Last Updated: 11/11/2024
PfGCaMP3 transgenic parasite as a tool to study the cytoplasmatic fluctuations of calcium in Plasmodium falciparum
Objectives
This project aims to study the dynamics of Ca2+ in the P. falciparum malaria parasite using the transgenic parasite PfGCaMP3, developed by the group, to analyze the role of the endoplasmic reticulum and mitochondria in the homeostasis and signaling of Ca2+ during intraerythrocytic stages of the parasite. Furthermore, compounds with structures similar to melatonin will be evaluated using PfGCaMP3 for their antimalarial capability, which may contribute to developing new strategies to combat malaria.
About 40% of the world population lives in endemic areas of malaria, a disease that mainly affects developing countries such as those in Africa and other countries under development. The etiological agent of malaria is Plasmodium, an Apicomplexan parasite, and the species P. falciparum is responsible for the most clinically severe manifestations of the disease. Transmission between vertebrate hosts occurs through Anopheles mosquitoes. The life cycle of Plasmodiumalternates between two hosts: (i) mosquitoes, where mating occurs; (ii) vertebrates, in which the parasite invades hepatocytes and then erythrocytes, multiplying asexually.
Studies from the laboratory show that calcium is the second messenger activated through the melatonin signaling pathway, and this activation culminates in the timing of the parasites during the intraerythrocytic phase. In parasites of the Apicomplexa phylum, calcium plays an important role in the secretion of micronemes during cell motility, invasion, and egress from the host cell, as well as in cell differentiation. Several studies have shown evidence of the existence of two distinct compartments of calcium stores in Plasmodium: the endoplasmic reticulum and an acidic compartment. The group demonstrated that mitochondria participate in calcium sequestration when the parasite is exposed to a high cytoplasmic concentration of this ion. Highly invasive protocols are used for loading the parasite with calcium markers to study the dynamics of calcium in the malaria parasite, P. falciparum, and these protocols do not enable distinguishing between the signals from the host cell and the parasite.
Mar 2018 — Dec 2019
