Pontus Melke
Modeling the TGF-beta Signaling Pathway in Endothelial Cells

Master Thesis in Theoretical Physics

Advisors: Henrik Jönsson and Carsten Peterson

Abstract:
We have developed a mathematical model of the TGF-beta pathway in endothelial cells. This pathway plays a prominent role for basic cellular functions, as well as for almost all forms of human cancers. The model successfully describes experimental data, correctly predicts "blind-test" experiments and it provides experimentally testable predictions. Moreover, we have developed tools for analyzing sensitivity properties of biological networks. Such an analysis further improves our understanding of the pathway by identifying critical parameters as well as finding those crucial for robustness. Comparing sensitivity properties of the TGF-beta pathway to those of a simpler model, reveals that the negative feedback loop in TGF-beta signaling renders the system stability. Thus, the negative feedback loop is a mean of achieving robustness against perturbations such as temperature fluctuations, fluctuations in interior and exterior molecule concentrations, and mutations.

LU TP 04-44, January 2005