Home : People : Faculty : Patrick van der Wel

Patrick van der Wel

Address:
Department of Structural Biology
University of Pittsburgh
BST3; room 2044
3501 Fifth Ave
Pittsburgh, PA 15260

Phone: (412) 383-9896
Fax: (412) 648-9008
Email: pvdwel@pitt.edu
Homepage: Visit

PhD.: 2002, University of Arkansas
Postdoc: Massachusetts Institute of Technology

Research:
Our primary interest is in the application and development of solid state NMR methods to the study of proteins that are aggregated or otherwise immobilized. This 'immobilized' state can take a variety of forms, but notably includes amyloid-like fibrils and membrane-bound proteins, sample conditions that are inherently difficult to study by methods like X-ray crystallography and solution NMR. Multiple human disorders (e.g. Alzheimer's disease) are characterized by the misfolding and aggregation of normally un-aggregated proteins into fibrillar structures (amyloid fibrils). Understanding the formation and structure of these fibrils has been an experimental challenge, with ssNMR uniquely able to provide site-resolved measurements of the structure and dynamics of the fibrillar state. We are employing ssNMR methods to study such amyloid fibrils and thereby further our understanding of the underlying mechanisms of their formation. Membrane-bound proteins mediate the cross-membrane transport of chemicals (e.g. ions) and information, but also affect their membrane environment. One of the issues in studying membrane proteins is that their activity (and structure) is often sensitive to the nature of this surrounding membrane (or the lack thereof), which can complicate the execution and interpretation of structure determinations based on solution NMR and X-ray crystallography. Our interest is in the study of membrane proteins while bound to lipid bilayers, and study the protein-lipid interaction under these conditions. Various membrane-associated proteins are even able to modulate the structure of the surrounding membrane, an ability that is essential for the cell and necessary processes such as membrane fusion and fission.