Screening of novel ligands for PfSR1, a putative GPCR-like receptor and identification of potential IP3 receptor in calcium signaling in the Plasmodium falciparum

• Grant number: 19/09490-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2019
• End date: May 31, 2024
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Célia Regina da Silva Garcia
• Grantee: Maneesh Kumar Singh
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/08684-7 - Decoding Plasmodium signaling at molecular level as a new tool to the development of new antimalarials, AP.TEM
• Associated scholarship(s): 21/12440-1 - Screening of novel ligands for PfSR1, a putative GPCR-like receptor and identification of potential signaling pathways, BE.EP.PD

Abstract

The presence of serpentine receptors in protozoan parasites were unknown until Madeira et. al., have performed a genome-wide search for proteins containing 7-transmembrane proteins and identified four serpentine receptor-like proteins. However, signal transmission through these GPCR-like proteins is still unknown and the ligands that trigger the signal are yet to identify. The signal transmission of 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 to in triggering the various physiological processes in P. falciparum. The endoplasmic reticulum (ER) has been identified as a significant calcium store, but other potential calcium storage organelles include the Golgi, the mitochondrion, the food vacuole and potentially the apicoplast as well. Physiological and pharmacological evidence suggests that calcium signaling activated downstream to PLC by inositol triphosphate (IP3). In spite of the several pharmacological shreds of evidence of the canonical IP3 pathway, a putative IP3 receptor is yet to identify in the P. falciparum. Taking the diversity of Ca2+-regulatory components, it is evident that further research is fundamental in terms of the development of potential drug targets for clinical use. In this study, we are proposing to identify the ligand for PfSR1 and also search the IP3 receptor candidates in the P. falciparum.

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SINGH, MANEESH KUMAR; DE MENEZES DIAS, BARBARA KARINA; GARCIA, CELIA R. S.. Role of Melatonin in the Synchronization of Asexual Forms in the Parasite Plasmodium falciparum. BIOMOLECULES, v. 10, n. 9, SEP 2020. (17/08684-7, 19/09490-7)

MALLAUPOMA, LENNA ROSANIE CORDERO; DIAS, BARBARA KARINA DE MENEZES; SINGH, MANEESH KUMAR; HONORIO, RUTE ISABEL; NAKABASHI, MYNA; KISUKURI, CAMILA DE MENEZES; PAIXAO, MARCIO WEBER; GARCIA, CELIA R. S.. Decoding the Role of Melatonin Structure on Plasmodium falciparum Human Malaria Parasites Synchronization Using 2-Sulfenylindoles Derivatives. BIOMOLECULES, v. 12, n. 5, p. 15-pg., 2022-05-01. (18/12986-1, 17/08684-7, 19/09490-7)

SINGH, MANEESH K.; TESSARIN-ALMEIDA, GIULLIANA; DIAS, BARBARA K. M.; PEREIRA, PEDRO SCARPELLLI; COSTA, FAHYME; PRZYBORSKI, JUDE M.; GARCIA, CELIA R. S.. A nuclear protein, PfMORC confers melatonin dependent synchrony of the human malaria parasite P. falciparum in the asexual stage. SCIENTIFIC REPORTS, v. 11, n. 1, JAN 21 2021. (17/08684-7, 19/09490-7, 11/51295-5, 18/07177-7)

BORGES-PEREIRA, LUCAS; DIAS, BARBARA K. M.; SINGH, MANEESH KUMAR; GARCIA, CELIA R. S.. Malaria parasites and circadian rhythm: New insights into an old puzzle. CURRENT RESEARCH IN MICROBIAL SCIENCES, v. 2, p. 3-pg., 2021-12-01. (17/08684-7, 18/07177-7, 16/14411-0, 19/09490-7)