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

• Grant number: 21/02298-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2024
• End date: February 28, 2025
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Gerhard Wunderlich
• Grantee: Elaine Hellen Nunes Chagas
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The human malaria parasite Plasmodium falciparum expresses protein of the type PfEMP, which are variant proteins of the infected erythrocyte, which act as ligands for the endothelial receptors in capillaries, leading to the sequestration of erythrocytes as well as a malaria grave. Despite the advances made, the factors that orchestrate a mono-allelic expression of the "var" genes that encode between 50 and 60 genes within each genome of the parasite have not yet been fully identified. Previous studies have shown that the supposed transcription factor PfAP2-O influences the transcription of var genes and other multigene families. The temporary knockdown of PfAP2-O led to a complete loss of var transcriptional memory and led to a decrease in the cytoadherence of infected red blood cells. Likewise, you could see that another PfAP2 factor, AP2-exp, also interfered with the transcription of 'var' genes after partial knockdown. In the first 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. Here, we propose to elucidate factors that are associated with PfAP2-O and PfAP2-exp by a new method that allows the marking of factors with biotin around of PfAP2-O and PfAP2-exp. After selective biotinylation, as proteins that can be purified by streptavidin columns and analyzed by mass spectrometry. In this way, this project will increase our knowledge about the transcription of the virulence. It is referring to gene in the malaria parasite, which is identified as the most pathogenic, possibly leading to new targets of intervention that will collaborate for a better understanding in the performance of such genes, and possibly as block them so that there is a decrease in the transmission of plasmodium and consequently a decrease in the cases of the disease.