Bland, Tom;
(2022)
Molecular feedback and self-organisation in the PAR polarity network.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Polarisation of cells by the PAR network bears hallmarks of a self-organising reaction-diffusion network, comprising of two sets of proteins which stably segregate into mutually exclusive membrane-associated domains. A number of nonlinear behaviours, including antagonistic feedback interactions, protein oligomerisation and positive feedback reactions have been proposed to contribute to the maintenance of this stable polarised state, but we lack sufficient insight into the quantitative nature of these interactions to fully understand their contribution to polarity. Furthermore, recent work reveals that PAR protein patterns display striking and unexpected robustness to breakages in this reaction network, implying the existence of additional feedback reactions that we are yet to fully account for. Through quantitative imaging, gene editing, in vitro biochemistry, and mathematical modelling, I have taken an interdisciplinary approach to study the molecular circuitry of feedback reactions in the C. elegans PAR network. Focussing on the posterior PAR subnetwork, my work reveals a novel role for the RING-finger domain of PAR-2 in facilitating concentration-dependent protein dimerisation, which drives stable membrane association and contributes to positive-feedback driven polarity.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Molecular feedback and self-organisation in the PAR polarity network |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. 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. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10154309 |
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