Join our last online ASP Seminar Series for this year on Friday 20th November 2026 @1pm AEDT, featuring Josh Levendis, University of Melbourne presenting “The RNA modification m6A positions polyadenylation in Plasmodium falciparum” and Alex Harris, Burnet Institute presenting “Repeated malaria vaccine booster doses in children shapes protective antibody responses” with co-chairs Karan Singh and Kaitlin Turland, Adelaide University.
Please register online using this link for your unique passcode to join the seminar. After registering, you will receive a confirmation email containing information about joining the meeting.
Josh is a 2nd year PhD student at Bio21, The University of Melbourne. He is a member of the Ralph lab, where he completed an undergraduate project and Honours. Before studying molecular biology, he worked as an embedded software engineer making broadcast equipment and data storage. Now, he’s interested in changing RNA modification programs in vivo and using long read sequencing to understand parasite development. He recently obtained a chess.com rating of 1600 which he is pretty chuffed about.
Talk Title: The RNA modification m6A positions polyadenylation in Plasmodium falciparum.
Abstract: N6-methyladenosine (m6A) is the most abundant modification in eukaryotic mRNA and can influence gene expression, but the molecular mechanisms by which it does this at an individual gene level are poorly understood. The eukaryote with the highest known percentage of adenosine in its RNA is Plasmodium falciparum, causative agent of the deadliest form of malaria. P. falciparum has a high genomic AT content (>80% A+T) and a particular A-bias in mRNA – coding strands have an average adenosine content of 44%. Plasmodium parasites employ extensive transcriptional and post-transcriptional control over gene expression to differentiate within and between sexual and asexual stages in response to changing environments and hosts.
We used Nanopore direct RNA sequencing and GLORI-seq to interrogate m6A methylation of the asexual P. falciparum transcriptome, revealing m6A depletion in protein coding regions relative to the 3’UTR, where m6A is deposited in precise patterns approximately 50 nt upstream of the polyadenylation site. We used an inducible protein mislocalisation system to disrupt the methyltransferase, which writes m6A to mRNA, and observed m6A depletion associated with transcriptional readthrough and chimeric transcripts. We show that m6A in transcript 3’UTRs is required for faithful positioning of polyadenylation and transcription termination.
Asexual P. falciparum parasites can differentiate into sexual stage gametocytes. Upon mosquito uptake, gametocytes mature into gametes due to a decrease in temperature and extracellular acidity. These parasites have stage and sex specific gene expression, and we observed a handful of sex-specific genes whose transcripts are consistently methylated in either their exons or retained introns, resulting in early transcription termination. This work highlights the importance of m6A to mRNA processing in P. falciparum, and potentially a wider role in post-transcriptional regulation.
Alex Harris is a third-year PhD candidate in the ‘Malaria Immunity and Vaccines group’ at the Burnet Institute, supervised by Liriye Kurtovic, Adam Thomas, and James Beeson. His work focuses on better understanding the immune response induced by the RTS,S malaria vaccine in children. His research investigates Fc dependent functional antibody responses induced following RTS,S vaccination in children and their associated cellular effector functions. By understanding the determinants of optimal immunity to malaria, he aims to inform optimal vaccine policy and the development of next‐generation vaccines. Alex completed his Bachelor of Science at Monash University, majoring in immunology and physiology, in 2021. In 2022, he completed an honours research project at Burnet Institute, then worked as a research assistant, before starting his PhD in 2024.
Talk Title: Repeated malaria vaccine booster doses in children shapes protective antibody responses
Abstract: Effective malaria interventions are essential to reduce disease burden in children. Combining RTS,S vaccination with seasonal antimalarial chemoprevention was shown to enhance efficacy against clinical malaria among children by ~72% over the first year compared to either intervention alone. However, over four years, efficacy of this combination steadily decreased despite annual boosters. Protective antibodies were shown to peak following primary vaccination but became progressively lower with each annual booster. It is unknown what drives poor antibody responses to boosters, which likely vary between different antibody isotypes and antigenic targets, and if host factors such as viral co-infections and micronutrient deficiencies are implicated in this suboptimal response.
To address these knowledge gaps, we evaluated plasma samples from young children (n=1,929) in West Africa who received RTS,S and subsequent boosters with or without seasonal chemoprevention over four years as part of a phase-III clinical trial. We found that repeated vaccine doses had differential effects on antibody responses, which varied by the antigenic region of the vaccine. We also investigated the impact of host factors on these responses. By improving our understanding of the immune response to repeated booster doses, this work informs optimal RTS,S implementation strategies to improve vaccine efficacy and longevity.
Our ASP Online Seminar Series image is created by Thorey Jonsdottir.
