Development and validation of a humanized Schizosaccharomyces pombe yeast model for the study of tau-mediated cytotoxicity.

In this research project the use of a new complementairy humanised yeast model to study the fundamental aspect of Tau pathology, will be introduced; the fission yeast Schizosaccharomyces pombe. Tau toxicity is crucial in the development of a certain class of neurodegenerative diseases, the tauopathies, of which Alzheimer's disease is an important example. The main reason for the choice of this new yeast model is the fact the preliminary results indicate that expression of wt Tau in S. pombe cells leads to the formation of Tau inclusions, visually observable, and a Tau-dependent toxicity in normal growth conditions, and this in contrast to the budding yeast Saccharomyces cerevisiae.                                

The first goal of this project is to further develop and validate this S. pombe model as a complementary model system for the study of the fundamental aspect of Tau pathology. Secondly, the cellular mechanisms involved in Tau-mediated cytotoxicity will be elucidated. Finally, the interaction between Tau and other tauopathy players will be studied. 

Therefore, this project has the potential to contribute to the development of more accurate diagnostic tests, e.g. through the identification of novel biomarkers or the development of new monoclonal antibodies. In addition, biological modulators of Tau oligomersation and pathogenesis could be identified, which can lead to the characterisation of new drugable targets and lead compounds which can be of use in therapeutic treatments.