Welcome to the website of the solid-state NMR research group supervised by Patrick van der Wel, since Aug. 2018 at the Zernike Institute for Advanced Materials of the University of Groningen. Our group is one of the chemistry-oriented research groups of the Zernike Institute, with research interests cross the boundaries of physical chemistry, biochemistry/biophysics, analytical chemistry, and materials science. We specialize in state-of-the-art solid-state NMR (ssNMR) spectroscopy, which is a we use to probe the chemical composition, structure and dynamics of nano-sized assemblies. One focus of our research is studying the molecular causes of neurodegenerative diseases, and the role of protein misfolding, protein deposition, and mitochondrial protein-lipid interactions therein (see below). At the same time we also use similar methods to understand the structure-function relationships behind materials and different types of non-biological assemblies. Our research is made possible by funding from the NWO, CHDI Foundation, Campagneteam Huntington, EHDN, and the NIH, along with support from the University of Groningen.
Protein misfolding & Huntington’s disease.
We use ssNMR spectroscopy to structurally study the misfolding and self-assembly of proteins – the hallmarks of many neurodegenerative diseases. Integrating NMR with other biophysical techniques, we determine the structure of protein deposits and the mechanism of aggregate formation. In particular, we have been studying the misfolding of expanded polyglutamine proteins that are mutated in Huntington’s disease (HD), ataxias and other diseases. By combining NMR measurements with biochemical and mechanistic studies, we further our understanding of the disease-causing processes to inform the design of new treatment strategies.
Self-assembling nanomaterials.
Self-assembly of smaller compounds and (macro)molecules into supramolecular assemblies allows for the production of nano-materials with various properties. We use ssNMR to probe the structure of such nano-structures and thus help understand possible structure-based design principles. In some cases we also deploy principles from biology, leading to bio-mimetic materials. A special focus in this area is on soft and responsive materials including polysaccharide-based hydrogels. These have important roles in biological (extracellular matrices), pharmaceutical and biomedical engineering contexts.
Mitochondrial protein-lipid interactions in apoptosis.
We also study the interplay between lipid membranes and membrane-binding proteins. This is often a two-way process, where proteins modulate membrane structure and membranes modulate protein structure and function. In one NIH-funded research project, we have for example been investigating protein-lipid interactions that are critical in the early stages of mitochondrial apoptosis. Part of our interest in this process stems from the fact that it is plays a critical role in the neurodegeneration in HD and related diseases. Thus, we aim to obtain new mechanistic insights that may pave the way for possible new treatment strategies.
Advanced solid-state NMR spectroscopy: methods and instrumentation.
To enable the above application studies, we develop new methods and approaches in NMR and especially solid-state NMR. We have in-house dedicated ssNMR instrumentation (Bruker NEO 600MHz with MAS probes), which will soon be expanded via funding from the Dutch NWO. The latter will enable a specialized new DNP/ssNMR facility at the University of Groningen. In addition, we are associated with the national uNMR-NL network that offers access to additional advanced instrumentation, including MAS NMR at 1.2 GHz and high-field DNP/ssNMR.
We try to enable new experiments and new insights, mostly driven by the specific needs of our own (and collaborative) projects. To do so we combine experimental spectroscopy with in silico work, towards techniques to measure structural as well as dynamic properties. A current research interest is to develop and enable in-situ irradiation during MAS NMR, as tool for understanding a wide range of topics, from light-sensitive materials, to photochemical studies and optogenetic applications. See also our recent paper on this topic.
Questions? Interested in joining the lab, reprints or a collaboration? Contact us!