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Title: Analyses of Plasmodium falciparum var genes
Author: Ward, C. P.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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Plasmodium falciparum var genes encode the PfEMP1 family of variant antigens expressed on the surface of infected erythrocytes. PfEMP1 mediates the adhesion of the parasitized erythrocyte to the venular endothelium and to uninfected erythrocytes. PfEMP1 variants use a range of different host molecules as receptors in these adhesive interactions. The expression of different PfEMP1 variants may directly affect the clinical course of malaria infection by defining the distribution and intensity of parasite adhesion in the microvasculature of various organs within the host. PfEMP1 is a major focus of the host immune response, and the slow onset of clinical immunity in endemic areas may be explained by the gradual accumulation of effective responses to a wide range of PfEMP1 variants present in the local parasite population. It has been hypothesised that the immune response to PfEMP1 may act to stratify the parasite population into co-circulating 'strains' defined by discrete, non-overlapping repertoires of var genes. Here, the DBL1 region of 56 var gene variants from 6 genetically distinct co-circulating Sudanese parasites have been cloned and sequenced. Sequence comparisons suggest that recombination and gene duplication are important mechanisms in the generation of new var variants. A model of the basic structural framework of DBL1 sequences is described and "sequence subtypes" identified within variable regions of sequence. Phylogenetic analysis of the Sudanese and other var sequences from GenBank fail to support the 'strain' model for Sudanese P. falciparum and suggests that the global pool of var genes is finite. 40 Sudanese variants have been expressed as GST-fusion proteins with yields of varying quantity and degree of degradation. 10 of the recombinant proteins have been tested against a cohort of sera in a pilot ELISA, and the role of anti-PfEMP1 immune responses in the development of clinical immunity is discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available