Authors: Johanna Todd, Future Science Group
Virginia M Howick (Wellcome Sanger Institute, Cambridge, UK) and her team have performed single-cell RNA sequencing on thousands of malaria parasites, creating a transcriptional atlas of the Plasmodium berghei lifecycle, termed the Malaria Cell Atlas.
To start to build the Malaria Cell Atlas the transcriptomes of 1787 individual Plasmodium berghei were obtained across the ten stages of the lifecycle, from the vector mosquito to mammalian host in the rodent model of the parasite. This could provide possible drug targets and future treatment options for malaria. In addition by looking at the activity of previously studied genes the team could infer potential functions for currently unknown genes.
Andrew Russell, joint first author and a PhD student at the Wellcome Sanger Institute, commented: “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.”
The researchers expanded the Atlas by sequencing a further 15,000 additional cells from three different malaria parasite species, discovering gene clusters whose function was maintained throughout all stages of life.
Finally, the team collected samples of the parasite from three infected individuals from Kenya. Using the Malaria Cell Atlas as a reference they were able to examine individual ‘wild’ parasites for the first time, opening the door to learning about gene function in natural infections and whether these might differ from lab models.
Mara Lawniczak (Wellcome Sanger Institute) explained: “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.”
This is the first high-resolution transcriptional atlas of the entire Plasmodium berghei lifecycle, enabling a global view of gene expression and allowing functional predictions based on co-expression. Elizabeth Winzeler writes in a perspective that the Malaria Cell Atlas allows for “better prioritization of genes for those seeking to develop drugs, vaccines, [and]diagnostics or for those who seek to understand the spread of drug resistance.”
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Sources: Howick VM, Russell AJC, Andrews T et al. The Malaria Cell Atlas: Single parasite transcriptomes across the complete Plasmodium life cycle. Science 365(6455), eaaw2619 (2019); www.eurekalert.org/emb_releases/2019-08/aaft-ca081919.php