Researchers have constructed an atlas by fine mapping the genetic changes that malaria parasites undergo during the infection lifecycle.
The transmission of the malaria parasite to and from the mosquito vector is met with a drop in parasite population numbers. The process is a highly orchestrated event that begins with parasites taking a blood meal. They then complete sexual development, fertilisation and recombination. They colonise in the midgut, developing into oocytes and finally emerging as invasive sporozoites. These sporozoites fill the mosquito salivary glands to again become transmitted to a new host during a mosquito bite. Some injected sporozoites reach the liver where they undergo a phase of population expansion, followed by a release of merozoites that enter the bloodstream.
In 2019, the estimated number of malaria deaths stood at 409,000. Children under 5 years were the most affected group. Unfortunately, mosquitos are increasingly resistant to pesticides alongside the parasite itself becoming increasingly resistant to antimalarial drugs. As a result, this has created an urgent need for novel strategies to target malaria.
The Malaria Cell Atlas
Single-cell RNA sequencing (scRNA-seq) has transformed our ability to understand complex cellular heterogeneity. Recent studies using scRNA-seq have captured fine-scale developmental transitions across the full life cycle of Plasmodium parasites. The Malaria Cell Atlas was established in 2019 as a data resource and website to provide data for researchers to explore gene expression patterns in individual parasites. However, data regarding P. falciparum – the species responsible for most human deaths and disease – has been limited to blood stages.
In this study, published in Nature Communications, researchers added a chapter to the atlas, completing a scRNA-seq survey of the transmission stages of P. falciparum. This extended from the sexual forms transmitted to the Anopheles mosquito to the invasive sporozoites delivered to the human host. The team tracked these stages by analysing the activity of genes throughout the process. Here, they produced 1,467 single-cell transcriptomes spanning the developmental transitions.
The team also compared their data with a similar set from the related parasite P. berghei, a rodent malaria parasite. They showed which genes were conserved between human and rodent parasites, and which ones were specifically relevant to humans.
The team have made the data presented in the paper freely accessible via their website. This data not only provides insights into gene function across the transmission cycle, but it also opens the door for the identification of drug and vaccine targets that may ultimately stop malaria transmission and thus prevent disease.
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