Guerreiro, Tailise Carolina de Souza (2019) Gene expression stochasticity, protein synthesis and the ageing process in the budding yeast Saccharomyces cerevisiae. PhD thesis, University of Warwick.

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Abstract

Analysis of the biological processes that influence ageing is crucial to developing a full understanding of the mechanisms underpinning it. Saccharomyces cerevisiae has been shown to be a key model for ageing research since the pathways for the ageing process are highly conserved between eukaryotes, from yeast to man. Previous reports have demonstrated the role of translational control in life span modulation. Calorie restriction increases life span by a mechanism mediated by Target of Rapamycin (TOR) signalling, which in turn reduces synthesis and activity of ribosome subunits as well as global translation activity. Consistently, a system-level transcriptome and proteome analysis demonstrated that, as the cells age, the proteome increasingly uncouples from the transcriptome, with this protein overrepresentation being linked to ageing. In this study, we have applied an innovative approach combining cell wall staining, flow cytometry and microfluidics, to investigate at a single-cell level whether the noise characteristics of yeast cells change with increasing age and to what extent individual components of the translation machinery contribute to the relationship between ageing and noise. We find that gene expression noise generally increases as cells age, but that deletion of eIF4G1 (translation initiation factor 4G1) both restricts age-dependent increases in noise and extends life span, thus indicating that translation machinery activity and gene expression noise are inversely related to replicative lifespan.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QH Natural history Q Science > QK Botany
Library of Congress Subject Headings (LCSH):	Aging, Gene expression, Proteins -- Synthesis, Saccharomyces cerevisiae
Official Date:	April 2019
Dates:	Date Event April 2019 Submitted
Institution:	University of Warwick
Theses Department:	School of Life Sciences
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	McCarthy, John E. G.
Sponsors:	CAPES (Organization : Brazil)
Extent:	xxi, 149 leaves : illustrations, charts
Language:	eng

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