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Deterministic and stochastic modelling of transcriptional regulation of plasmid RK2

Herman, Dorota (2012)
Ph.D. thesis, University of Birmingham.

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Abstract

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

Type of Work:Ph.D. thesis.
Supervisor(s):Stekel, Dov and Thomas, Christopher M.
School/Faculty:Colleges (2008 onwards) > College of Life & Environmental Sciences
Department:School of Biosciences
Subjects:QR Microbiology
QR355 Virology
Institution:University of Birmingham
ID Code:3720
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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