Conference Agenda

Malaria remains a global health burden and with ongoing resistance across all classes of antimalarials, advancing our understanding of Plasmodium’s biology could help identify novel therapeutic targets. During continuous in vitro culture, mutations commonly arise within the parasite genome, although these are often phenotypically silent. However, we have identified a sorbitol-resistant Pf3D7 strain that no longer undergoes haemolysis when exposed to isotonic concentrations of sorbitol, indicating a disruption in nutrient acquisition via new permeability pathways (NPPs) formed by parasites to facilitate enhanced nutrient uptake. In contrast to other sorbitol-resistant lines, this occurs without growth defects under standard culture conditions. Whole genome sequencing of clonal parasites identified a recombinant CLAG3 gene (CLAG3n) with a missense mutation at the recombination region. CLAG3 is a component of the RhopH complex, a trimeric protein complex essential for NPP formation. To characterise the phenotype of our CLAG3n line, we assessed parasite growth under normal and nutrient-deprived conditions and performed osmotic lysis assays using a range of solutes to evaluate changes in substrate selectivity. Additionally, we conducted proteome-wide analyses to investigate alterations in protein expression and aim to conduct localisation studies to determine the impact of the recombination and mutation on protein export and NPP function.