Seminars

IncP1 plasmids are broad host range plasmids that have been isolated in clinical and environmentally occurring bacteria. They have a well-characterized genome, encoding genes for vegetative replication, stable maintenance, active partitioning and conjugative transfer, controlled by 7 transcription factors. In this work, we develop mathematical models for the auto-regulation of the central control operon that codes for the plasmid's global regulators KorA and KorB. We seek to answer a series of questions: (i) why has evolution selected an intricate regulatory mechanism, consisting of two, dimeric, cooperative, self-regulating transcription factors? (ii) are the experimental data compatible, specifically the high level of protein relative to the operator binding strength and can more than one hypothesis explain the data? (iii) which of the unknown parameters of the system can be estimated, and which might be important to measure?; (iv) how do statistical inference and metabolic control theory compare as methods of determining importance of parameters? We apply a range of modeling techniques, including deterministic, stochastic and multi-scale approaches to answer these questions.