Last Updated: 21/07/2025
The role of three ApiAP2 transcription factors in controlling transcription in the intraerythrocytic and sexual cycle of Plasmodium falciparum
Objectives
*Original title in Portuguese: O papel de três fatores de transcrição ApiAP2 no controle na transcrição no ciclo intraeritrocítico e sexual de Plasmodium falciparum
This project proposes to address the participation of three transcription factors of the ApiAP2 family, PF3D7_1143100, PF3D7_1466400 and PF3D7_1007700, in controlling the transcription of genes in the intraerythrocytic and sexual phase of P. falciparum by investigating the effect of loss of function of these proteins on intra-erythrocytic development and in the mosquito.
The protozoan Plasmodium falciparum is responsible for the most severe forms of human malaria, the most vulnerable people being children under 5 years of age and pregnant women. To escape the host’s immune response, asexual forms of the parasite use antigenic variation of genes associated with virulence and sexual differentiation as a strategy to survive and ensure their transmission to the mosquito, where sexual reproduction occurs. The molecular basis behind this process is still poorly understood. By now a number of chromatin-modifying enzymes have been associated with both the process of antigenic variation and gametocyte formation. However, it is not known how the parasite controls these phenomena, nor the mechanisms that trigger these processes and the possible transcription factors that may be involved. Two conditions, “ON” and “OFF” will be compared for the expression of each target protein. For this, genetically modified parasite strains will be used that i) have the C-terminal region of the ApiAP2 proteins marked with a destabilization domain that can be stabilized by incubating the parasites with a molecule called Shield-1 or ii) have the sequence of glmS ribozyme located in the 3 UTR region of target transcripts, which induces self-cleavage in the presence of Glucosamine. These two gene silencing mechanisms render both the transcript and the protein regulatory. Since the proteins of interest will also have a HA marker, Chip-Seq will identify the specific sequences where these transcription factors bind. This study will contribute with new information about the transcription control in P. falciparum, and will probably point to new drug targets since i) the interference of a possible key process for the survival of the parasite makes it more vulnerable, and ii) ApiAP2 transcription factors are absent in the human host.
Mar 2017 — Nov 2020
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