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Title: The regulation of gene expression in mycobacterium tuberculosis
Author: Frota, Cristiane Cunha
ISNI:       0000 0001 3484 8323
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 2002
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Mycobacterium tuberculosis is a major human pathogen. The complete genome sequence of M. tuberculosis has recently been published. The broad aim of this project was to use post-genomic approaches to study aspects of the basic biology of M. tuberculosis. The specific aims of the project were: To compare the human pathogen, M. tuberculosis with the murine pathogen Mycobacterium microti. To investigate the role of a family of transcriptional regulators by creating mutants of these genes in M. tuberculosis. To characterise the in vivo and in vitro phenotypes of the mutants. The comparison of M. microti and M. tuberculosis initially involved the use of DNA microarrays to investigate genome structure. This revealed several deletions in M. microti, some of which corresponded to deletions in the vaccine strain M. bovis BCG. The effects of genomic differences on gene expression were also compared using the microarrays, and also using proteomics. Two members of the AraC/XylS family of transcriptional regulators were among the many genes found to be differentially expressed between the two species. A search of the M. tuberculosis genome identified five members of this gene family. Attempts to generate deletion mutants of each of these five genes were made, and resulted in mutants of four of them (Rv1395, Rv1931c, virS [Rv3082c] and Rv3736); we were unsuccessful in deleting the fifth gene (Rv3833). The four mutants were compared to their parental strain in a mouse model of infection. One mutant (Rv1931c) showed evidence of reduced virulence. This mutant was investigated further, to identify which genes might be regulated by the product of Rv1931c. It was possible to identify a number of genes involved in (i) the transition from exponential to stationary phase, (ii) oxidative stress and (iii) acidic stress, which are candidates for genes under the regulation of Rv1931c.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available