Prion growth and toxicity
This work aims to characterise the ways that prions propagate (how prions grow or replicate) and understand its relationship to prion strains, barriers to spread prions between animals, the onset of neurological disease and clinically silent (healthy) carrier states. In particular, extensive efforts are underway to attempt production of high-concentrations prions and the toxic species from manufactured prion protein for subsequent structural analysis in the MRC Prion Unit. The unique biology of prions, allied with the risks to public health posed by prion zoonoses such as BSE, has focused much attention on understanding the molecular basis of prion propagation and pathogenesis (how they damage nerve cells). However, it is clear that the underlying molecular mechanisms, involving deposits of an abnormally shaped protein, are of much wider significance. Recent advances at the Unit and elsewhere suggest that prions themselves are not directly toxic, but rather their spread involves production of another molecule. We have proposed an explanation of these phenomena, centering on the kinetics of prion propagation, and we are testing this model using various experimental systems.