Antigenic variation in malaria: A genome-wide approach

The PfEMP1 family of proteins, which is encoded by var genes, is both a major virulence factor in P. falciparum and an important target for the host-protective antibody response. Antigenic variation of these proteins through transcriptional switches among the var genes enables the parasite to evade the immune response. Recent results have shown that the switching process is highly restricted to a single underlying pattern. In this proposal, we intend to utilise these data to identify the sequences in cis that control this pattern using a transfection approach. These sequences will then be exploited to identify the proteins that interact with them. We have also recently identified a number of novel ncRNA species in P. falciparum, some of which appear to be associated with var expression. Using a combination of informatics, microarray hybridisation, and northern blotting, we will identify most ncRNAs expressed in asexual stages and explore their role in var switching using either a knock-out or ribozyme-mediated knockdown strategy. Finally, we will use a combination of informatics and a novel method of screening peptide phage display libraries to attempt to identify the common epitopes that are expressed in either very young children or those with severe disease.

Basic Science
Genetics and Genomics

Jun 2007 — Aug 2014

$2.3M

United Kingdom