Research and teaching
There are an increasing number of neurodegenerative disorders which result from the aggregation of misfolded proteins. Prion diseases are unique in this group as they are infectious disorders found in man and animals. It is mandatory to understand the molecular and cellular requirements for propagation and transmission of prions in order to device rational strategies for controlling these events. The long-term goal of our group is to develop therapeutic and prophylactic anti-prion strategies. The overall objective we have is to study the cellular and molecular biology of prion infections and to use gained understanding for delineating novel targets for intervention. One of our central hypotheses is that it is feasible to interfere in prion propagation by increasing the cellular clearance for prions.
Our future work will substantiate our finding that prion clearance can be enhanced by induction of autophagy, a basic cellular program for degradation and recycling. We have also found that a basal level of autophagy is needed for establishing prion infection and we propose that autophagy represents the biological equivalent for the postulated ‘disaggregase’ function in mammalian prion/prion-like biology.
Another pathway we focus on is quality control mechanisms in the secretory pathway which modulate PrP maturation and PrPSc formation. Another main area of our ongoing research is based on the finding that it is possible to overcome self-tolerance against prion proteins by using dimeric/oligomeric recombinant prion proteins as immunogen. Using oral delivery strategies, we want to apply such active vaccination as a prophylactic tool against CWD infections, reducing thereby the spread of CWD within cervids and reduce the risk for a zoonotic transmission in the future. Overall, our studies will provide mechanistic insights into basic molecular mechanisms which are relevant for neurodegenerative diseases and will result in novel targets for therapy against prion diseases and protein misfolding disorders.