Development of Cell Models as a Basis for Bioreactor Design for Genetically Modified Bacteria

摘要

The purpose of the project is the development of a mathematical model of the bacterium, Escherichia coli, modified by the insertion of plasmids containing foreign DNA. Such a model provides a basis to simulate on the computer the response of a culture to a variety of environmental stimuli. The results of such simulations can be verified experimentally. This model is formulated to allow the investigator to probe hypotheses concerning cellular regulation and biochemistry. This ability is particularly important with respect to genetically modified cells where the insertion of foreign DNA and expression of foreign genes interacts strongly with host cell physiology in complex and often unpredictable ways. The model should provide, by the completion of the project, useful guidance on how to best construct a plasmid for insertion into E. coli. Not only should be model suggest optimal strategies for construction of strains but should provide the engineer with a tool to better design large-scale systems utilizing cells with recombinant DNA. Major problems in the large scale utilization of plasmid containing cells are genetic instability and maintenance of high levels of gene expression. A model for the control of replication of plasmids with the COLE1 origin of replication has been successfully introduced.