Cell signaling: a systems approach

Abstract: All higher functions of the cell are dependent on cell signaling. It is the way of the cell to obtain information about the world surrounding it. By getting information on e.g. temperature, glucose concentrations, or the density of neighboring cells, the cell can make decisions on how to optimally act given the supplied information. Even though cells are very different, some of the basic mechanisms governing the signaling are the same everywhere – from the most simple single-cellular bacteria to the cells we ?nd in our bodies. In this thesis we will study cell signaling in three different types of cells: in Paper I we study the TGF-? pathway in endothelial mammal cells, in Paper II and Paper III the bio?lm formation and quorum sensing of bacterial cells, and in Paper IV plant stem cells. We use a combination of rate-equation models, mechanical cell-based models, and statistical tools to study the dynamics of these networks. By this approach we can ?nd and validate hypotheses in cases where mere biological intuition is not enough. We can also indentify key components and modules of the systems, and predict quantities not yet measured. This provides a work ?ow where the model is set up to test hypotheses against available data, the model suggests new experiments which later can be used to further improve the model. The approach of combining experimental data with mathematical modeling has proven to be very fruitful for the understanding of many biological systems.