Use of PfGCaMP3 genetic tools, knockouts of GPCR-like PfSR25 and PfeIK1 kinase to study stages of the Plasmodium falciparum cell cycle: GSK drug screening

Plasmodium falciparum is part of the genus Plasmodium, which also includes other species that cause malaria. Among the species of this genus, P. falciparum is the one that leads to the most severe forms of the disease. Despite advances in malaria control, a major challenge remains due to the spread of parasites resistant to antimalarial drugs. It was reported in previous works that the melatonin of the vertebrate host, the variation in the extracellular concentration of potassium ions (K+) and the variation of intracellular calcium ions (Ca2+) have the capacity to activate intracellular cascades of P. falciparum. For this, transgenic parasites will be used: PfGCaMP3 (P. falciparum that constitutively expresses calcium ion sensor) in assays to evaluate whether the compounds selected from the initial screening of the GSK library have the capacity to alter the cytosolic concentration of Ca2+ and if this alteration occurs when the parasites are subjected to variation in extracellular K+ concentration; knockout for GPCR-like PfSR25 in an assay of invasion and egress of merozoites in red blood cells in the presence and absence of previously selected GSK compounds and; knockout of PfeIK1 (essential kinase for melatonin action in P. falciparum) in cytoadhesion assays in the presence and absence of melatonin.

Project details

Basic Science

Jan 2021

Brazil