Active Genetics & Molecular Biology Plants, Animals & Ecology

Recovering Evolutionary Drivers of MAlarial Parasites - leveraging genomics past and present

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AI plain-English summary

Malaria parasites preserved in ancient human and animal remains are being extracted for their DNA to track how the disease evolved and spread over thousands of years. This matters because global progress against malaria has stalled. Insecticide-resistant mosquitoes, drug-resistant parasites, and the constant threat of animal-borne infections are undermining eradication efforts. Current surveillance focuses almost entirely on modern human cases, ignoring the non-human hosts and historical transmission patterns that shape parasite evolution. Without knowing where major malaria species originated or how they adapted to different hosts and drugs, researchers are working blind. RED-MAP will recover genetic material from a curated collection of parasites spanning millennia, from both human and non-human primate samples. By combining ancient genomics, population genomics, and computational biology, the project will pinpoint the spatio-temporal origins of major malaria agents and track the genetic drivers of antigenic variation, host adaptation, and drug resistance. If successful, this fundamental science will provide a radical new perspective on an age-old disease. The methods and insights could also be portable to tackling other infectious diseases, though no immediate practical application is promised. Similar fundamental research into pathogen evolution has historically underpinned vaccine development and outbreak forecasting.

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Malaria has had a devastating impact on human health through history and currently inflicts over 600,000 deaths annually. Global progress against malaria has levelled off, compounded by pandemic-related disruptions reducing access to antimalarial drugs and preventive vector control measures. Increasing levels of insecticide resistance, antimalarial drug resistance in parasite populations and the perennial risk of zoonoses continue to challenge eradication efforts. Malaria is caused by several species of Plasmodium, protozoal parasites which infect an array of hosts. Endemicity, at least for human-associated parasites, is increasingly well characterised; mostly confined to tropical and sub-tropical latitudes. However, malaria was once a truly global disease, with the last indigenous cases in Europe persisting until the 1970s. Molecular surveillance has revised the number of parasite species able to infect humans, though evolutionary studies of Plasmodium continue to mostly neglect the nonhuman pathosystem. The lack of quantitative assessment of past transmissions and reservoir hosts poses a major hurdle to identifying the forces shaping parasite evolution both now and in the future. RED-MAP will define the genetic and ecological drivers of malarial parasites using an innovative combination of ancient genomics, population genomics and computational biology. Employing state-of-the-art techniques, I will recover DNA from a curated collection of parasites, stretching back over thousands of years, from human and non-human primate samples. Leveraging this unprecedented resource, I will pinpoint the spatio-temporal origins of major malarial agents and track determinants relevant to parasite success including antigenic variation, adaptation to distinct hosts and the ability to resist antimalarial treatment. I will provide a radical new perspective on the age-old challenge of malaria and deliver frontier research portable to tackling other infectious diseases.

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Researchers

Lucy Van Dorp (Principal Investigator)

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Research Grant

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