Renton, Jessie;
(2021)
Evolutionary games between epithelial cells: the impact of population structure and tissue dynamics on the success of cooperation.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Cooperation is usually understood as a social phenomenon. However, it also occurs on the cellular level. A number of key mutations associated with malignancy can be considered cooperative, as they rely on the production of diffusible growth factors to confer a fitness benefit. Evolutionary game theory provides a framework for modelling the evolutionary dynamics of these cooperative mutations. This thesis uses evolutionary game theory to examine the evolutionary dynamics of cooperation within epithelial cells, which are the origin point of most cancers. In particular, we consider how the structure and dynamics of an epithelium affect cooperative success. We use the Voronoi tessellation model to represent an epithelium. This allows us much greater flexibility, compared to evolutionary graph theory models, to explore realistic dynamics for population updating. Initially, we consider a model where death and division are spatially decoupled. We analyse pairwise social dilemma games, focussing on the additive prisoner’s dilemma, and multiplayer public goods games. We calculate fixation probabilities, and conditions for cooperative success, by simulation, as well as deriving quasi-analytic results. Comparing with results for graph structured populations with spatially coupled birth and death, or well-mixed populations, we find that in general cooperation is promoted by local game play, but global competition for offspring. We then introduce a more realistic model of population updating, whereby death and division are spatially coupled as a consequence of contact inhibition. The strength of this coupling is positively correlated with the strength of contact inhibition. However, the extent to which strong spatial coupling inhibits cooperation depends on mechanical properties of the tissue.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Evolutionary games between epithelial cells: the impact of population structure and tissue dynamics on the success of cooperation |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| Keywords: | Evolutionary game theory, Epithelial automata, Voronoi tessellation, Cooperation, Somatic evolution |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Mathematics |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10133725 |
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