Mathematical modelling and systems analysis of intracellular signalling networks and the budding yeast cell cycle

• Main Author: Seaton, Daniel
• Other Authors: Krishnan, J.
• Published: Imperial College London 2013
• Subjects: 660
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.616828

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.