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Title: Analysis of protein trafficking signals of a member of the P. falciparum 'stevor' multi-gene family
Author: Przyborski, Jude Marek
ISNI:       0000 0001 3502 5839
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2004
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Plasmodium falciparum is the causative agent of the most severe form of malaria which is responsible for 1.5-2.7 million deaths each year. The particular virulence of this species of Plasmodium is due to the ability of infected erythrocytes to cytoadhere to certain receptors on capillary endothelium, which may result in organ dysfunction or failure. The expression of a parasite derived protein, PfEMP-1 has been linked to this cytoadhesion phenotype, and to the formation of rosettes. PfEMP-1 is expressed on the surface of the infected erythrocyte, and is encoded by the var gene family. Recently, a multi-gene super family has been described consisting of the stevor (Sub Telomeric Variable Open Reading Frame) and rifin genes which, like var, are predominately sub-telomerically located. The products of the rif multi-gene family (RIFINS) have been localised to the surface of infected erythrocytes, those of stevor to membranous structures in the erythrocyte cytoplasm (Maurer's clefts). In this study we have used transfection technology to express STEVOR-GFP fusion proteins and have used these to characterise signal sequences that may be required for trafficking of STEVOR to its eventual destination. We have identified elements that are responsible for trafficking of STEVOR to the parasitophorous vacuole, the erythrocyte cytoplasm, the membrane of the parasitophorous vacuole, intra-erythrocytic membrane networks and to the Maurer's Clefts. This is the first study to dissect the trafficking of membrane proteins in P. falciparum, and further study of this unusual and complex trafficking pathway may point to novel anti-malarial strategies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral