Controlling chemotaxis: A study on novel migration behaviours in multi-signal systems

Dowdell, Adam Oliver Duncan (2022) Controlling chemotaxis: A study on novel migration behaviours in multi-signal systems. PhD thesis, University of Glasgow.

Abstract

Directed cell motility plays a crucial role at some stage for most forms of life. Single celled organisms rely on finely controlled motion to hunt or migrate toward optimum environmental conditions. Multicellular organisms require a continual system of simultaneous - and precise - cellular migration, from conception until death, simply in order to develop and survive. These migrations are most often modulated via diffusible extracellular signals, causing the affected cell to move towards or - rarely - away from the source of the signal; this is chemotaxis. The primary aim of this thesis is to come to a fundamental understanding of the relationship between chemotactic signals and the elicited cellular response, from basic singular signals to complex multi-signal systems, and use this knowledge to predict novel migration behaviours. This is achieved using a feedback loop between an iterative process of mathematical modelling, to predict chemotactic responses, and live cell imaging, to validate and improve upon the model. Assays are performed using Insall chambers, a direct visualisation chemotaxis chamber, and the motile amoeba Dictyostelium discoideum. A diverse range of extracellular signalling conditions are constructed via the varying chemotactic properties of different derivatives of cAMP, a signalling molecule to which D. discoideum are highly chemotactic. Using mathematics as an interface between chemical concentration and subsequent cell-surface receptor activation, many complex migration behaviours were predicted and experimentally verified. Of particular interest are: a robust system by which chemorepulsion - the mechanics of which have been elusive - can be mediated, conditions that can give rise to an inversion of chemotactic directionality in the same gradient, and proof that two signals that cause chemoattraction in isolation can be combined to induce chemorepulsion.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: R Medicine > RC Internal medicine; R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Colleges/Schools: College of Medical Veterinary and Life Sciences
• Supervisor's Name: Insall, Professor Robert
• Date of Award: 2022
• Depositing User: Theses Team
• Unique ID: glathesis:2022-83304
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 12 Dec 2022 12:17
• Last Modified: 13 Dec 2022 12:17
• Thesis DOI: 10.5525/gla.thesis.83304
• URI: https://theses.gla.ac.uk/id/eprint/83304