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
Dates
Start start date:=2013/04/01
End end date:=2013/07/01
Supervision
Supervisor: Anton Feenstra
Second supervisor: Annika Jacobsen
Second reader: has second reader::Annika Jacobsen
Thesis: has thesis::Media:Thesis.pdf
Poster: has poster::Media:Posternaam.pdf

Signature supervisor



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Abstract

The b-Catenin/WNT 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 build upon previous work that established the feasibility of encoding the WNT/b-Catenin signaling network as a Petri-net model, based on our eariler work[1][2]. The existing Petri-net model was calibrated for 'appropriate' behaviour, e.g., absence of asymptotic or lifeless behaviour starting from a number of initial conditions.

In the current project, further fine tuning of this model against known behaviour of the system will be performed. In addition, a minimalistic 'canonical' model has been constructed that only reproduces the 'basic' behaviour of activation of the TCF-LEF transcription factor by addition of the WNT ligand binding to the Frizzled receptor. This minimalistic model will be further explored, and incremental additions (in components or in detail or sophistication of the existing components) will be made to incorporate components and behaviour of interest. These additions and their characteristics will be based on available experimental and/or literature date where available. Together, this should lead to a better understanding of the mechanisms active in this signalling pathway.

Related Projects

Implementing GPCR signaling network model in Petri-Net (Michiel Vegt)

References

  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)