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Screening of novel ligands for PfSR1, a putative GPCR-like receptor and identification of potential signaling pathways

Grant number: 21/12440-1
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): February 01, 2022
Effective date (End): July 31, 2022
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal researcher:Célia Regina da Silva Garcia
Grantee:Maneesh Kumar Singh
Supervisor abroad: Ralf Jockers
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Institut Cochin, France  
Associated to the scholarship:19/09490-7 - Screening of novel ligands for PfSR1, a putative GPCR-like receptor and identification of potential IP3 receptor in calcium signaling in the Plasmodium falciparum, BP.PD

Abstract

Current antimalarial compounds are failing rapidly due to emerging drug resistance Plasmodium strains. This requires urgent discovery of new antimalarial compounds and novel targets in the parasites. Our lab has identified four serpentine receptor-like proteins, and which could be a potential target for malaria intervention. Moreover, we still know very little about the functionality of these proteins. The signal transmission of G-protein coupled receptor (GPCR) proteins largely depends on the hydrolysis of either ATP or phosphatidylinositol (PI). Both ATP and PI can activate the intracellular calcium signaling which is crucial in triggering the various physiological processes in the human malaria parasite Plasmodium falciparum. In our preliminary study, we found one transmembrane protein PfSR1 has a strong binding affinity to melatonin, and it is expressed in the asexual stage as well. Based on our previous studies, we know that melatonin alters calcium mobilization, activates the cAMP-dependent protein kinase and the ubiquitin-proteasome system. Surprisingly, a potential melatonin receptor in Plasmodium is yet to be identified however, melatonin receptors in the mammalian system have been characterized as GPCR. To find a potential melatonin receptor, we are proposing to screen various ligands using a novel bioluminescence resonance energy transfer (BRET) system to study the physiological properties of PfSR1 in the mammalian system. (AU)

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