Interrogating host-parasite interactomes with multiscale proteomics

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Malaria is an acute disease caused by the parasite Plasmodium Falciparum, which is directly responsible for hundreds of thousands of deaths per year. Plasmodium Falciparum enters the human bloodstream when an infected mosquito penetrates the skin. The parasite then penetrates red blood cells and makes its home inside them. Here, it can hide from the human immune system whilst creating a place for it to survive. This process is often referred to as remodeling. The parasite's remarkable ability to evade the human immune system is what makes it so challenging to eradicate or design new therapeutics against it.Despite its clear importance the details of how Plasmodium Falciparum remodels the red blood cell is still unclear how it does this. We already know that the parasite uses some of the red blood cells' own proteins to carry out the necessary functions but do not have a precise understanding of which ones. It is important to understand which proteins the parasite is using so we can design drugs to stop it in its tracks.Firstly, this research will generate a "map" of interactions between the parasite and the host human cells whilst the parasite is remodeling the red blood cells for its purposes. Secondly, key interactions need to be understood in more detail and we will use other methods to see how human proteins change shape when they are used by the parasite. This will give us key insights into how they function. Finally, we will develop a new method that will allow us to examine how these interactions are changing inside the red blood cells. Together these data will provide us a new understanding of the remodeling process. In particular, it will inform medicinal chemists how to design new drugs against the malaria parasite.