Exploring the interaction factors of two chromatin regulatory proteins involved in the control of virulence gene transcription in the malaria parasite Plasmodium falciparum

The human malaria parasite Plasmodium falciparum expresses PfEMP-type proteins, which are variant proteins on infected erythrocytes that function as ligands for endothelial receptors in capillaries, leading to erythrocyte sequestration as well as severe malaria. Despite recent significant advances, the factors that orchestrate the monoallelic expression of the “var” genes that encode between 50 to 60 genes within each parasite genome have not yet been fully identified. Previous studies have demonstrated that the putative transcription factor PfAP2-O influences the transcription of var genes and also other multigene families. Temporary knockdown of PfAP2-O led to a complete loss of var transcriptional memory and also led to a decrease in cytoadherence of infected red blood cells. Likewise, this project aimed to observe that another PfAP2 factor, AP2-exp, also interfered with the transcription of ‘var’ genes after partial knockdown. In early proteomic analyzes by co-immunoprecipitation, both factors did not interact with histones or other factors that bind directly to DNA, which raises the question of how the factors act at the cellular level. In this way, this project will increase current knowledge about the transcription of the virulence gene in the malaria parasite, which is identified as the most pathogenic, possibly leading to new intervention targets that will contribute to a better understanding of the action of such genes and possibly how block them so that there is a reduction in the transmission of Plasmodium and consequently a reduction in cases of the disease.

Project details

Basic Science

Mar 2024 — Feb 2025

Brazil