Procedures for the in vitro generation of infectious prion, PrP^Sc, from non-infectious brain-derived PrP^C, were introduced in 2001. However, the underlying mechanisms and requirements for the efficient in vitro amplification have not been investigated in depth. Thus a robust, universal procedure that can reliably amplify prions from all prion strains from all species is still missing.

In this project, natural rodent prions (mouse and hamster) will be used as seeds to convert brain derived PrP^C. The method is based on a technique termed “Protein Cyclic Misfolding Amplification (PMCA). PrP^Sc will be generated in this way, and detected by western blotting. It is the aim to systematically screen additives for their capacity to enhance the efficiency of conversion. Initial test have suggested that a substantial improvement of the reaction can be expected. The knowledge of optimal amplification conditions will be of fundamental importance for the systematic investigation of the PrP^C to PrP^Sc conversion mechanism.

The successfull candidate will be introduced into all nescessary molecular biological and protein biochemical techniques. The obtained products will be first characterized by western blotting quantification, and at a later stage also by biophysical techniques including CD-spectroscopy, fourier transformed infrared spectroscopy. The project will be carried out in close association with other ongoing projects in the laboratory.