Malaria parasite gene activity mapped in unprecedented detail
Friday May 28th 2021
A detailed atlas of the genetic changes malaria parasites go through as they prepare to infect people has been produced for the first time.
It maps Plasmodium falciparum in cellular detail, which the researchers hope could lead to new ways to block key stages in the parasite's development and prevent transmission.
A team at Imperial College London, UK, led by Professor Jake Baum, and the Wellcome Sanger Institute, led by Dr Mara Lawniczak, analysed the activity of genes to track how the stages were controlled and isolated the different forms of the parasite to produce 1467 transcriptomes.
Writing in the latest edition of Nature Communications, they say when the genes are turned on, they instruct the cell to make different proteins and drive developmental changes, such as causing the parasite to exit the midgut and colonise the salivary gland of the mosquito, or to travel through human cells to reach the liver, where the parasite prepares to invade more human cells.
Understanding the cellular detail of these processes work will enable researchers to develop new targets that could be blocked to stop the genetic changes and prevent transmission of the parasite.
Dr Eliana Real, from Imperial's Department of Life Sciences, said: "Being directly based on the human-infective parasite, our new data have clear implications for malaria control, which has an increasing focus on transmission blocking strategies both in terms of drugs that kill the parasite as it moves between stages and protective vaccines.
"Understanding how parasites behave transcriptionally within the mosquito vector provides a found dation from which new strategies will surely arise."
The research team also focused on the sporozoite stage, sorting parasites from within the mosquito during their development, and isolating sporozoites after an infectious bite as they interact with human skin cells.
By doing this, they found specific patterns of gene expression that define each of the critical stages in these processes.
Dr Virginia Howick, formerly of the Wellcome Sanger Institute and at the University of Glasgow, UK, said: "This fine granularity enables us to trace sporozoite developmental processes and to propose new mechanistic targets essential for each step and future vaccine targets for blocking malaria infection."
Dr Farah Dahalan, from the Department of Life Sciences at Imperial, said: "This level of gene surveillance at the individual parasite level throughout its life cycle will provide an invaluable resource for researchers to discover previously unexplored elements of Plasmodium cell biology, comparative Plasmodium species biology and the development of control methods that target particular pathways or lay the foundations for improving vaccines."
The team were compared their data with a similar set from Plasmodium berghei, which showed which genes are common between species and which are specific to the human version of the parasite.
The data are freely available on an interactive website.
Real E, Howick VA, Dahalan FA et al. A single-cell atlas of Plasmodium falciparum transmission through the mosquito. Nature Communications 27 May 2021
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