Last Updated: 01/05/2025
PfGCaMP3 as a new tool to study Ca2 + signaling in the human Malaria parasite Plasmodium falciparum
Objectives
The main goal of this study is to advance the understanding of calcium (Ca²⁺) signaling in Plasmodium falciparum using a genetically engineered transgenic parasite line (PfGCaMP3) that enables real-time monitoring of intracellular Ca²⁺ dynamics without the limitations of traditional organic markers.
The key objectives are:
- Using PfGCaMP3 parasites to screen compound libraries for potential antimalarial drugs that affect Ca²⁺ signaling;
- Investigating Ca²⁺ signaling in gametocytes, which is a novel and underexplored phase of the parasite’s lifecycle;
- Deciphering the mechanism of action of Tumor Necrosis Factor (TNF) on P. falciparum, particularly its effects on parasitemia levels, Intracellular Ca²⁺ concentration, and Modulation of PfPCNA1 in a PfeIK1 knockout strain; and
- Evaluating TNF’s impact on parasite mitochondria, to explore its dual role in P. falciparum biology.
Studies of Ca²⁺ signaling in Plasmodium falciparum to date have primarily used organic molecules to measure cytoplasmic Ca²⁺ fluctuations. However, such molecules present significant disadvantages and limitations. To overcome these issues, a transgenic parasite line (PfGCaMP3) was developed, capable of monitoring Ca²⁺ oscillations without the need for prior labeling with organic compounds. This project aims to advance the understanding of Ca²⁺ signaling in P. falciparum using the PfGCaMP3 line.
The study will include the screening of potential antimalarial compounds from chemical libraries using this transgenic strain. In addition, it will explore Ca²⁺ signaling in gametocytes—an area of research that remains largely unexplored. The project also aims to elucidate the mechanism of action of Tumor Necrosis Factor (TNF) during the intra-erythrocytic cycle of P. falciparum, following previous observations of reduced parasitemia and increased intracellular Ca²⁺ after TNF treatment. To that end, the effects of TNF on parasitemia and PfPCNA1 modulation will be evaluated in a PfeIK1 knockout strain. Lastly, the potential impact of TNF on the mitochondria of P. falciparum will be assessed to further explore the dual behavior of this cytokine and the organelle’s involvement.
Aug 2017 — Jun 2020
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