Towards whole cell in silico models for cellular systems : model set-up and model validation

Based on recent developments for new measurement technologies that enable researches to get quantitative information on intracellular processes, the set-up of very detailed models describing metabolism as well as regulatory networks becomes very popular. However, biochemical networks are rather complex including many feed-forward and feedback loops. In this contribution we propose an interdisciplinary approach including the computerbased set-up of models and strategies to validate the models with apparent experiments. This approach will offer a new way to meaningful models that can be used to make simulations experiments analogous to real laboratory experiments. The approach is applied to the bacterium Escherichia coli: A mathematical model to describe carbon catabolite repression is developed and in part validated. The model is aggregated from functional units describing carbohydrate transport and degradation. All units are members of the crp modulon and are under control of aglobal signal transduction system which calculates the signals that turn on or off gene expression for the specific enzymes. Problems for parameter identification of whole cell models are discussed