Plasmodium falciparum is responsible for most of the fatalities caused by human malaria infection. The severe pathology is highly associated with trafficking of virulence complex proteins to the cell surface. The virulence complex plays crucial roles in antigenic variation and cytoadhesion of infected cells in the microvasculature of vital organs. Trafficking of virulence complex proteins to the host cell surface is dependent on parasite-derived membranous structures, named Maurer’s clefts (MCs). To date, the underlying mechanism of how MCs aid in the establishing the virulence complex is not well understood. Besides, the genesis and proper function of these compartments heavily relies on a range of proteins and potentially lipids residing in MCs, but the underlying mechanisms remain elusive.
To unearth the genesis and function of these organelles, we characterised PFE60, a MCs resident protein that is part of the virulence complex. We determined its role in the biogenesis of MCs and how it is involved in trafficking of other parasite exported proteins. Based on these phenotypic analyses we propose a model on the function of this protein and how it interacts with other proteins in the MCs. Furthermore, we investigated contributions of lipids (in particular raft lipids) in MCs function and their biogenesis pathway. To do this we advanced existing lipid imaging techniques and established molecular lipid binding probes that are specific to raft lipids sphingomyelin and cholesterol. These probes can be used to detect lipids in live or fixed cells using fluorescence or electron microscopies.