Modellering av SUC2-responsen i Snf1-signalvägen hos S. cerevisiae efter extern glukosminskning

Abstract

The Snf1 pathway is an important part of the nutritional signaling network in yeast. In this project the Snf1 pathway in S. cerevisiae was investigated using mathematical modelling. Four different models of the expression of the invertase SUC2 after a shift in the external glucose concentration from 4 % to 0.1 % were created. In addition to Snf1 and SUC2 the modelled pathway also includes the transcription factor Mig1. The models were made using ordinary differential equations. In order to validate the models they were fitted to experimental data. The first two models, model 0 and model 1, did not accurately describe the observed behavior of the expression of SUC2 and were not analysed further. The other two models, however, did. These were named the X-models, and are two simplifications of the same model, reduced to become structurally identifiable. In the X-models Snf1 was black boxed and all the unknown factors affecting the expression of SUC2 were lumped together in the state variable X. One of the X-models, the lightly reduced version, captured the observed behavior in the beginning of the experiment, whereas the other X-model, the heavily reduced version, captured the stabilization of the expression of SUC2 which occured by the end of the experiment. Residual analysis was performed on the X-models and in order to investigate their ability for prediction a numerical identifiability analysis was initiated. This, however, failed, as the Hessian approximations could not be used to calculate the covariance matrices.