Understanding the dynamics of biological networks through minimal switches and timekeepers

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Bistability and limit cycles are two recurrent dynamics observed in decision-making systems, which may lead to either switch-like or oscillatory behaviours. The properties of these dynamics are exploited by relevant biological networks, such as the cell cycle or circadian rhythms. Due to the complexity of these networks, different approaches have been developed to investigate their dynamical properties. In this thesis, I tackle the understanding of these complex dynamics through the development of minimal networks. Besides, to unveil hidden dynamical properties of complex networks, I make use of the network emulation technique. This technique is a recent approach by which complex networks are impersonated by others that emulate their dynamical behaviour to facilitate their analysis. This approach has been successfully applied to investigate the dynamical properties of biological networks that behave as switches. One of the networks studied is the regulatory network of the cell cycle.
This research expands on the previous investigation of the cell cycle regulatory network. As starting point, I use the network emulation technique to tackle the dynamical differences between biochemical type and biological function of the mitotic onset. This technique has proved to be useful to reveal complex networks with switch-like behaviours. However, the network emulation technique is constrained to this type of behaviour due to the lack of minimal networks with diverse dynamics. Thus, part of this research is focused on expanding this technique to include other relevant biological dynamics. Concretely, I develop a minimal network displaying an oscillatory behaviour that will be use as base to expand the technique into oscillatory dynamics. Moreover, I also show that the minimal networks with switch-like dynamics are linked to the development of minimal networks with oscillatory behaviours.
Being this thesis a theoretical research, diverse mathematical models have been developed and systematically analysed from the dynamical point of view. The dynamical analysis has been conducted through a pipeline of functions in R that I have implemented.
Date of Award2018
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorAttila Csikasz-Nagy (Supervisor) & Luca Cardelli (Supervisor)

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