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Title: Genome-based metabolic modelling of CHO cells
Author: Chen, Ning
ISNI:       0000 0004 2736 869X
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Model-based analysis of cellular metabolism can facilitate our understanding of intracellular kinetics and aid the improvement of cell growth and biological product manufacturing. In this thesis, a model-based kinetic study of cytosolic glucose metabolism is presented. Based on the Kyoto Encyclopedia of Genes and Genomes and the Braunschweig Enzyme Database, a metabolic map of cytosolic glucose metabolism including 30 metabolites and 36 reactions, which consists of glycolysis, glucogenesis, pentose-phosphate pathway and adjacent metabolic reactions, has been constructed. Kinetic modelling was performed according to this metabolic map and reported enzyme kinetic studies, considering regulation and/or inhibition by products, substrates or other metabolites. Parameters were estimated based on previous parameter information and metabolic flux analysis studies, as well as results from our own experiments. Simulation results for cell population kinetics, metabolite concentrations and reaction rates have shown good agreement with experimental data. Furthermore, in silico case studies including global sensitivity analysis, feeding lactate as a co-substrate and the regulation effect by fructose 2,6-bisphosphate were performed in order to find strategies to increase metabolic efficiency in Chinese hamster ovary cells in an attempt to provide a guide for process optimisation. In conclusion, our model provides a deep look into cytosolic glucose metabolism and the simulation results have suggested a suitable direction to increase the metabolic efficiency.
Supervisor: Kontoravdi, Cleo Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral