Esparza Franco, Manuel A. (2016) A systems biology analysis of feedback control in pheromone signalling of fission yeast. PhD thesis, University of Warwick.

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Abstract

Cell signalling comprises the systems used by cells to detect changes in their environment and to transduce the information into appropriate adjustments enforced by regulatory proteins. Due to its central role in all life processes, the study of cell signalling is a major focus of current biomedical research. The fission yeast Schizosaccharomyces pombe (S. pombe) is a single-celled organism used as a model to simplify the study of eukaryotic cell signalling, as it shares many features of interest with human cells. In this thesis a systems biology approach was used to investigate the roles of feedback regulation to control the dynamics of pheromone signalling in S. pombe. To this end, a quantitative dynamical model was built describing the pheromone-induced activation of the master transcription factor Ste11, as well as the coupled positive and negative feedback loops that arise from Ste11 activity. To constrain the model, a collection of data sets were generated by performing absolute quantification measurements of pheromone-dependent changes in the concentration of the model species. Structural identifiability analyses were used to select the measured species, while confidence intervals of the estimated parameters were determined through profile likelihood estimation. Analysis of the resulting model revealed a role for the pheromone signalling feedback loops to aid in the discrimination of different pheromone input doses. Through their combined action, feedback control defines the concentration and time thresholds in Ste11 activity that must be satisfied for the cell to commit to a sexual development fate.

Item Type:	Thesis (PhD)
Subjects:	Q Science > QH Natural history > QH301 Biology
Library of Congress Subject Headings (LCSH):	Cellular signal transduction, Schizosaccharomyces pombe
Official Date:	February 2016
Dates:	Date Event February 2016 Submitted
Institution:	University of Warwick
Theses Department:	Systems Biology Doctoral Training Centre
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Ladds, Graham ; Chappell, M. J. (Michael J.)
Extent:	xiv, 204 leaves : charts
Language:	eng

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