Plasmodium falciparum (Pf) infected red blood cells (IRBCs) have been shown to adhere to the endothelial lining of the microvasculature as well as to uninfected red blood cells (URBCs) through variant surface antigen (VSA) known as Plasmodium falciparum erythrocyte membrane protein 1(PfEMP1) which are expressed by the var gene family. These VS As are believed to play a role in the pathogenicity of Pf during a malaria episode and are also important immune targets. This thesis focuses on the effect of culture adaptation on Pf var gene expression particularly the group A like types. Parasites were acquired from children reporting to Kilifi District Hospital (KDH) with malaria and were adapted to culture. This study did not find any association between culture adaptation and overall silencing of group A like var genes. However there was a relationship between acute stage host antibodies and group A like var expression although it wasn't significant after bonferroni correction. This thesis also used Invitrogen's Protein A Dvnabeads" to select IT04 parasite line in vitro using an adult Al immune plasma. Enrichment for PfEMPl that were well recognized by antibodies led to the selection of parasites that had elevated expression of a single var gene, ITvar51. Even though selection of field isolates with homologous plasma using the same technique was not successful, a stepwise optimisation is presented. Microarray analysis of immune selected samples revealed an overall increase in var gene expression compared to non-immune selected lines. This was supported by another finding which showed increased expression of epigenetic gene activating factors such as GCN5 histone acetyl transferase, a bromodomain and PfSET10. This study presents some evidence suggesting that antibodies regulate var gene expression using epigenetic mechanisms.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:701328 |
| Date | January 2016 |
| Creators | Shee, Faiz Mohammed |
| Publisher | Open University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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