Towards understanding of expression control in Malaria parasites: from variant gene families in Plasmodium falciparum to pathogeny and inhibition of transmission

All species of Plasmodium encode variant gene families in their genome, which possess different purposes and often relate to immune invasion or pathogenic processes. In recent years, data accumulated pointing to a complex network of regulation of variant gene families at a transcriptional and post-transcriptional level. There have been investments in the function of specific putative plant-like transcription factors and chromatin modifiers to access their influence on variant gene expression. It could be shown that specific phylum-unique factors – AP2-O and AP2-EXP – participate in the enigmatic process of selective expression of determined members of variant gene families. Interestingly, these transcription factors are refractory to knockout, but do not interfere in vitro growth of Plasmodium falciparum under partial (~80%) knockdown. Nevertheless, higher levels of these factors are critical for later sexual stages, since partial knockdown abrogates effective development in the mosquito. Further, the project will approach the effect of temporary knockdown of the essential Exosome-RNAse PfRrp6 and the helicase PfRecQ01. In order to find roles of these enzymes also for transmission stages, the proposal sets to perform mosquito infection experiments, which will be conducted with the collaborators at Glasgow University. Using the same vector/transfectant/knockdown approach as for the chromatin modifiers and AP2 factors, investment will also be made in the chaperone-adaptor factors AHA2 and AHA4 from P. falciparum, contributing to the work of a group from São Carlos.

Project details

Basic Science

Jul 2022 — Jun 2024

Brazil