Written by Alessia Hysa, PhD candidate at the Burnet Institute and University of Melbourne, Australia.

From 20th to 22nd May 2025, Plasmodium and Toxoplasma experts gathered from around the world in the idyllic city of Heidelberg to discuss the latest advancements in the biology and pathology of the malaria parasite. Across several sessions, lunches, and dinners, we were brought together by a shared passion and commitment to the persistent fight against malaria.

Session 1: epidemiology

The conference opened with Abdoulaye Djimdé with an impactful presentation highlighting the importance of translating our research into policy that can be implemented in the field. Fieldwork on Plasmodium genomics led by his laboratory in Mali, suggests that we can no longer adopt a ‘one-size-fits-all’ strategy to combat malaria. Furthermore, they have been working closely with policymakers, showing them a glimpse into a day in the life of a scientist and engaging with those who will implement our findings. Azza Idris presented an overview of the evolution and mechanisms of action of CIS43 and L9, the promising circumsporozoite protein monoclonal antibodies. Martha Kivecu used MalariaGEN Pf7 as a tool to delve deep into the origin, history, and genetic diversity of Plasmodium. Gustavo da Silva investigated the levels of Plasmodium vivax transmission facilitated by local and imported parasites within Ethiopian villages and compared the genetic relatedness of asymptomatic and clinical cases. Kevin Tetteh discussed the challenges of successfully translating research into diagnostics and how we can circumvent this by (1) identifying the public health need for the diagnostic and (2) convincing policymakers by demonstrating the impact of the diagnostic in averting DALYs. Annie Forster investigated the biological functions of Pfsa loci that contribute to parasite sickle resistance. Mathieu Quenu compared var gene expression in the dry versus wet season and defined its contribution to chronic and asymptomatic P. falciparum infections.

Session 2: vaccines and immunity

Maria Mota opened the session with important insights into the Plasmodium liver stage: (1) proliferation rate differs between different hepatocytes, (2) this stage is not silent and has an impact on disease outcomes, and (3) the number of hepatocytes traversed prior to establishing infection impacts immune responses. Alina Bätzilla showcased an impressive in vitro 3D blood-brain barrier model used to simulate and investigate leukocyte adherence to the endothelial wall during cerebral malaria. Konstantinos Kousis applied Bar-seq to better understand how immune therapies and drugs are impacted by antigen diversity, using P. vivax DBP haplotypes as a case study. Pierre Buffet used ex vivo and in vitro spleen models to mimic and investigate erythrocyte sensing, retention, and processing during malaria infection. Florian Bach compared changes in an individual’s immune response profile between an asymptomatic and a symptomatic infection over several years through the MICRDOP study. Simon Draper walked us through the evolution of the P. falciparum Rh5 blood-stage vaccine, including outcomes from the phase 1a trial in UK adults to the phase 1b trials in Tanzanian adults and children. Franklin Nuokpem dissected responses to the circumsporozoite protein, the main target of RTS, S and R21, in naturally exposed individuals.

Session 3: vectors and transmission

Sarah Reece emphasised that timing is everything for Plasmodium’s survival, where host and mosquito vector feeding rhythms impact parasite fitness and transmission. Lisa Verzier visualised the parasite’s life within the mosquito stage at the single-cell level and found that parasites interact most within the midgut and strongly associate with progenitor cells. Barbara Stokes demonstrated that parasites exhibit host-cell-specific transcriptional adaptations and that the location of the parasite impacts their potential for gametogenesis. Till Voss showed how investigating a protein thought to be dispensable for parasite proliferation, SET10, led to the discovery of proteins within the sample same complex that do impact genome replication. Selina Mussgnug identified that YTH.2 gene expression is impacted by sex and temperature, and it is essential for developmental progression. Emma Ganga showed how one protein, DCX, transcends multiple parasite stages within the mosquito and has varying functions in ookinetes, gametes and gametocytes.

Session 4: molecular and cellular biology

Ellen Bushell characterised two novel Plasmodium parasitophorous vacuole proteins that were critical virulence factors in a mouse model. Patrick Binder defined the mechanism by which parasites establish asynchrony with a biophysical model for nuclear resource allocation. Sophie Collier uncovered inheritance patterns and mechanisms of inheritance regulation of mitochondria and apicoplasts in Plasmodium. Yi Wei Chang displayed stunning Cryo-ET-generated images of the apicomplexan rhoptry secretion apparatus, delving layer by layer into the architecture of the parasite at the blood stage. Ilzat Ali described the localisation, function and organellar inheritance of P. falciparum striated fibre assemblins. Maryse Lebrun shifted focus with an investigation of the molecular mechanism of rhoptry secretion in Toxoplasma gondii. Francesca Florini demonstrated how var gene expression regulation can mediate parasite immune escape, including promoting a PfEMP1 silent state which renders the parasite invisible to the immune system.

Session 5: drug targets and resistance

Saman Habib linked mitochondria and apicoplast genome maintenance to P. falciparum exonucleases necessary during the blood stage. Roberto Mores Barros provided insights into how misinformed mass drug administration can impact parasite populations and select for resistant parasites in the unique setting of Porto Velho (Brazil), where the city hospital and laboratory are closely linked and have access to all cases within the city. Mukul Rawat defined compounds with potent dual action against both Plasmodium and Schistosoma and described the specific targets within P. falciparum. Laurent Dembele highlighted the importance of using wild-type parasites instead of lab strains in our studies for accurate representation of parasites circulating in endemic regions. They identified a protein that distinguishes between the P. vivax developing and hypnozoite stages. Madeline G. Dans delved into the impacts of inhibiting Plasmepsin V on parasite fitness and its promise as a future multistage antimalarial target. Julien Robert-Paganin identified the atypical P. falciparum myosin A protein as a potential and promising pharmaceutical antimalarial target. Amy Bei stressed the importance of understanding the impact of genetic diversity on antimalarial candidates through evaluating the functional impact of P. falciparum Rh5, CyRPA and Ripr diversity on immune evasion.

Aside from the engaging presentations, there were 155 posters spanning the diverse malaria fields, and of these, ten were awarded for their excellence. This brief report does not even begin to cover the hours, days, weeks, months and years of work that have gone into putting together the stories presented at BioMalPar XXI. This cohort’s commitment to producing high-quality research to combat the pressing issue of malaria is incredibly inspiring and gives me hope that one day we’ll pave the way towards a malaria-free future.

The EMBL Conference ‘BioMalPar XXI: biology and pathology of the malaria parasite’ took place between 20 – 22 May 2025 in Heidelberg, Germany.

Read also about the #EMBLMalaria poster prize winners and find out more about their research in another blog post from the meeting.

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