Last Updated: 24/03/2025
Analysis of the antimalarial properties of histone deacetylase inhibitors in wild-type Plasmodium falciparum and knockdown for nuclear protein PfMORC
Objectives
*Original title in Portuguese: Análise das propriedades antimaláricas de inibidores de desacetilases de histonas em Plasmodium falciparum selvagem e knockdown para proteína nuclear PfMORC
The project will address the screening of histone deacetylase inhibitors to analyze their effects on the parasitemia of Plasmodium falciparum cultures. In addition, this project will investigate by fluorescence microscopy the intracellular localization of the GPCR candidates in HEK293T cells treated with HDAC inhibitors.
Malaria is a disease caused by protozoan parasites of the genus Plasmodium that results in the death of hundreds of thousands of people every year. Due to the resistance that the etiological agent has acquired to available antimalarials, increasing research has been carried out on the biology of the parasite to elucidate its signaling pathways and discover targets for the development of new antimalarials. Histone deacetylases (HDACs) are important for chromatin condensation and regulation of gene expression. HDAC inhibitors have been used as antitumor and antiparasitic agents, and different HDAC inhibitors have been identified as inhibitors of the intraerythrocytic cycle of Plasmodium falciparum. In this context, new antimalarials can be discovered from screening assays of HDAC inhibitors. GPCRs (G-protein coupled receptors), present in several organisms, are characterized by the presence of 7 transmembrane domains and are targets of most of the drugs available on the market. Four serpentine receptors have been identified in the Plasmodium falciparum genome, named SR1, SR10, SR12 and SR25. The study of functional aspects of the GPCR candidates may contribute to elucidate aspects of Plasmodium biology, such as the signaling pathways involved in life cycle synchronicity and drug resistance.
Nov 2024 — Oct 2025
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