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

疟疾是由一种寄生虫引起的，这种寄生虫只由蚊子传播。最大的减少和根除疟疾的成功案例是通过阻断传播实现的。从历史上看，这是通过控制蚊子来实现的。以通过蚊子传播的寄生在人类宿主中的少数专门寄生虫为目标将提供同样有效的疟疾控制方法，但我们对这一群体知之甚少。到目前为止，寄生虫表达的基因已经通过将数百万种寄生虫组合在一起进行了分析。这种方法混淆了个体寄生虫之间的差异，这些差异可能是成功进入另一个宿主或抵抗我们用来杀死寄生虫的药物的基础。我们最近开发了一种方法，一次分析一种寄生虫。这一技术飞跃使我们能够在实验室中比以往任何时候都更精确地了解寄生虫，重要的是了解在寄生虫的整个生命过程中，无论是在宿主还是在蚊子中，一种寄生虫可能与另一种寄生虫有何不同。虽然实验室环境和寄生虫的实验室菌株是了解寄生虫生物学的强大工具，但在实验室里，我们无法了解存在于野外的寄生虫的全部多样性，这些寄生虫会给受感染的个人造成毁灭性的后果。在这个项目中，我们建议与马里科学家合作，在个体水平上描述野生寄生虫的特征。我们的探索将使我们能够首次在单一寄生虫水平上描述撒哈拉以南非洲三种主要疟疾寄生虫的特征。我们将把这些数据整合到一个叫做疟疾细胞地图集的互动网站中。这将成为研究界的关键资源。然后，我们将探索从一个患者到另一个最致命的疟疾物种在两个患有疟疾症状的患者和没有患有疟疾的受感染携带者中的变化，这两者都有助于整个寄生虫的储存。总而言之，我们将观察30多万种寄生虫，并对每种寄生虫之间的相似和不同有非常深刻的理解。了解这种传染性宿主对于确定寄生虫如何有效地从一个人传播到另一个人是关键的。总之，我们使用尖端工具探索野生寄生虫的发现将是了解疟疾和如何最好地控制它的关键。

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.