Conference Agenda

Resistance of Plasmodium falciparum to artemisinin, the current frontline anti-malarial, greatly threatens global malaria control. Mutations in the parasites' Kelch13 (K13) protein is the major driver behind this resistance. In asexual stages, K13 forms ring at neck of parasites' cytostome, the membrane invagination responsible for haemoglobin uptake from RBC. Activation of artemisinin requires reaction with haem released from digested haemoglobin. K13 mutation is thought to cause resistance through decreasing haemoglobin uptake, causing reduced activation of artemisinin. How K13 modulates this process is undetermined. Despite continued spread of resistance in endemic regions, the role of K13 and K13 mutations on parasite transmission remain unresolved. Using an endogenously tagged version of K13, we imaged K13 throughout gametocyte development, using standard fixes as well as expansion microscopy. Similar to its asexual counterpart, K13 was found to form ring structures throughout gametocyte development, though the amount and the location of these rings varies across stages. In late-stage gametocytes, K13 also forms a hollow tubular structure, likely serving a distinct function compared to the rings. To test if K13 modulates gametocyte sensitivity to artemisinin, we have employed the Knock sideway (KS) system and KS of K13 potentially increases gametocyte survival under artemisinin treatment.