Abstract
(Englisch)
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Water is essential to life. 70% of the water in cells belongs to the hydration shells of proteins, lipid membranes or occupies protein cavities - so-called interfacial water. The difference in structure between interfacial water and bulk water gives rise to a key force in molecular biology: hydrophobic attraction. We do not fully understand how exactly this force contributes to protein folding, stability, structure, function, dynamics or membrane fusion. WATER aims to train 16 PhD students to unravel the multiple roles of interfacial water in biological membranes. They will characterise water mobility and ordering inside membrane receptors, carrier proteins and channels, adjacent to their ligands and lipid bilayers, and in the reaction centres of membrane-bound enzymes, using a broad methodological spectrum including cryo-electron microscopy, simulations, light-spectroscopy and imaging. To assess the functional consequences of water confinement, they will analyze facilitated water and solute transport, chemical reactions inside proteins, ligand-protein interactions, the intraprotein H-bond network, and membrane fusion events, exploiting, e.g., electrophysiology and synthetic chemistry. The results will pave the way for the development of personalised, targeted therapies and more effective drugs and vaccines through improved binding and delivery. Biotechnological applications include artificial channels in biomimetic applications. WATER will bring together world-class theoreticians, experimentalists and computational scientists to provide multidisciplinary training in biophysics, molecular biology, medicinal and organic chemistry, structural and synthetic biology, advanced microscopy and computer science. Besides scientific excellence, WATER offers a cross-sectoral approach, involving industry from start-ups to large pharmaceutical companies, and soft skills training enhancing DC’s abilities to translate scientific discoveries and improve their employability.
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