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Abstract

Yeast is used as a model system to study the molecular biology, the physiology and the dynamics of cellular stress response. The signaling process and the cellular response constitute a highly interconnected network. The understanding of its performance demands for the application of methods of systems biology, i.e. an integrated investigation of both the subsystems and the network properties based on the present knowledge of the pathway structure and experimental data. A mathematical modeling approach is applied to the systemic response of yeast cells due to stress-induced activation of signal transduction and alteration of gene expression. Here, we consider the response to high osmolarity and to pheromones. The modeling comprises (i) the activation of a membrane-located receptor, (ii) the mediation of the signal via G-Proteins or phosphorelay systems and MAP kinase cascades, (iii) the activation of transcription factors and the alteration of the expression of selected genes, and (iv) the adjustment of metabolism or cell cycle machinery. The model is used to analyze (i) the transmission of the signal through the system, (ii) the signal termination and the role of feedback inhibition, and (iii) the integration and separation of different signal in the process of the cellular adaptation. It can also be used for predicting the outcome of yet unexecuted experiments including the variation of stimulus strength and the test for the behavior of mutants.