Structure-function relationship and epigenetic regulation of Plasmodium vivax tryptophan-rich antigens during host cell invasion

Plasmodium vivax endangers almost half of the world’s population and has a large socio-economic impact. Progress in battling P. vivax is slow, worsened by scarcity of vaccine candidates and drugresistant parasites. This calls for active research into P. vivax biology. Invasion of a host red blood cell (RBC) by the merozoite (MRZ) is a crucial event in the P. vivax life cycle. Yet, our understanding of interactions at the MRZ-RBC interface is limited. This project will focus on the PvTRAgs, a family of MRZ surface antigens with RBC binding capacity. While the host RBC receptors for some PvTRAgs are known, their role in RBC invasion remains to be thoroughly investigated. We therefore aim to elucidate the structure-function relationship and regulation of PvTRAgs during RBC invasion through a combination of i) molecular characterisation of PvTRAg-host receptor complexes via biophysics and structural biology, ii) screening for PvTRAg function using RBC binding assays and transgenic parasites, and iii) investigation of PvTRAg regulation at the epigenetic level through single cell omic approaches. This multidisciplinary approach is expected to establish the links between PvTRAg molecular structure, function, gene regulation and P. vivax infection. In turn, this will yield critical insights into the mechanisms underlying RBC invasion, which can be employed to support the global battle against P. vivax.