Malaria Cell Atlas created by Wellcome Sanger Institute to help tackle global health challenge
A Malaria Cell Atlas has been created by the Wellcome Sanger Institute and its collaborators to help the research community develop drugs and vaccines against a disease that claims the life of nearly 450,000 people a year.
It is the first detailed map of the behaviour of individual malaria parasites across their complex life cycle, and illustrates how parasites change as they develop in both the mosquito and the human host.
They achieved it using advanced single cell RNA sequencing techniques to isolate individual parasites and measure their gene activity.
The findings were published in the journal Science.
Dr Virginia Howick, joint first author from the Wellcome Sanger Institute, said: “We’ve created an atlas of gene activity that spans the complete life cycle of the malaria parasite. This is the first atlas of its kind for a single-cell organism. The malaria parasite’s life cycle is key to research into this disease and the Malaria Cell Atlas will help us truly understand the parasite in order to effectively control malaria.”
More than 200 million people worldwide are affected by malaria. Nearly 450,000 people died from it in 2017, and the majority of those were children under five, according to the World Health Organization.
The disease is caused by the Plasmodium parasite that spreads to humans through the bites of infected mosquitoes.
A major global health challenge is presented by the malaria parasite’s ability to become resistant to multiple frontline drugs.
There have been advances in vaccine development, but the fact that the function of 40 per cent of the parasite’s genes were unknown has been a significant barrier to developing new drugs.
The Malaria Cell Atlas - a resource freely available to the research community - gives the highest resolution view of malaria parasite gene expression to date.
The team isolated and measured the gene activity of 1,787 individual malaria parasites from 10 stages across their complete life cycle, in both humans and the mosquito.
Researchers gave mosquitoes infected with malaria a fake blood meal to capture the parasites they released in their spit, for example, enabling them to compare them to parasites that remained in the salivary glands.
The team measured which genes were active in individual parasites across the entire life cycle.
Knowing which genes are key to each stage of the parasite’s life cycle is important in identifying weak spots that could be of use in creating new drugs.
The researchers looked at the activity of previously studied genes that showed similar patterns of activity to the genes with unknown function to work out what they did.
Andrew Russell, joint first author and a PhD student at the Wellcome Sanger Institute, said: “Using the Malaria Cell Atlas, we’ve inferred the roles of parasite genes that until now were entirely unknown.
“We do this through ‘guilt-by-association’: by looking at functions of previously studied genes, we can predict roles of unknown genes if they show similar activity patterns to known genes. This provides a new opportunity to find novel drug targets.”
Another single-cell technology was used to examine a further 16,000 individual parasites from the blood stages of malaria that infect mice, monkeys and humans.
Despite the hosts being so different, the gene activity behaviour across the three malaria parasite species was similar.
This could be a critical discovery, as identifying genes essential in multiple species of malaria could help identify drug targets that could be effective in all five types of the disease that infect humans.
Parasites in the blood of three Kenyan people being treated for malaria were also collected.
The team used the Malaria Cell Atlas as a reference to examine individual “wild” parasites from two different human malaria parasite species for the first time.
This process can be used to understand which genes are active in natural, real-world infections, compared to those in parasites cultured in the laboratory.
Dr Mara Lawniczak, lead author from the Wellcome Sanger Institute, said: “To defeat malaria we need to understand all the tricks the parasite uses throughout its life cycle.
“The Malaria Cell Atlas is the first detailed map that gives us insight into how different one parasite is from another, even when they are genetically identical.
“We face the problem of malaria becoming more resistant to current malaria drugs, and as new drugs are introduced, we hope the Malaria Cell Atlas will act as a reference to understand how parasites change their behaviours in response to our efforts to control them. Knowing this will help reveal how to corner the parasites and ultimately eliminate them.”
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