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Title: Analysis of CTRP, a Plasmodium ookinete surface protein
Author: Ramakrishnan, Chandra
ISNI:       0000 0004 2748 2572
Awarding Body: University of London
Current Institution: Imperial College London
Date of Award: 2007
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The Plasmodium surface protein CTRP mediates ookinete motility, adhesion to the mosquito midgut and the basal lamina and invasion. It is part of the TRAP protein family members of which play similar roles in other stages of Plasmodium and in all apicomplexan species examined to date. Uniquely, CTRP contains multiple copies ofvon Willebrand factor A-related (A) domains and thrombospondin type 1 repeat-like (TS) domains. CTRPko ookinetes are non-motile, cannot adhere to the midgut and do not develop into oocysts demonstrating that CTRP is essential. To understand the roles of A and TS domains, endogenous CTRP was replaced with mutants lacking either all the A domains or all the TS domains. The impact of domain deletions on oocyst number was studied. Ookinetes carrying mutant CTRP lacking TS domains produced similar numbers of oocysts to wildtype, whereas CTRP lacking A domains did not produce oocysts. Thus the A domains are essential for the formation of oocysts, whereas TS domains are non-essential. . 3sS-methionine labelled ookinetes were used for co-immunoprecipitation with CTRP to identify binding partners of CTRP. Three putative interaction partners of 110, 100 and 60 kDa molecular weight were isolated. Further work is needed to obtain these co- precipitates in sufficient amounts for unequivocal characterisation by mass spectrometry. To evaluate CTRP as a transmission-blocking vaccine target, antibodies were raised against the third TS domain of CTRP. They recognised CTRP in Western blots and immunofluorescence assays. In transmission-blocking assays however, they failed to reduce transmission. The TS domains of CTRP are clearly not an appropriate target for transmission-blocking vaccines, however further work is required to determine whether A domains can be targeted effectively. Future studies on CTRP and related proteins may elucidate the structural and essential functional requirements of proteins involved in invasion, and provide new ration ales for vaccine and possibly drug design.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available