Investigation of the Plasmodium vivax reticulocyte invasion process : a combination of wet and dry lab approaches

Malaria is among the most impactful infectious diseases globally, and is caused by parasites of the genus Plasmodium. Plasmodium vivax is the second most important cause of human malaria, mainly affecting non-African countries. Despite the global health impact of P. vivax, our understanding of its unique biology is severely limited due to the lack of a culturing system. One of the processes that we do not fully understand is how the parasite enters the red blood cells. P. vivax has a specific preference for reticulocytes, the young fraction of red blood cells. Through recognition of multiple red blood cell surface proteins (receptors) by parasite proteins (ligands), invasion can be accomplished. These receptor-ligand interactions are interesting targets for drug and vaccine development, and this thesis aimed to investigate new invasion interactions. To overcome the absence of a culture system, we combined several lab and bioinformatics approaches. This enabled us to identify a new invasion receptor, called band 3, which most likely is recognised by ligands from the PvTRAg gene family. In addition, we placed a particular focus on sequencing of genetic material as a new avenue to study the invasion process. To simplify future Plasmodium sequencing studies, a new reference genome for South American P. vivax isolates was developed, and we successfully applied Nanopore adaptive sampling to enrich Plasmodium DNA during sequencing, this way simplifying the sequencing protocol.