances which may serve topharmacologically interfere with proton transport through membrane channels and transporters.

Publications as an introduction to the project

  1. Rupprecht et al. (2010) Role of the transmembrane potential in the membrane proton leak. Biophys. J. 98, 1503-1511
  2. Jovanovic, O., Pashkovskaya, A.A., Annibal, A., Vazdar, M., Burchardt, N., Sansone, A., Gille, L., Fedorova, M., Ferreri, C., Pohl, E.E.(2015) The molecular mechanism behind reactive aldehyde action on transmembrane translocations of proton and potassium ions. Free Radical Biology and Medicine
  3. Macher, G., Koehler, M., Rupprecht, A., Kreiter, J., Hinterdorfer, P., Pohl, E.E. (2018) Inhibition of mitochondrial UCP1 and UCP3 by purine nucleotides and phosphate. Biochim Biophys Acta 1860, 664–672
  4. Pohl, EE., Rupprecht, A., Macher, G., Hilse, KE (2019) Important Trends in UCP3 Investigation. Front Physiol. 2019; 10:470

Publications as Results from the project

under construction

Link JKU 1

Link VetDoc 2