The ability of prions to convert normal prion protein into additional prions can be exploited for the purpose of diagnosing and studying prion diseases. Prions can be detected by infecting susceptible cells or by using a technique called RT-QuIC. In both experimental systems, it is important that a compatible version of the normal prion protein is used for detecting prions. One such version is the prion protein from the bank vole. Bank voles are rodents that are remarkably susceptible to prions, and the bank vole prion protein can easily be converted into prions by prion aggregates from several different animal species. The goal of this proposal is to further optimize the normal bank vole prion protein so that it becomes even more susceptible to prions, enhancing the ability of prions to be studied using cells and improving the diagnostic sensitivity of the RT-QuIC test.