Within the Graduate School, the analysis of characteristics and requirements of regenerative systems and the evaluation of the developed concepts are based on a concrete biological regenerative system: the Wnt signalling pathway and its significant role in the differentiation of neuronal stem cells. Dysfunction of the Wnt pathway can yield serious consequences like pathological diseases such as Parkinson’s disease and Cancer.

In a Systems Biology approach, together with experimental partners within the research school, we developed a mathematical model of the Wnt signalling pathway. Thereby we focused on the main protagonist ß-catenin and its antagonists APC, Axin and GSK3, which control its cytoplasmic degradation. The investigation of several hypotheses about their particular cellular distribution led to the design of new experiments.

The canonical Wnt Signalling pathway. In cells not exposed to the Wnt signal, ß-catenin interacts with a complex make of APC, Axin and GSK, which phosporylates it and thereby marks it for proteasomal degradation. Hence, cytosomal ß-catenin levels are kept low. When a cell receives a Wnt signal, the Wnt protein interacts with the receptor complex LRP/Frz. The signal is further transducted via Dsh, which leads to an inhibition of degradation. The stimulus hence induces cytoplamic stabilization and nuclear translocation of ß-catenin. In the nucleus, ß-catenin acts as a transcriptional co-factor: its interaction with TCF promoters controls description and target gene expression.