Last Updated: 02/10/2025
Epidemiological and functional dissection of the co-evolution between Plasmodium falciparum parasites and sickle haemoglobin
Objectives
The main goal of this study is to uncover the functional mechanisms by which parasites evade the protective effects of HbS. An interdisciplinary team of experts from Kenya and the UK will employ epidemiological, population-genetic, multi-omic, parasite gene-editing, and parasite phenotyping approaches to address this fundamental question about host-pathogen co-evolution and human malaria resistance. The study will also contribute to the development of scientific capacity in Africa through shared leadership, student training, collaborative work, and technology transfer.
The “sickle” mutation (HbS; rs334 A>T) in the beta-globin gene (HBB) is the strongest known cause of natural resistance to Plasmodium falciparum malaria. While many mechanisms have been proposed to explain this protection, a recent paradigm-shifting study suggests that these should now be revisited. Through a large case-control study of severe malaria, the researchers discovered that parasites could escape the protective effect of HbS if they carried mutations at specific P. falciparum sickle-associated (Pfsa) genetic loci. Such mutations are common in many African parasite populations, presumably due to HbS-driven natural selection, but the mechanisms by which they allow parasites to evade the protective effects of HbS remain completely unknown.
Basic Science
Capacity Building
Enabling Technologies & Assays
Epidemiology
Genetics and Genomics
Sep 2024 — Sep 2031
$5.69M
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