MAP-X Reveals Hidden Protein Networks in Malaria Parasite
Source: https://blogs.ntu.edu.sg/science/2025/12/02/map-x-reveals-hidden-protein-networks-in-malaria-parasite/ Parent: https://blogs.ntu.edu.sg/science/
by Yvonne Teo | Dec 2, 2025 | Biology, People, School of Biological Sciences
Despite years of efforts and research, malaria continues to challenge global health, with drug-resistant Plasmodium falciparum threatening to undo decades of progress. Understanding the parasite at the molecular level is crucial to stay ahead. In a groundbreaking study published in Nature Microbiology, researchers introduce MAP-X, a powerful new method that maps protein–protein interactions across the parasite’s blood stages with unprecedented detail.
The work was led by Professor Zbynek Bozdech’s lab from the School of Biological Sciences (SBS), with Dr Samuel Pazicky as first author and Mr Seth Tjia as second author. It drew on a broad international collaboration involving experts from Germany, Singapore’s A*STAR IMCB and the UK, combining computational, proteomic and experimental strengths. MAP-X not only provides the most comprehensive view yet of how the parasite’s proteins interact but also opens the door to identifying potential vulnerabilities for next-generation antimalarial therapies.
Malaria parasites grow inside human red blood cells, and their survival depends on their protein complexes. The researchers developed a new method to predict protein complexes and showed the existence of some of them by fluorescence microscopy or structural predictions by AlphaFold. Image: Samuel Pazicky
Understanding the Parasite’s Protein Landscape
P. falciparum contains over 5,200 proteins, many of which form complexes that carry out essential cellular processes. However, the composition, dynamics, and stage-specific behaviour of these complexes remain largely unknown. Understanding how these proteins interact is crucial for revealing the molecular machinery that drives parasite growth and survival, and for identifying potential targets for next-generation antimalarial therapies.
Introducing MAP-X
MAP-X Workflow. Image: Samuel Pazicky
The team combined thermal proteome profiling (TPP) with machine learning to establish meltome-assisted profiling of protein complexes (MAP-X). TPP measures how intact proteins respond to heat.
As Dr Pazicky explains, “TTP examines the thermal stability of proteins in intact cells. When exposed to heat, proteins that interact with one another are destroyed in a similar manner.”
By analysing the melting behaviours of thousands of proteins and applying machine learning, MAP-X identifies proteins that form stable complexes. Across seven timepoints of the parasite’s blood-stage development, the method captured more than 20,000 protein interactions, producing a high-resolution atlas of how protein complexes form, change, and function.
Localization of a newly discovered protein complex. Image: Samuel Pazicky
New Biological Insights
Using MAP-X, the researchers confirmed known protein complexes and uncovered previously undescribed complexes and pathways specific to P. falciparum. Several predicted complexes were validated experimentally through fluorescence microscopy and pull-down assays.
Prof. Bozdech notes, “The interaction maps generated by MAP-X were able to predict previously unknown protein complexes. The existence of several of these complexes was further verified experimentally via fluorescence microscopy and pull-down assays.”
These insights could help pinpoint vulnerabilities in the parasite for future therapeutic targeting.
A Powerful Tool for Future Antimalarial and Biomedical Discoveries
As drug-resistant malaria strains continue to threaten global health, MAP-X offers a game-changing resource for identifying new therapeutic targets and guiding the development of next-generation antimalarials. Beyond malaria, this versatile method can be applied across a wide range of biological systems—from bacteria and other parasites to human tissues and plant cells—unlocking new possibilities for understanding protein networks and driving discoveries in molecular biology, drug development, and disease research.
Congratulations to Professor Zbynek Bozdech, Dr. Samuel Pazicky, Mr. Seth Tjia, and the entire collaborative team on this groundbreaking achievement, which highlights the pioneering work of SBS researchers at the forefront of malaria biology and molecular discovery.
Read the full paper here.