Refining WNT/b-Catenin signalling network in Petri-net model

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Refining WNT/b-Catenin signalling network in Petri-net model
status: ongoing
Master: project within::Bioinformatics
Student name: student name::Matthias Seenok
Start start date:=2013/04/01
End end date:=2013/08/01
Supervisor: Anton Feenstra
Second supervisor: Annika Jacobsen
Thesis: has thesis::Media:Thesis.pdf
Poster: has poster::Media:Posternaam.pdf

Signature supervisor



The GPCR signalling network is of paramount interest in basic biological understanding of cell behaviour, and due to its intimate connections with processes like cell cycle, differentiation, and many others, also has profound implications for pharmacological applications.

The project will investigate the feasibility of encoded GPCR signaling pathways or networks as a Petri-net model, based on our recent work in developmental differentiation in C. elegans[1][2]. The Petri-net model will be calibrated for 'appropriate' behaviour, e.g., absence of asymptotic or lifeless behaviour starting from a number of initial conditions. Further fine tuning against known behaviour of the system will be performed. Part of the calibration and fine tuning may need to be done manually, but the intention is to apply genetic algorithms (GA) to automate this otherwise labour-intensive process. The efficacy of GA for this purpose will also be assessed.

For a specific biological signaling network, involving GPCR receptor proteins, a matrix is available describing detailed interactions between the 50 or so different types of molecules involved, that has been used in a propriatory model. Another GPCR signaling system is available for this modeling work at the VU from the group of Martine Smit, which opens the option of follow-up experiments for particularly interesting model predictions.


  1. Krepska E, et al. 2008 Krepska E, Bonzanni N, Feenstra KA, Fokkink W, Kielmann T, Bal H, Heringa J. Design issues for qualitative modelling of biological cells with Petri nets. In: Proceedings of the Formal Methods in Systems Biology 2008 (2008) 5054. Cambridge, UK: Springer. 48–62. of LNBI.
  2. Bonzanni et al. 2008 Bonzanni N, Krepska E, Feenstra KA, Fokkink W, Kielmann T, Bal H, Heringa J. Executing Multicellular Differentiation - Quantitative Predictive Modelling of C elegans Vulval Development Bioinformatics. 2009 25:2049-56.

Further Reading

  • Musnier et al., 2010 Musnier A, Blanchot B, Reiter E, Crépieux P. GPCR signalling to the translation machinery. Cell Signal. 2010 22:707-16.
  • Musnier et al, 2009 Musnier A, Heitzler D, Boulo T, Tesseraud S, Durand G, Lécureuil C, Guillou H, Poupon A, Reiter E, Crépieux P. Developmental regulation of p70 S6 kinase by a G protein-coupled receptor dynamically modelized in primary cells. Cell Mol Life Sci. 2009 66:3487-503.
  • Bromberg et al. 2008 Bromberg KD, Ma'ayan A, Neves SR, Iyengar R. Design logic of a cannabinoid receptor signaling network that triggers neurite outgrowth. Science. 2008 320:903-9.
  • Neves et al., 2008 Neves SR, Tsokas P, Sarkar A, Grace EA, Rangamani P, Taubenfeld SM, Alberini CM, Schaff JC, Blitzer RD, Moraru II, Iyengar R. Cell shape and negative links in regulatory motifs together control spatial information flow in signaling networks. Cell. 2008 133:666-80.
  • Ruths et al., 2008 Ruths D, Muller M, Tseng JT, Nakhleh L, Ram PT. The signaling petri net-based simulator: a non-parametric strategy for characterizing the dynamics of cell-specific signaling networks. PLoS Comput Biol. 2008 4:e1000005
  • Slinger et al., 2010 Erik Slinger, Ellen Langemeijer, Marco Siderius, Henry F. Vischer, Martine J. Smit. Herpesvirus-encoded GPCRs rewire cellular signaling Molec Cell Endocr. 2010 (in press)