Abbadi, Mohammad Daoud Omar; (2020) Modelling and analysis of the control mechanisms of bacterial growth. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis concerns the control mechanisms of bacterial growth. Mathematical and experimental work has shown the control of bacterial growth behaves like a switch. It is known that the vitamin B12 riboswitch plays a role in this switching mechanism. These facts motivate considering variable structure control techniques to investigate the control mechanism and the robustness of the riboswitch. Whilst the existence and importance of switches are widely acknowledged within the biological literature, many life scientists do not deal explicitly with the switching behaviour. Frequently, steady-state behaviour before and after switching is the primary focus. The main objective of this thesis is to study the control mechanisms of the vitamin B12 riboswitch on bacterial growth at both a cellular and population level. The results using different bacterial strains show that changing the concentration of vitamin B12 affects growth until the saturation level is reached. The thesis then studies the control mechanism in algal and bacterial co-culture. A model has been developed using data from an in vivo experimental two-species system where the bacterium Mesorhizobium loti (M. loti) supplies the vitamin B12 required for growth to the freshwater green alga Lobomonas rostrata (L. rostrata) and where the action of the B12 riboswitch is known to be a determinant of system behaviour. The reachability analysis from sliding mode control is used to find the algal and bacterial saturation level and study the robustness of the system. Using the validated riboswitch model, an observer design method from the domain of control engineering is used to estimate the vitamin B12 transporter BtuB given measurements of the concentration of vitamin B12. Validation of the estimates of BtuB has been undertaken by comparing the relationship between the BtuB and vitamin B12 concentrations estimated from the observer with the relationship between green fluorescent protein production and the concentration of vitamin B12 obtained experimentally.

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