Cell Biology and function of the prion protein in health and disease

Creutzfeldt-Jakob disease in humans is a severe, rapidly progressive, ultimately fatal, degenerative brain disorder, caused by an infectious agent which is a misfolded version of a normal cellular protein, called the prion protein. The infectious agent replicates by converting the normal prion protein, to a misfolded disease state. Developing cells that can propagate bona-fide human prions has been an important goal of the prion field for decades. We have successfully engineered mouse cancer cells to be able to propagate human prions from a variety of strains including the causative agent of ‘mad cow’ disease. We aim to use these cells to develop highly sensitive and accurate automated cell-based bioassays, which can be used to measure infectious prions in a range of human tissues and bio-fluids from patients. This assay can be a “gold standard” for diagnosis of prions and validation of other diagnostic assays and provide a biomarker for studying response to treatment. It also has the potential to be scaled up to process large numbers of samples per year, as has already been done for the mouse prion bioassay.