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Peer-reviewedCC BYNature Communications

The spatial proteome of the Plasmodium falciparum schizont illuminates the composition and evolutionary trajectories of its organelles

5 affiliations
  1. 1Department of Biochemistry, University of Cambridge, Cambridge, UK. [email protected]
  2. 2Department of Biochemistry, University of Cambridge, Cambridge, UK
  3. 3Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
  4. 4Cambridge Centre for Proteomics, Department of Biochemistry, University of Cambridge, Cambridge, UK
  5. 5Department of Biochemistry, University of Cambridge, Cambridge, UK. [email protected]

Abstract

Malaria is caused by apicomplexan parasites of the genus Plasmodium, with all malaria symptoms and pathology caused by parasite stages that develop within, or transit between, host erythrocytes. The ability of Plasmodium cells to parasitise erythrocytes depends on distinctive intracellular compartments associated with invasion, as well as the development of unique cellular niches within the infected host cell. However, our understanding of the biology of the malaria parasite is limited by the fact that a large proportion of the parasite's proteome has no known cellular location or function. To address this problem, we have generated comprehensive high-resolution maps of protein subcellular localisation for the invasive stage of the erythrocytic life cycle of Plasmodium falciparum, the major cause of malaria mortality. Using the spatial proteomics technique hyperplexed Localisation of Organelle Proteins by Isotopic Tagging (hyperLOPIT) we generated data for 3000 P. falciparum proteins expressed in late schizont stages. Our hyperLOPIT data resolve 24 distinct cellular niches, and using supervised machine-learning we can classify 1646 proteins into one of these compartments including exported sites within the host cell. Through comparative genomic analyses our data resolve the spatial patterns of cell evolution that have shaped the development of Plasmodium species and ongoing adaptive pressures and responses that challenge our efforts to manage these major disease-causing organisms.

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BibTeX
@article{chisholm2026spatial,
  title = {{The spatial proteome of the Plasmodium falciparum schizont illuminates the composition and evolutionary trajectories of its organelles}},
  author = {Scott A. Chisholm and Victor Flores and Alison Kemp and Lisa M. Breckels and Luděk Kořený and Nicolas Dos Santos Pacheco and Konstantin V. Barylyuk and Anna Kuroshchenkova and Kathryn Susan Lilley and Julian C. Rayner and Ross F. Waller},
  journal = {Nature Communications},
  year = {2026},
  month = may,
  doi = {10.1038/s41467-026-73664-2},
  url = {https://doi.org/10.1038/s41467-026-73664-2},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - The spatial proteome of the Plasmodium falciparum schizont illuminates the composition and evolutionary trajectories of its organelles
AU  - Scott A. Chisholm
AU  - Victor Flores
AU  - Alison Kemp
AU  - Lisa M. Breckels
AU  - Luděk Kořený
AU  - Nicolas Dos Santos Pacheco
AU  - Konstantin V. Barylyuk
AU  - Anna Kuroshchenkova
AU  - Kathryn Susan Lilley
AU  - Julian C. Rayner
AU  - Ross F. Waller
PY  - 2026
DA  - 2026/05/30
JO  - Nature Communications
DO  - 10.1038/s41467-026-73664-2
UR  - https://doi.org/10.1038/s41467-026-73664-2
AB  - Malaria is caused by apicomplexan parasites of the genus Plasmodium, with all malaria symptoms and pathology caused by parasite stages that develop within, or transit between, host erythrocytes. The ability of Plasmodium cells to parasitise erythrocytes depends on distinctive intracellular compartments associated with invasion, as well as the development of unique cellular niches within the infected host cell. However, our understanding of the biology of the malaria parasite is limited by the fact that a large proportion of the parasite's proteome has no known cellular location or function. To address this problem, we have generated comprehensive high-resolution maps of protein subcellular localisation for the invasive stage of the erythrocytic life cycle of Plasmodium falciparum, the major cause of malaria mortality. Using the spatial proteomics technique hyperplexed Localisation of Organelle Proteins by Isotopic Tagging (hyperLOPIT) we generated data for 3000 P. falciparum proteins expressed in late schizont stages. Our hyperLOPIT data resolve 24 distinct cellular niches, and using supervised machine-learning we can classify 1646 proteins into one of these compartments including exported sites within the host cell. Through comparative genomic analyses our data resolve the spatial patterns of cell evolution that have shaped the development of Plasmodium species and ongoing adaptive pressures and responses that challenge our efforts to manage these major disease-causing organisms.
SN  - 2041-1723
ER  -