‘Malaria cell atlas’ reveals gene clusters, possible drug targets

After performing single-cell RNA sequencing on thousands of malaria parasites – the genomes of which have historically encoded many uncharacterized genes – researchers report the first high-resolution atlas of malaria parasite gene expression across the entirety of these organisms’ complex lifecycles. They call their resource the Malaria Cell Atlas. It reveals new insights into parasite gene function and regulation that should allow for the “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,” writes Elizabeth Winzeler in a related Perspective. Malaria, a serious and sometimes fatal disease for humans, is caused by single-celled organisms in the

Plasmodium

genus. These tiny parasites are unique in that their complex lifecycle carries them through a variety of morphological stages, allowing them to live in cellular environments across both vertebrate and invertebrate hosts. Although malaria is one of the leading infectious diseases worldwide – responsible for nearly a half-million human deaths and hundreds of millions of infections annually – the parasites remain largely uncharacterized at the molecular level. Virginia Howick and colleagues profiled the single-cell transcriptomes of 1,787 individual

Plasmodium berghei

– the rodent model of malaria parasite – across all life-stages, spanning vector mosquito to mammalian host. Howick et al. discovered groups of genes whose function was conserved across lifecycle stages, indicating potential targets for future treatments. Using droplet-sequencing, the researchers further sequenced more than 15,000 additional cells across three different

Plasmodium

species, including those isolated directly from infected human patients. In doing so, they were able to characterize and align the developmental stages across these species, giving them a view into both differences and similarities in gene expression among them.

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