We also address the question how signalling pathways can reliably transfer and process information by theoretical approaches using generic mathematical models (1,4,5,6,7,8) or detailed realistic kinetic models (2,3). Presently, we work on two different aspects: Firstly, we develop a framework to link techniques from modular response analysis and stochastic analysis to analyse noise propagation in signalling networks (with Frank Bruggeman, Amsterdam). Secondly, we simulate the evolution of signalling networks performing a given task (e.g. regulating a metabolic network under varying conditions). In this project we aim to identify network designs that evolved to be robust with respect to typical variation of e.g. protein levels.

Collaboration with theoretical groups: H. Westerhoff (Manchester), H. Herzel (Berlin), F. Bruggeman (Amsterdam), B.N. Kholodenko (Philadelphia)

1. Blüthgen N, Legewie S: Systems analysis of MAPK signal transduction. Essays in Biochemistry 2008, in press
2. Legewie S, Schoeberl B, Blüthgen N, Herzel H: Competing Docking Interactions Can Bring About Bistability in the MAPK Cascade. Biophys J 2007, 93:2279-2288
3. Legewie S, Blüthgen N, Herzel H: Mathematical modeling identifies inhibitors of apoptosis as mediators of positive feedback and bistability. PLoS Comput Biol 2006, 2(9):e120
4. Blüthgen N, Bruggeman FJ, Legewie S, Herzel H, Westerhoff HV, Kholodenko BN: Effects of sequestration on signal transduction cascades. FEBS J 2006, 273(5):895-906.
5. Blüthgen N: Sequestration shapes the response of signal transduction cascades. IUBMB Life 2006, 58(11):659-663
6. Legewie S, Blüthgen N, Schafer R, Herzel H: Ultrasensitization: switch-like regulation of cellular signaling by transcriptional induction. PLoS Comput Biol 2005, 1(5):e54.
7. Legewie S, Blüthgen N, Herzel H: Quantitative analysis of ultrasensitive responses. FEBS J 2005, 272(16):4071-4079.
8. Blüthgen N, Herzel H: How robust are switches in intracellular signaling cascades? J Theor Biol 2003, 225(3):293-300.