PfGCaMP3 as a new tool to study calcium signaling in the Human Malaria parasite Plasmodium falciparum

Abstract

Ca2+ signaling studies in P. falciparum published so far have used organic molecules for measuring the Ca2+ changes in parasite cytoplasm. However, such molecules have serious disadvantages and limitations. To solve this problem we have created a line of transgenic parasites (PfGCaMP3) able to monitor the Ca2+ oscillations within the parasite without loading with organic molecules. The goal of this project is to better understand Ca2+ signaling mechanism in P. falciparum, by using the new transgenic parasites PfGCaMP3. As part of this aim, we propose using these novel parasites to screen potential antimalarial molecules present in libraries of compounds. PfGCaMP3 will also allows us to study the Ca2+ signaling in P. falciparum gametocytes, since there is no data until now about Ca2+ variations in this stage of the parasite. Additionally we will decipher the Tumor Necrosis Factor (TNF) action mechanism in P. falciparum intraerythrocytic cycle, since previous results from our group reported a decrease in parasitemia and an increase in intracellular Ca2+ concentration in the parasite after treatment with this cytokine. We will also evaluate the effects of TNF treatment in parasitemia and modulation PfPCNA1 in the PfeIK1 knockout strain. Finally, we will assess if treatment with TNF is able to affect P. falciparum mitochondria, thereby linking this organelle and the dual behavior of this cytokine. (AU)