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Title: Modelling the intracellular NF-κB signalling pathway
Author: Pogson, Mark
ISNI:       0000 0004 2691 517X
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2006
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NF-κB is a transcription factor which is central to the regulation of genes involved in inflammatory and immune responses. Understanding the operation of NF-κB and its associated intracellular signalling pathway is essential in order to control a wide range of chronic inflammatory diseases, including asthma and rheumatoid arthritis. Abnormalities in the pathway are present in a variety of human cancers and may also affect the pathogenesis of Alzheimer's disease. Computational modelling of the signalling pathway is necessary to overcome the practical limitations of biological experiments and to facilitate a more comprehensive understanding of the system. The thesis begins by outlining existing understanding of the NF-κB signalling pathway, which in conjunction with a review of modelling methods is used to inform a different approach to model the pathway, using computational agents to represent individual molecules and receptors. The agent-based model is tested with well-understood chemical reactions before being used to describe the pathway. This provides a good appreciation of the system as a whole, offering a detailed description of events at every step in the pathway and allowing investigation of stochastic, spatial and structural parameters. The modelling process and simulation help to provide a prediction about the role of actin filaments of the cytoskeleton in regulating the unstimulated pathway; this is quantitatively validated by biological experiment. The effect of cell shape on the pathway is also investigated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available