Herman, Dorota (2012)
Ph.D. thesis, University of Birmingham.
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Plasmids RK2 are broad host range plasmids and they carry genes for antibioticresistance. Their central control operon, encoding two global regulators KorA and KorB, is anatural example of a negatively self-regulated operon. The aim of the work described herewas to use mathematical models to better understand the function and adaptation of KorA and orB regulation, in the context of available experimental data.
The deterministic models combined with statistical inference allowed for analyses of he regulation mechanism and hypothesis generation about the system dynamics. Furthermore, the extended model was applied to data from different plasmid hosts, in order to indentify processes that might cause a difference in KorB abundance between the hosts.
The stochastic multi-scale models were constructed and used in order to understand evolutionary reasons for such a negative and cooperative autoregulation. The system was tested for optimizations in mRNA production, response time, fluctuation and robustness. Moreover, the effect of cooperative regulation on the response time of the switch between vegetative and conjugative transfer, was also tested.
In conclusion, the studies have deepened our understanding of the model plasmid RK2, of negative and cooperative regulation more generally, and generated hypotheses suitable for experimental validations
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