Towards Whole Cell “in Silico” Models for Cellular Systems: Model Set-up and Model Validation

Abstract

Based on recent developments for new measurement technologies that enable researches to get quantitative information on intracellular processes, the setup 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 computer based 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 simulation 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. These units are members of the crp modulon and are under control of a global signal transduction system which calculates the signals that turn on or off gene expression for the specific enzymes. Problems of parameter identification for whole cell models are discussed.