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Dissecting the molecular mechanism for activation of Plasmodium falciparum serpentine receptor 12 in mammalian systems

Grant number: 18/06729-6
Support Opportunities:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): September 03, 2018
Effective date (End): July 02, 2019
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Célia Regina da Silva Garcia
Grantee:Pedro Henrique Scarpelli Pereira
Supervisor: Michel Bouvier
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Université de Montréal, Canada  
Associated to the scholarship:17/16307-9 - Dissecting the role of mitochondria division in cell cycle control of P. falciparum and drug resistance profiling of resistant strains, BP.DD


The project described here aims the characterization of the serpentine receptor 12 (PfSR12) of Plasmodium falciparum parasites. Unlike what was described in literature by bioinformatics experiments that showed PfSR12 as a purinergic receptor, we did not observe release of Ca2+ in our HEK297T system after purine treatments, but we did see a statistically significant response in Ca2+ release after thrombin addition to the cell culture. The indications that PfSR12 would be a thrombin receptor are of great importance, since parasite proteins capable of interacting with molecules of the host coagulation system are not yet known, and presence of protease-activated receptors in parasites is extremely rare. After the identification of thrombin as a ligand for PfSR12, we verified the action of this protein in a culture of in vitro P. falciparum. Supplementation of the culture medium with thrombin did not alter the duration of the parasite cycle, the total time of each stage of the cycle, or the parasite's morphology. However, an increase in parasitemia was observed in cultures incubated with thrombin when compared to non-supplemented cultures. We have reasons to believe that thrombin interact directly with the parasite, influencing the egress/invasion process of new cells. The action of thrombin can be mediated by PfSR12, which induces a signaling cascade that culminates in an increased efficiency of the invasion/egress process, or even in the formation of new cells. The experiments described in this project will allow us to define molecular aspects of thrombin and SR12 signaling pathway. (AU)

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