The spatial proteome of the Plasmodium falciparum schizont illuminates the composition and evolutionary trajectories of its organelles
Year: 2025
Type: preprint
Abstract: 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 resolved 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.
Institution: University of Cambridge
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Ross Waller Symbiosis in Aquatic Systems Initiative Investigator Award, Perkinsids as new model organisms to understand the basis of parasitism, Cellular dissection of Plasmodium falciparum erythrocyte invasion, The proteomic architectures of apicomplexan cells: the molecular complexity of pathogens revealed, What determines protein abundance in plants?
OpenAlex ID: W4416766272