The Waller lab, together with Kathryn Lilley's lab in the Department of Biochemistry, and Julian Rayner's lab at the Cambridge Institute for Medical Research, have produced the most comprehensive map yet of where proteins are located inside the malaria parasite Plasmodium falciparum. Using hyperLOPIT, a spatial proteomics technique developed by the Lilley lab, the team assigned over 1,600 proteins to one of 24 compartments within the parasite and the red blood cell it infects. Despite decades of research on this parasite, most of its proteins still have no known function, so simply knowing where they sit in the cell is a useful starting point.
The map shows where the parasite has been most evolutionarily active. Newly evolved proteins are concentrated almost entirely at the interface between the parasite and the host red blood cell, while the parasite's core internal machinery is dominated by old, conserved proteins. Further analysis suggests that speciation in Plasmodium, where different animals serve as primary hosts, has been driven by changes in metabolic compartments, including a relic photosynthetic organelle, the apicoplast. The map also defines where current adaptive pressure is most concentrated in the cell as this parasite and its human hosts continue in their evolutionary arms race. Together, this data opens up new avenues to explore the biology of hundreds of previously uncharacterised proteins, some of which may turn out to be relevant to future drugs or vaccines.
Read the paper in Nature Communications: ‘The spatial proteome of the Plasmodium falciparum schizont illuminates the composition and evolutionary trajectories of its organelles’