I have continued to contribute to research into prion disease and I now lead my own programme of research into novel diagnostic methods for use in prion disease and other protein conformational disorders. We are interested in defining the mechanism of prion replication at the atomic level which includes determining the structures of synthetic prions by cryo-electron microscopy and identifying the essential components contained within a brain homogenate that are required for prion replication in vitro. The crucial requirement for brain homogenate as a supplement to replicate prions rather than amyloid is being investigated, both by fractionation and modification of the brain homogenate substrate and by mass spectrometric analysis of the purified synthetic prions to determine what components additional to PrP are required to generate a prion.