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Decoding Plasmodium signaling at molecular level as a new tool to the development of new antimalarials

Grant number: 17/08684-7
Support type:Research Projects - Thematic Grants
Duration: February 01, 2019 - January 31, 2024
Field of knowledge:Biological Sciences - Biochemistry - Biochemistry of Microorganisms
Principal researcher:Célia Regina da Silva Garcia
Grantee:Célia Regina da Silva Garcia
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Fabio Trindade Maranhão Costa ; Maria Regina D'Império Lima
Associated grant(s):19/05708-8 - Calcium signaling in Plasmodium falciparum gametocytes, AV.EXT
21/06607-0 - Multi-user equipment approved in grant 2017/08684-7: BRET, AP.EMU
Associated scholarship(s):22/06132-5 - Construction of Tagging and Knockdown Systems of the Serpentine Receptor 10 (SR10) in Plasmodium falciparum, BP.IC
22/06187-4 - Construction of aptamer based knockdown of apetela2 nuclear protein (AP2) in Plasmodium falciparum, BP.IC
22/02317-0 - Studies of GPCR-like PfSR12 signal transduction mechanisms in mammalian cells and in Plasmodium falciparum, BP.PD
+ associated scholarships 21/11213-1 - Decoding aspects of Plasmodium cell and molecular biology as a tool to develop new antimalarials, BP.TT
20/08988-9 - Evaluation of compounds with antimalarial potential and study of the signal transduction mechanism of GPCR (G-Protein Coupled Receptor) like PfSR25 in Plasmodium falciparum, BP.DD
19/27121-9 - Maintenance of Laboratory of Cell Biology and cell cultivation HEK293T., BP.TT
19/08974-0 - Maintenance of Cell Biology Laboratory and culture of HEK293T cells, BP.TT
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 - associated scholarships


Malaria stands as the third most dangerous infectious disease after HIV/AIDS and tuberculosis that afflict mankind. The last decade studies pointed that pathogens have developed sophisticated cell signaling networks that allow for both cell-cell communication as well as sensing the external environment. In this direction, single cell protozoan parasites have to develop systems to withstand relatively large alterations in their external environments, including existing in the mammalian host with complex defense systems. In addition to depicting a complex biology, with a sexual and asexual developmental stages, malaria parasite, is exposed to distinct microenvironments within the vector cycle as well as during its development inside a vertebrate. The overall objective of this project is to understand how the parasite detects signaling from its milieu, what are the molecular components involved in transducing this signaling. We recently reported that purinergic signaling could be involved in TNF perception by P. falciparum. We plan to dissect the involvement of purinergic receptor signaling in P. falciparum cell cycle thus unraveling what is the participation of a P2X7 receptor in TNF signaling. We will use the PfGCaMP3 parasites as well as other molecular and cellular tools to understand signaling pathways in malaria parasite aiming to disrupt this signaling. (AU)

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Scientific publications (11)
(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)
DOS SANTOS, BENEDITO M.; PEREIRA, PEDRO H. S.; GARCIA, CELIA R. S.. Molecular basis of synchronous replication of malaria parasites in the blood stage. Current Opinion in Microbiology, v. 63, p. 210-215, . (17/08684-7, 20/08988-9)
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, . (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, . (11/51295-5, 18/07177-7, 17/08684-7, 19/09490-7)
BORGES-PEREIRA, LUCAS; THOMAS, SAMANTHA J.; DOS ANJOS E SILVA, AMANDA LAIZY; BARTLETT, PAULA J.; THOMAS, ANDREW P.; GARCIA, CELIA R. S.. The genetic Ca2+ sensor GCaMP3 reveals multiple Ca2+ stores differentially coupled to Ca2+ entry in the human malaria parasite Plasmodium falciparum. Journal of Biological Chemistry, v. 295, n. 44, p. 14998-15012, . (16/14411-0, 18/07177-7, 17/08684-7)
DEDA, DAIANA K.; IGLESIAS, BERNARDO A.; ALVES, EDUARDO; ARAKI, KOITI; GARCIA, CELIA R. S.. Porphyrin Derivative Nanoformulations for Therapy and Antiparasitic Agents. Molecules, v. 25, n. 9, . (17/08684-7, 18/07177-7, 18/21489-1)
DIAS, BARBARA K. M.; NAKABASHI, MYNA; ALVES, MARINA RANGEL RODRIGUES; PORTELLA, DANIELLE PAGLIAMINUTO; DOS SANTOS, BENEDITO MATHEUS; ALMEIDA, FAHYME COSTA DA SILVA; RIBEIRO, RAMIRA YURI; SCHUCK, DESIREE C.; JORDAO, ALESSANDRO KAPPEL; GARCIA, CELIA R. S.. ThePlasmodium falciparumeIK1 kinase (PfeIK1) is central for melatonin synchronization in the human malaria parasite. Melatotosil blocks melatonin action on parasite cell cycle. Journal of Pineal Research, v. 69, n. 3, . (17/08684-7, 18/07177-7)
SCARPELLI, PEDRO H.; PECENIN, MATEUS F.; GARCIA, CELIA R. S.. Intracellular Ca2+ Signaling in Protozoan Parasites: An Overview with a Focus on Mitochondria. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 1, . (18/07177-7, 17/08684-7)
SANTOS, BENEDITO M. DOS; GONZAGA, DANIEL T. G.; DA SILVA, FERNANDO C.; FERREIRA, VITOR F.; GARCIA, CELIA R. S.. Plasmodium falciparum Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development. BIOMOLECULES, v. 10, n. 8, . (17/08684-7)

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