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Title: Studies of cytoadherence and var gene transcription in Plasmodium falciparum
Author: Clottey, George Thomas
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2009
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Plasmodium falciparum infection can be distinguished from that of other plasmodia which infect humans by one specific facet of its biology, that of sequestration of mature developmental forms in capillary beds. A variant antigen, Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP-1) is involved in this process and members of this trypsin soluble 210-230 kDa protein family are responsible for cytoadherence of mature infected erythrocytes. A model system has been developed to investigate the molecular basis of infected erythrocyte adhesion to host endothelial receptors. P. falciparum clone 3D7A was selected for adhesion to Chinese Hamster Ovary (CHO) cells resulting in an adhesive phenotype, which is sensitive to trypsin treatment of infected erythrocytes. The nature of the cytoadhesion receptor on the CHO cell surface has been analysed and does not appear to correspond to any of the protein or glycoprotein cytoadherence receptors so far described. It has been demonstrated that unselected 3D7A transcribes at least 27 different var genes. On selection for adhesion to CHO cells this transcription is narrowed down to the transcription of a single gene named var-CHO. This gene has been cloned, sequenced and annotated. Var-CHO consists of 3 DBL domains, DBL-x, DBL-b and DBL- s, two CIDR domains, CIDR-x and CIDR-b, and a C2 domain. A provisional genomic map position of this member of the PfEMP-1 has been identified as chromosome 13 by a combination of pulse field gel and P. falciparum genome project data.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available