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Title: The expression of Trypanosoma brucei GPI-PLC
Author: Carnall, N.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1996
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Trypanosoma brucei, the causal agents of African sleeping sickness contains a membrane bound glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC) which exhibits exquisite specificity for GPI anchors. The enzyme is of interest as its action has the effect of releasing the variant specific surface glycoprotein (VSG) monolayer from the cell membrane in vitro, an event that is possibly analogous to a life cycle stage dependent process occurring in vivo. The regulation of expression of the GPI-PLC gene operates mainly at the post-transcription level and has been investigated through generating transgenic trypanosomes containing GPI-PLC genes with altered regulatory sequences. The results obtained suggest that the 3' (and/or possibly 5') untranslated regions (UTRs) contain elements conferring instability in procyclic forms and that the 5' or 3' UTRs contain elements that confer stability on the coding sequence in bloodstream forms. The function of the gene has been addressed by manipulation of a GPI-PLC null mutant T.brucei generated in the laboratory. The null trypanosomes contain no activity capable of cleaving the GPI anchor to release the VSG from the membrane. Despite this lack the trypanosomes can complete the life-cycle, so the GPI-PLC gene is non-essential. The GPI-PLC is not necessary for the process of antigenic variation as the null trypanosomes can establish a persistent infection in mice. However, the levels of infection (trypanosomes/ml blood) are reduced by one to two orders of magnitude. Experiments have been designed to establish whether this attenuation can be reversed by returning a wild type GPI-PLC gene to the null mutant, and with the aim of determining the phenotype of a dominant null mutation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available