The interests of the van der Wel research group are in the application of solid state NMR to biological structure determination. Biological ssNMR allows measurements of structural and motional features of (partially) immobilized biomolecules, and is of particular interest due to its ability to access such information in a site-specific manner without requiring solublity or crystallinity.

Various human disorders involve the misfolding of proteins into fibrillar aggregates (including diseases like Huntington and Alzheimer’s Disorders), and one of the group’s research aims is to address the structure and formation of the misfolded proteins within amyloid-like fibrillar aggregates. A particular focus is on the misfolding of expanded polyglutamine proteins, including that of huntingtin, which is mutated in Huntington’s Disease. Furthermore, in the cells many proteins are interact with the lipid bilayers that make up biological membranes.  This association is often critical for their functional  roles, and can induce structural or functional changes.  The interests of the van der Wel research group are in the interplay between the lipids in the membrane and the membrane-bound proteins, and how this interaction affects protein structure and function.  Importantly, this is a two-way process, with protein-induced effects on the membrane leading in some cases to fatal disruptions of the membrane’s bilayer structure.

Solid-state NMR provides unique capabilities to investigate these important biophysical and structural questions. The links to the left address some of these topics, including the use of different experimental SSNMR approaches, structural measurements on misfolded protein aggregates, and atomic-level studies of protein-lipid interactions.

Source:  http://www.structbio.pitt.edu/webusers/pvdwel/