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Title: Genome-wide studies of cellular aging in fission yeast
Author: Smith, G. C.
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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Research conducted using simple organisms such as yeasts and worms have contributed greatly to our understanding of the molecular basis of ageing. Here we used the fission yeast, Schizosaccharomyces pombe, as a model organism to study the regulation of chronological lifespan (CLS) in response to glucose depletion. A long-lived mutant, pka1 deletion mutant (pka1∆), and a control strain were induced into a non-proliferating state via glucose depletion allowing us to map the transcriptome, proteome, and free amino acid pool during CLS. The transcriptome was analyzed to identify any ageing-related changes in differential expression (including amongst annotated canonical ncRNAs and recently classified lncRNAs) and for any alterations in splicing patterns. The proteome and transcriptome showed weak positive correlation at initiation of CLS in both the pka1∆ and wild type with an age related decline observed. By integrating GO term annotations with our results we found that the correlation between protein and mRNA levels is related to the gene function. A sub-population of hyper-stable mRNAs showed inversely correlated expression during CLS, high fold increases in the mRNA were reflected by high fold decreases in the proteome. The role of RNA Binding Proteins (RBPs) in decoupling of the proteome from the transcriptome during CLS was investigated with correlations hinting at their possible role in age-related post-transcriptional regulation. A loss of stoichiometry in protein complexes was observed across CLS. Deregulation of free amino acid pool in the wild type and to some extent the pka1∆ was observed with both showing a marked decline in glutamate and the long-lived mutant showing an accumulation of aspartate. Several bioinformatics tools developed during the project were also described.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available