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Title: Functional genomics using an NMR-based metabolomics approach
Author: Clayson, E. M.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2006
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The aim of this study was to determine if metabolome analysis (“metabolomics”) can reveal a phenotype for S. cerevisiae strains with deleted genes that show no observable difference from wild type, with respect to growth rate on defined media. It was found that quenching cellular metabolism using ice cold water and collecting intracellular metabolites, whilst the samples were in stationary phase, gave the most reproducible profiles. Using this technique it has been shown that strains of S. cerevisiae with deleted genes in biologically distinct pathways can be distinguished. For example, strains with a gene deleted in aerobic respiration could be distinguished from profiles of strains that affect pyrimidine and proline metabolism. However a significant separation of strains whose genes affect more closely related areas of metabolism was not observed. For example proline and pyrimidine mutants could not be separated using this technique. However the technique did reveal a unique metabolite signature for one strain with a gene deletion affecting pyrimidine metabolism, which was not predicted from prior consideration of the metabolic pathway. Metabolome analysis was also applied to a more complex organism, the mouse, to determine whether genotype differences also give characteristic metabolic responses in a more complex system. Metabolite profiles from the urine of asymptomatic mice that were prone to develop Type 1 diabetes were compared with profiles in urine collected from genetically similar strains that were largely protected against the disease. The separation of animals in accordance with their genetic differences was observed. For example mouse strains which differ at only one genetic locus could be distinguished with this technique. However distinguishing strains according to their propensity to diabetes revealed a weak association.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available