Functional investigation of Plasmodium falciparum var genes expressed at high levels in the tissue of Malawian paediatric malaria patients

An integrated approach to malaria control is essential, and the application of genomics is one area that can provide biological insights into important evolutionary forces in P. falciparum. An improved understanding of the parasite’s genetic diversity, population structure, and natural selection will have practical implications for developing methods of disease control. In particular, genetic variation enables the parasite to overcome host immunity, antimalarial drugs, and vaccines to establish persistent infections and increase transmission.

Building on this, my current work suggests that only a limited subset of var/PfEMP1 variants may drive key pathological outcomes in severe malaria. The aim is to investigate their tissue-specific localisation, determine whether particular PfEMP1 types are associated with clinical diagnoses such as cerebral malaria, and characterise the adhesive domains that define each variant. By combining expression profiling with binding assays using relevant endothelial receptors and by analysing tissue samples from a larger number of patients, this work will clarify how specific PfEMP1 subtypes contribute to disease presentation and sequestration patterns.

Feb 2007 — Feb 2012

$929,649

Malawi
United Kingdom