Using single-cell RNAseq to investigate human malaria parasite transmission dynamics

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Malaria is caused by a parasite that is transmitted exclusively by mosquitoes. The greatest malaria reduction and eradication success stories have been achieved by interrupting transmission. Historically, this has been through mosquito control. Targeting the small population of specialised parasites residing in the human host that are transmitted through mosquitoes would provide a similarly powerful malaria control method but we know too little about this population. Until now, the genes expressed by parasites have been analyzed by combining millions of parasites together. This approach confounds differences between individual parasites that could underlie success in getting into another host or in resisting the drugs we use to kill the parasites. We have recently developed a method to analyse single parasites one at a time. This technological leap has allowed us to understand parasites in the laboratory with more precision than ever before and importantly to understand how one parasite may differ from another during the whole life of the parasite both in the host and in the mosquito. Although the laboratory setting and lab strains of parasites are powerful tools for understanding parasite biology, in the lab we cannot understand the full diversity of parasites that exist in the wild causing devastating consequences for infected individuals. In this project we propose to characterise wild parasites at an individual level in partnership with Malian scientists. Our exploration will allow us to characterise the three main species of malaria parasite in sub-saharan Africa on a single parasite level for the first time. We will integrate the data into an interactive website called the Malaria Cell Atlas. This will become a key resource for the research community. We will then explore the changes from one patient to the other of the deadliest malaria species in both patients that are suffering from malaria symptoms and also from infected carriers who are not suffering from malaria, both of which contribute to the overall reservoir of parasites. Altogether, we will look at more than 300,000 individual parasites and get a very deep understanding of how individual parasites are both similar and different from each other. Understanding this infectious reservoir is pivotal to identifying how parasites efficiently get from one person to the next. Altogether our findings using cutting-edge tools to explore wild parasites will be key to understanding malaria and how to best control it.