Dr Simone Frey

A Systems Biology Approach for the AMPK/SNF1 Pathway

"I am interested in mathematical modelling of signal transduction pathways and have been working on modelling the Snf1 Pathway."

Systems biology studies the dynamics of intra- and intercellular processes that determine cell function applying mathematical modelling to manage this organized complexity. The questions we focus on are: How is the regulation of Snf1 achieved: through glucose regulated kinase and constant phosphatase, or through a glucose regulated phosphatase and a constant kinase, or even through both being glucose regulated?
Identifying dynamic interactions among components of signaling pathways leads to the understanding and characterization of their effect on the cellular behaviour. Malfunctions in those processes can lead to diseases, such as diabetes type two. Eventually, a defined model might serve as starting point to discuss potential drug targets.

In collaboration with experimentalists, a stimulus response system comprising Snf1 as a key component was selected, along with a manageable number of snf1-interrelating components. This choice mainly depends on the feasibility to generate quantitative time series data. Several experiments were done, including Mig1-GFP intensities and Snf1P Western Blots in a wild type strain as well as in strains that over-expressed the kinase, the phosphatase, or both. In parallel, several model scenarios were defined on an ODEs based framework and compared to the experimental data.

The originally selected system, comprising only kinase, phosphatase and substrates, turned out to be insufficient for describing the data. Considering a more detailed structure or adding further components have become inevitably. Regulation of Snf1 by only its kinase can be discarded. It seems that the data available is not sufficient for excluding one of the two remaining model assumptions.