Mathematical modelling and systems analysis of intracellular signalling networks and the budding yeast cell cycle
Author(s)
Seaton, Daniel
Type
Thesis
Abstract
Cellular signalling networks are responsible for coordinating a cell’s response to internal
and external perturbations. In order to do this, these networks make use of a wide variety
of molecular mechanisms, including allostery, gene regulation, and post-translational
modifications. Mathematical modelling and systems approaches have been useful in understanding
the signal processing capabilities and potential behaviours of such networks.
In this thesis, a series of mathematical modelling and systems investigations are presented
into the potential regulation of a variety of cellular systems. These systems range
from ubiquitously seen mechanisms and motifs, common to a wide variety of signalling
pathways across many organisms, to the study of a particular process in a particular cell
type - the cell cycle in Saccharomyces cerevisiae.
The first part of the thesis involves the analysis of ubiquitous signalling mechanisms
and behaviours. The potential behaviours of these systems are examined, with particular
attention paid to properties such as adaptive and switch-like signalling. This series of
investigations is followed by a study of the dynamic regulation of cell cycle oscillators by
external signalling pathways. A methodology is developed for the study of mathematical
models of the cell cycle, based on linear sensitivity analysis, and this methodology is then
applied to a range of models of the cell cycle in Saccharomyces cerevisiae. This allows the
description of some interesting generic behaviours, such as nonmonotonic approach of cell
cycle characteristics to their eventual values, as well as allowing identification of potential
principles of dynamic regulation of the cell cycle.
and external perturbations. In order to do this, these networks make use of a wide variety
of molecular mechanisms, including allostery, gene regulation, and post-translational
modifications. Mathematical modelling and systems approaches have been useful in understanding
the signal processing capabilities and potential behaviours of such networks.
In this thesis, a series of mathematical modelling and systems investigations are presented
into the potential regulation of a variety of cellular systems. These systems range
from ubiquitously seen mechanisms and motifs, common to a wide variety of signalling
pathways across many organisms, to the study of a particular process in a particular cell
type - the cell cycle in Saccharomyces cerevisiae.
The first part of the thesis involves the analysis of ubiquitous signalling mechanisms
and behaviours. The potential behaviours of these systems are examined, with particular
attention paid to properties such as adaptive and switch-like signalling. This series of
investigations is followed by a study of the dynamic regulation of cell cycle oscillators by
external signalling pathways. A methodology is developed for the study of mathematical
models of the cell cycle, based on linear sensitivity analysis, and this methodology is then
applied to a range of models of the cell cycle in Saccharomyces cerevisiae. This allows the
description of some interesting generic behaviours, such as nonmonotonic approach of cell
cycle characteristics to their eventual values, as well as allowing identification of potential
principles of dynamic regulation of the cell cycle.
Date Issued
2012-12
Date Awarded
2013-07
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
License URL
Advisor
Krishnan, J
Sponsor
Engineering and Physical Sciences Research Council
Publisher Department
Chemical Engineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)