PAMGEN: Genetic interactions between human populations and malaria parasites in different environmental settings across Africa

Principal Investigator

Scientific Description:

Our overarching goal is to build a team of African scientists that can harness advanced genomic and computational technologies to better understand how variation in human, parasite and mosquito genomes, as well as in the ecological environment, impact on malaria at individuals and population level. We will assess human genomic variation along a malaria transmission gradient in seven African endemic countries. This will combine archived and prospective samples with existing genomic data to characterise and map variation in red blood cell (RBC) surface receptors. The project will determine if variance in these receptors is associated with genetic diversity and selection of ligands, and subpopulations of parasites across transmission zones. The association between these interactions, disease outcomes and interventions will be further investigated.

As the parasite also interacts with the mosquito vector, we will assess the association between Anopheles and parasite genetic variation across sites. Genetic and genomic data generated at the Wellcome Trust Sanger Institute and at the MRC Unit The Gambia will be shared across the network and with the DELGEME and WACCBIP-DELTAS programmes for student training and research purposes. Over the project lifetime the data will be used to identify genetic markers of direct relevance to malaria elimination.

Lay Description:

For thousands of years, humans have continuously adapted to resist malaria parasites. In turn, malaria parasites have evolved to evade our immune system and antimalarial drugs. Understanding this deadly evolutionary struggle is crucial to maintain the efficacy of antimalarial drugs, discover new treatments, and develop effective vaccines. Pan-African Malaria Genetic Epidemiology Network (PAMGEN) is a team of African scientists studying how genetic changes in humans and malaria parasites impact on the disease in individuals and communities in different ecological environments. In order to infect humans, malaria parasites need to invade our red blood cells. PAMGEN will examine differences in humans and parasites DNA within populations of seven African countries (Gambia, Ghana, Mali, Cameroon, Kenya, Ethiopia and Madagascar). This work involves studying specific parasite genes and receptors on the surface of human red blood cells that malaria parasites exploit during invasion. The network will also investigate potential relationships between genetic differences in all malaria genomes – human, parasite, and mosquito. Initially, PAMGEN will focus on generating high-quality data that will be shared within the network and the wider scientific community. Ultimately, these data resources will power research that generates information to support malaria elimination efforts.

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