Development of innovative prion disease models and study of the pathobiology of synthetic prions in transgenic mice and unusual hosts. and unusual hosts

1) To gain insight on the molecular elements required for a prion protein to be able to show a prion behaviour. This is, to define the basic components of a PrPC sequence that allow the spontaneous conversion to the pathogenic isoform. 2) To employ the knowledge derived from the first objective to the development of new animal models, one with enhanced susceptibility to provide a fast animal model of disease useful to evaluate new therapies rapidly; and another one, as a proof of concept of a potential therapy based on proteins with dominant-negative
capacity.