Fellow

Protein misfolding is a crucial factor in the development and progression of a number of human diseases, ranging from cystic fibrosis to systemic amyloidosis, and possibly including type II diabetes and Alzheimer’s disease. Chris Dobson is Professor of Chemical and Structural Biology in the Department of Chemistry in Oxford. He is one of the world’s leading contributors to our current understanding of how proteins fold correctly to generate normal biological function yet misfold to generate disease. He has developed and applied a wide range of biophysical and biochemical techniques for this purpose, and his use of these techniques, in conjunction with novel theoretical and conceptual approaches, is unravelling the molecular basis of these highly complex processes. He has studied in particular the mechanism through which mutational variants of the protein lysozyme are able to form amyloid fibrils in vitro and hence has established in molecular detail the structural transitions that underlie this particular process of amyloid fibrillogenesis. Subsequently the results of his many investigations of the normal and aberrant folding of a variety of proteins, has led him to put forward the idea that the ability to form the amyloid fibril structure is a generic property of peptides and proteins. On this hypothesis the formation of amyloid fibrils in vivo results from the failure of the regulatory mechanisms that normally prevent protein misfolding and aggregation. This idea provides both a unified conceptual basis for amyloid fibrillogenesis and a rational basis on which to develop new therapeutic approaches. In summary, Chris Dobson has pioneered the application of advanced biophysical and biochemical techniques to understand the molecular basis of normal and abnormal mechanisms of protein folding, processes that are fundamental to both health and disease.