This thesis develops and analyses an agent based model of a bacterial Eschericia coli population in a quorum motivated by published experimental work The E. coli cells harbour a synthetic genetic regulatory network that is responsible for oscillatory behaviour across the population. The model is used to understand whether the collective oscillations seen in the experiments are an outcome of coupled oscillators synchronising or if they are an emergent property of the population. A bottom-up approach is used whereby an ordinary differential equation model is developed based on the biochemical dynamics that result from the introduced genetic network This model is studied using numerical bifurcation analysis, from the single cell level to see whether oscillatory behaviour exists and if such behaviour persists when groups of coupled cells are considered. Subsequently, the model is extended and an explicit spatial dimension is included to study any spatiotemporal effects that can affect the nature of oscillations. The spatial model is implemented in BSim, a novel software platform developed in Bristol, by students of the Bristol Centre for Complexity Sciences, to study bacterial population dynamics in silica. Finally, we study the possibility of controlling the cellular population, an area that has received a lot of attention recently in cellular biology. Specifically, we compare the performance of open and closed loop control in entraining the population to follow a non-native oscillating period. Vve also compare the ability to make the population track a non-oscillating signal. Our results indicate that the oscillatory behaviour seen in the published experiments is an emergent population level property. The onset and synchronisation of oscillations are dependent on cell density and the speed of diffusion of the coupling chemical in the environment medium. Also, the oscillating population is best controlled with closed loop methods.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:628994 |
| Date | January 2013 |
| Creators | Mina, Petros |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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