Incorporating complex genetic and antigenic variation into host-parasite association studies

Malaria parasites carry large, repetitive chunks of DNA that standard genetic scans routinely miss. Most studies of how human genetics and parasite genetics interact to determine disease severity have ignored these complex variants because they are difficult to sequence and analyse. A recent landmark study found a strong link between the sickle-cell trait and three specific parasite genes, but it deliberately excluded the messy, repetitive regions near the ends of parasite chromosomes. This PhD project will use long-read sequencing—which reads much longer stretches of DNA in one go—to capture those hidden regions from natural infections in The Gambia and Kenya. The team will then apply pangenomic methods to systematically catalogue this complex variation and test whether it influences how sick a person gets. If successful, the work will reveal whether these overlooked genetic elements play a role in malaria outcomes, potentially identifying new targets for drugs or vaccines. This is fundamental science: it aims to map the full genetic landscape of the parasite, not to produce an immediate clinical tool. Similar mapping efforts for other pathogens have later informed vaccine design and drug resistance surveillance.