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Conference Agenda

Overview and details of the sessions of this conference. Please select a date or location to show only sessions at that day or location. Please select a single session for detailed view (with abstracts and downloads if available).

Daily Overview

Session

CP1.1: Nick White Memorial 5 min talks
Location: Lecture Theatre 1
Session Chair: Katherine Andrews, Griffith University
Session Chair: Colin Sutherland, LSHTM

Presentation 1

Using high-resolution imaging to understand how malaria parasites become resistant to frontline antimalarials

Long Huynh¹, Benjamin Liffner², Niall Geoghegan³, Sabrina Absalon², Stuart Ralph¹

1: Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia; 2: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA; 3: The Walter & Eliza Hall Institute of Medical Research, Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia

Artemisinin resistance in Plasmodium parasites, driven by mutations in the parasite's Kelch 13 (K13) protein, threatens global malaria control. K13 is important for regulating the cytostome, a double-membraned invagination used to ingest host-cell haemoglobin. This process is important because haemoglobin digestion releases haem-iron as a toxic byproduct, which is required to activate artemisinin. Mutations in K13 cause slowed-feeding and lower haem levels, allowing parasites to survive drug exposure. However, the precise mechanisms by which K13 mutations impairs parasite feeding remains unclear.
We performed a variety of high-resolution and spatial-temporal microscopy techniques to investigate cellular changes when K13 is mutated. By expansion microscopy, we confirmed K13 to localise to distinctive ring-shaped structures (~160 nm) surrounding cytostomal necks. Using a machine-learning segmentation and automated quantification pipeline, we found K13 mutant parasites produced new cytostomes at significantly slower rates than the wild-type. K13 mutants had a 4h egress delay, producing fewer total K13 rings compared to wild-type, despite maintaining normal progeny counts. Furthermore, these mutants occasionally exhibited aberrant cytostome morphologies where K13 was absent from the cytostomal neck, correlating with decreased haemoglobin uptake efficiency.

These findings fundamentally advance understanding of artemisinin resistance by providing a mechanistic explanation for K13-mediated feeding defects.