Two large grants from the Dutch funding agency NWO Chemical Sciences have been awarded to teams of biochemistry researchers at Utrecht University. They will each receive two million euros to start new, challenging and innovative research lines. In total, NWO awarded four out of thirteen received research proposals. The research teams that will receive the grant are Marc Baldus and Alexandre Bonvin & Albert Heck and Geert-Jan Boons.
Almost all cell surface and secreted proteins are modified by covalently-linked carbohydrate moieties and the glycan structures on these so-called glycoproteins are essential mediators for biological processes such as protein folding, cell signaling, fertilization, embryogenesis, neuronal development, hormone activity and the proliferation of cells and their organization into specific tissues. In addition, overwhelming data supports the relevance of glycosylation in pathogen recognition, inflammation, innate immune responses, and the development of autoimmune diseases and cancer. Advances in understanding the biological roles played by glycans on proteins, along with the factors that influence or alter their functions, will be central to understanding biology and will provide important avenues for the development of therapeutics, diagnostics and nutraceuticals of the future. We propose to develop an integrated approach of sophisticated synthetic chemistry, mass spectrometry and biology to uncover structures and functions of cell surface glycoconjugates.
Physiological processes can only rarely be attributed to individual molecules but rather involve complex interactions within molecular assemblies on different temporal and spatial scales. In the latter case, compartmentalization via membranes is a common principle in nature to control fundamental biological functions, including bioenergetics, communication, sensing, and organization. In these processes, membrane-embedded proteins (MPs) play a central role and great progress has been made in elucidating their three-dimensional atomic structures. To describe and understand these processes in situ and at the most detailed, i.e., atomic level, we propose an integrative approach that combines latest advancements in the fields of experimental cellular structural biology (in particular NMR) and computational structural biology to explicitly study membrane complexes and their workings at atomic scale.