Amyloid fibrils are insoluble, fibrous protein aggregates that accumulate in the tissues in a number of devastating diseases, including Alzheimer's disease, Diabetes type 2 and the Spongiform encephalopathies (eg. BSE, CJD). We have working towards the elucidation of the structure of these fibrillar aggregates using X-ray fibre diffraction and electron microscopy. We have shown that, although amyloid fibrils may be composed of different proteins associated with different diseases, they share common structural features. In particular, we have shown that amyloid fibrils are rich in beta-sheet conformation, irrespective of the conformation of the native precursor protein, and have a cross-beta core structure. Recently, it has become clear that smaller assemblies of amyloidogenic proteins may play a very important role in pathology of the diseases. This has led to our examing amyloid intermediates both structurally and for their cellular effect.


Research funding is awarded from Wellcome trust, BBSRC and Alzheimer's research UK and currently from MRC.