Mazemondet, Orianne (2011) Spatio-temporal Dynamics of the Wnt/ß-catenin Signaling Pathway: A Computational Systems Biology Approach. PhD thesis, Institute of Computer Science, University of Rostock.
Full text not available from this repository.Abstract
Human neural progenitor cells (hNPCs) are a new prospect for neuron replacement therapy in the context of neurodegenerative diseases, e.g. Parkinson’s disease. ReNcell VM cells are hNPCs cultured in vitro that allow to investigate and understand the mechanisms of neuron dif- ferentiation, before clinical studies can be performed. The Wnt/β-catenin signaling pathway is involved in ReNcell VM cell differentiation. A first step to understand its role in this biological process is to investigate the spatio-temporal dynamics of its signaling proteins. This dissertation employs the cyclic workflow of computational systems biology, deploying both wet- and dry-lab experiments, to investigate the spatio-temporal dynamics of Wnt/β-catenin pathway in ReNcell VM cells. By means of cellular and molecular biology techniques, quantitative kinetic analyses of the pathway’s signaling proteins are performed. These show biphasic kinetics during the first three days of physiological differentiation. A computational model of ReNcell VM cell population is developed to investigate in silico the sources of the biphasic kinetics observed in vitro. The in silico experiments describe the impact of the cell asynchrony w.r.t. the cell cycle on the protein dynamics and give insights about the role of self-induced Wnt signaling in the cell population. A stochastic investigation reveals discrepancies in the deterministic approximation and emphasizes the importance of stochastic approaches for modeling biological systems. We propose additional wet-lab experiments in order to validate the in silico predictions, and hence close the loop of computational systems biology.
| Item Type: | Thesis (PhD) |
|---|---|
| Projects: | GRK dIEM oSiRiS |
