Molecular and phenotypic analysis of prion strains

Prions are infectious agents causing a group of closely related lethal brain diseases that include scrapie in sheep, BSE in cattle, CWD in deer and elk and various forms of CJD in humans. Unlike other infectious agents (bacteria and viruses) the infectious particle does not contain genetic information (genes) but instead consists of pathogenic assemblies of prion protein (PrP) which replicate in the central nervous system leading to progressive loss of brain function and eventually death of the infected host. Although prions do not carry genetic material they come in several different forms, called prion strains which are responsible for different forms of the disease in humans and animals. Our research aims to define the fundamental biology of what makes prion strains different from one another why some are able to cross from animals to humans to cause disease. Recently we revealed prion structures at near-atomic scale resolution and showed that infectious prion fibrils from different mouse prion strains are built from distinctly folded chains of PrP. Methods we have established can now be applied to explore structural similarities between different human and animal prion strains. Overall we aim to establish a comprehensive structure-based classification system and use this to evaluate which existing or newly emerging animal prion strains might pose a threat to humans. This information will have direct translation to protecting public health.