The effects of stochasticity and population structure on mathematical descriptions of evolutionary dynamics
Lead Research Organisation:
UNIVERSITY COLLEGE LONDON
Department Name: Mathematics
Abstract
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Organisations
Publications
Renton J
(2019)
Evolution of cooperation in an epithelium.
in Journal of the Royal Society, Interface
Renton J
(2021)
Cooperative success in epithelial public goods games.
in Journal of theoretical biology
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509577/1 | 30/09/2016 | 24/03/2022 | |||
| 1777631 | Studentship | EP/N509577/1 | 30/09/2016 | 12/05/2021 | Jessica Renton |
| Description | Cancer occurs when cells in the body mutate and invade healthy tissues forming tumours. Our work looks at the early stage of this process, considering the likelihood of invasion when a single cell acquires a mutation. This is dependent on several factors including the type of mutation, the structure of the tissue and the specific mechanisms for cell division and death. We have focussed on epithelia, the tissues which form surfaces in the body such as skin, which are the origin point for most cancers. Previous work has used evolutionary graph theory to model evolution in these systems. We have instead used an explicit model of an epithelium called the Voronoi tessellation model, which has the advantage that the population structure is not fixed and there is more flexibility in how divisions and deaths can be implemented. We have looked at cooperative mutations, whereby mutated cells do not boost their own fitness directly, but provide a benefit to their neighbours. We have found that the spatial coupling of division and death events plays an important role in the success of cooperative mutations. When there is no interdependence of the locations of divisions and deaths, cooperation is more successful. Conversely, when divisions are constrained to occur only in cells neighbouring a recent death cooperation is less successful. Furthermore, if we implement density-dependence of proliferation, whereby cells can only divide if they exceed a certain size threshold, there is a spectrum of behaviour between these extremes. We find that the success of cooperation depends not only on the spatial coupling of death and division, but additionally, on mechanical properties of the epithelium. In healthy epithelia there is a strict balance maintained between divisions and deaths in order that population size remains constant. This process is still being understood, however density-dependent death and division play a role. Therefore it is likely that division and death are spatially coupled. Understanding these processes and how they affect evolutionary outcomes could therefore be important for modelling oncogenesis. |
| Exploitation Route | Our results show the importance of taking into account population structure and spatial coupling of birth and death when modelling evolution in epithelia. It is therefore important that models which seek to predict cancer evolution and outcomes should factor in these results. Furthermore our results should be taken into account when using modelling to evaluate potential efficacy of cancer therapies. Our results are also relevant to studies of cooperation in cell populations beyond cancer, and to microbial populations that produce diffusible public goods. |
| Sectors | Healthcare Pharmaceuticals and Medical Biotechnology |
| URL | https://github.com/jessierenton |
| Description | Sir George Jessel Studentship |
| Amount | £1,800 (GBP) |
| Organisation | University College London |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 02/2019 |
| End | 02/2019 |