Refining WNT/b-Catenin signalling network in Petri-net model
|Refining WNT/b-Catenin signalling network in Petri-net model|
|Student name:||student name::Matthias Seenok|
|Second supervisor:||Annika Jacobsen|
|Second reader:||has second reader::Annika Jacobsen|
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. 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.
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