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. We specialize in state-of-the-art solid-state NMR (ssNMR) spectroscopy, which we use to probe the structure and dynamics of nano-sized assemblies. One biophysical 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 other non-biological assemblies. Our research is made possible by funding from the CHDI Foundation, Campagneteam Huntington and the NIH, along with institutional support from the University of Groningen.
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.
Protein misfolding & Huntington’s disease.
We use also 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. For example, funded by the US NIH, we have been studying the misfolding of expanded polyglutamine proteins that are mutated in Huntington’s disease (HD), ataxias and other diseases. Through our mechanistic and structural studies we further our understanding of the disease-causing processes to inform the design of new treatment strategies.
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.
Physics of Cancer
We are part of the interdisciplinary Physics of Cancer (PhyCan) network at the Zernike Institute and affiliated institutes at the University of Groningen. We are using solid-state NMR among various other methods to provide a molecular perspective on the structural and dynamical underpinnings of the unique physical properties of cancer cells and cancer tissues. For more information visit the PhyCan website.
Advanced solid-state NMR spectroscopy.
We also develop new methods in ssNMR 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 with in silico work, towards techniques to measure structural as well as dynamic properties.
Questions? Interested in joining the lab, reprints or a collaboration? Contact us!
Selected Publications
(see here for a complete listing)
- Fibril polymorphism affects immobilized non-amyloid flanking domains of huntingtin exon1 rather than its polyglutamine core. Lin, H.K., Boatz, J.C., Krabbendam, I.E., Kodali, R., Hou, Z., Wetzel, R., Dolga, A.M., Poirier, M.A., and Van der Wel, P.C.A. (2017) Nature Commum. [URL]
- Cataract-associated P23T γD-crystallin retains a native-like fold in amorphous-looking aggregates formed at physiological pH. Boatz, J.C., Whitley, M.J., Li, M., Gronenborn, A.M., & Van der Wel, P.C.A. (2017) Nature Commun. 8:15137 (DOI)
- Huntingtin exon 1 fibrils feature an interdigitated β-hairpin-based polyglutamine core. Hoop, C.L., Lin, H.-K., Kar, K., Magyarfalvi, G., Lamley, J., Boatz, J.C., Mandal, A., Lewandowski, J., Wetzel, R., Van der Wel, P.C.A. (2016) Proc. Natl. Acad. Sci. USA. 113(6): 1546-51 (At journal)
- Structural changes and pro-apoptotic peroxidase activity of cardiolipin-bound mitochondrial cytochrome c. Mandal, A., Hoop, C.L., DeLucia, M., Kodali, R., Kagan, V., Ahn, J., Van der Wel, P.C.A.* (2015) Biophys. J. 109(9): 1873–1884 (At journal)
- Lipid Dynamics and Protein-Lipid Interactions in Integral Membrane Proteins: Insights from Solid-State NMR. Van der Wel, P.C.A.* (2014) eMagRes. 3: 111–118 (DOI) (PDF download)
- Amyloid-like fibrils from a domain-swapping protein feature a parallel, in-register conformation without native-like interactions. Li, J.; Hoop, C.L.; Kodali, R.; Sivanandam, V.N.,; and Van der Wel, P.C.A.* (2011) J. Biol. Chem. 286(33): 28988-95 [at journal][PubMed]
- The Aggregation-Enhancing Huntingtin N-terminus is Helical in Amyloid Fibrils. Sivanandam, V.N., Jayaraman, M., Hoop, C.L., Kodali, R., Wetzel, R., and Van der Wel, P.C.A. (2011) J. Am. Chem. Soc. 133(12): 4558–4566 [at journal]