Research Report 2010 - MDC

SecretariatSonja GieringPetra Haink*part of the period reportedIn other projects we investigate cell-type specific differencesin Wnt/β-catenin signaling, analyse the effect oftranscriptional feedbacks (e.g. via Axin, β-TrCP/ HOS)and that of cross-talks of Wnt/β-catenin signaling toother pathways, most importantly NF-κB.Robustness of cellular rhythmsKatharina Baum, Antonio PolitiRhythmic phenomena are widespread in biology andmany examples can be found on the cellular level, e.g.circadian rhythms, the cell cycle, calcium or metabolicoscillations. These rhythms are involved in various functionsand react specifically to environmental changes.Our project addresses the question of what determinesthe balance between sensitivity and robustness of acellular rhythm. To this end we analyse specific examplesof oscillations. By comparing various well-establishedmathematical models for calcium, glycolytic andcircadian rhythms we could already show that the sensitivityof the oscillatory period against perturbationsstrongly depends on the underlying oscillatory mechanism.We now ask the question to what extent robustnessis determined by local kinetic parameters or thetopology of the systems. In our comparison, we findmodels for calcium oscillations to be very sensitive,those for circadian rhythms very robust. These findingscorrespond well to the biological functions of therhythms since for calcium oscillations a period-encodedsignal-transduction was shown, whereas circadianoscillations generate an internal time information. Inaddition, the effect of the feedback type on the sensitivityis studied in core models.Comparison of the period sensitivity of cellular oscillators.Shown is the overall period sensitivity of ten mathematicalmodels describing three cellular rhythms. Models for calciumoscillations are very sensitive, those for circadian rhythm arevery robust. Models for glycolytic oscillations show an intermediatesensitivity.Selected publicationsJ. Wolf, S. Dronov, F. Tobin & I. Goryanin (2007), The impact of theregulatory design on the response of EGFR-mediated signal transductiontowards oncogenic mutations. FEBS Journal 274, 5505-5517.J. Wolf, S. Becker-Weimann & R. Heinrich (2005), Analysing the robustnessof cellular rhythms, IEE Syst. Biol. 2(1), 35-41.S. Becker-Weimann, J. Wolf, H. Herzel & A. Kramer (2004), Modelingfeedback loops of the mammalian circadian oscillator. BiophysicalJournal 87, 3023-3034.Cardiovascular and Metabolic Disease Research 61