A select group of prion researchers from around the world gathered recently at the Swiss Federal Institute of Technology (ETH) in Zurich for a symposium on prion diseases in honor of Prof. Charles Weissmann, one of the pioneers in prion research. The symposium, co-sponsored by Prionics, provided an excellent overview of the recent advances in prion research indicating that the interest in this field remains undiminished.
Professor Weissmann's activities in prion research began more than 20 years ago with the cloning of the prion protein by Dr. Bruno Oesch, a co-founder of Prionics, and at that time a Ph.D. student in Weissmann's lab. Throughout his career, Prof. Weissmann has published numerous papers on prion research during his time in Zurich, the U.K. and more recently at his current position at the Scripps Research Institute in Florida, USA. To honor the contributions made by Professor Weissmann to prion research, Life Science Zurich - an organization of the ETH and the University of Zurich - recently held a symposium on prion diseases.
Keynote speech
The scientific program of the symposium was conceived by Professor Adriano Aguzzi of the University Hospital Zurich, who in his opening address gave an overview of the history of prion research and acknowledged the outstanding work by Charles Weissmann's lab. The highlight of the 2-day symposium was the keynote speech by Prof. Weissmann. Notably, the 75 year old prion researcher did not speak about his past research, but instead presented the recent results of his ongoing research on the propagation of prion strains in cultured cells.
Pre-replication prion strain discrimination
Contrary to the common theory that the selective conversion of prion proteins is determined by the malignant scrapie prion PrPSc, during the replication step, Weissmann's data indicate that prion strain discrimination may happen rather at the pre-replication stage. Earlier research had already shown that prion propagation occurs inside the cell and the uptake of PrPSc is probably non-specific. With inhibitors of glycosylation, Weissmann's researchers have been able to block prion propagation of some prion strains in a cell line, whereas others are not affected. Moreover, the effect was only observed when the glycosylation was blocked before or in an early stage of infection. As soon as the first misfolded prions had been formed, gylcosylation inhibitors no longer had an effect, indicating that the glycosylation status of the prion protein itself does not influence prion replication. These results led Weissmann to the hypothesis that a cell-type specific glycosylated protein acts as a prion strain selector and strains replicate differentially depending on the glycosylation status of a cell. This hypothesis could also explain why the brain regions where prions accumulate vary so substantially between infecting prion strains.
