Functional genomics in Plasmodium

• Grant number: 11/51295-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: November 01, 2012
• End date: July 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Célia Regina da Silva Garcia
• Grantee: Célia Regina da Silva Garcia
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant(s): 18/09228-8 - 1st Malaria World Congress, AR.EXT; 18/07177-7 - EMU concedido no processo 2011/51295-5: image system, AP.EMU
• Associated scholarship(s): 17/14663-2 - PfGCaMP3 transgenic parasite as a tool to study the cytoplasmatic fluctuations of calcium in Plasmodium falciparum, BP.DD; 16/14411-0 - PfGCaMP3 as a new tool to study calcium signaling in the Human Malaria parasite Plasmodium falciparum, BP.PD; 16/18078-4 - Antimalarial activity of synthetic compounds: role of Plasmodium kinase signaling and development of transdermal drug delivery device, BP.PD; + associated scholarships 16/03952-0 - Role of two histone-fold domain proteins in Plasmodium parasites, BP.PD; 16/09185-1 - Calcium role in FIS1 and DRP1 genes activation on mitochondrial division of P. falciparum (WT) and parasite knockout strains for kinase PfPK7 , BP.IC; 16/08921-6 - Calcium signaling pathways dissection in Plasmodium falciparum by Pf GCaMP3 calcium-genetic marker parasites, BP.IC; 15/16483-6 - PfGCaMP3 transgenic parasite as a tool to study the cytoplasmatic fluctuations of calcium in Plasmodium falciparum, BP.DD; 14/16984-2 - Construction of GFP_PfSR10, candidate to serpentine receptor in Plasmodium falciparum, BP.IC; 14/14347-5 - Dissect signalling pathways in Plasmodium-host interaction: role of PfNF-YB transcription fator, BP.DD; 13/13361-1 - Deep Sequencing (RNA-seq) to detect differentially expressed genes involved in the modulation of cell cycle of Plasmodium falciparum, BP.PD; 09/14441-3 - Functional genomics in Plasmodium, BP.PD; 09/07155-4 - Elucidation of signaling and functional activities of serpentine receptors, PfSR12 and PfSR25., BP.PD - associated scholarships

Abstract

The elucidation of cell cycle and development control mechanisms of Plasmodium, the etiological agent of malaria, is crucial for development of new strategies for disease control. In this way, different ways of control either cell cycle or parasite development are propose to be studied in this project. Since our data generated in recent last years, including the identification of serpentine receptors, known in participating in a variety of cell processes, usually known as drug targets, will be better analyzed. Characterizing the RACK protein (receptor of activated protein kinase C) is also very important, whereas protein kinase C has not been/ound in Plasmodium falciparum. Moreover, the melatonin signaling pathway has bring us information about the participation of ubiquitin-proteasome system and protein kinase 7 as molecular effectors. Finally, detoxification mechanisms of heme in malaria parasites through hemeoxigenase will also be here evaluated. These proposed sub-projects enclose a range of cellular processes that participate in development and proliferation control of malaria parasite responsible for the most severe form of the disease, Plasmodium falciparum providing a contribution to knowledgement of diverse biological processes that enclose signaling pathways, gene expression control, cellular metabolism and others that participate in an indirect way. (AU)

Scientific publications

(23)

(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)

KOYAMA, FERNANDA C.; AZEVEDO, MAURO F.; BUDU, ALEXANDRE; CHAKRABARTI, DEBOPAM; GARCIA, CELIA R. S.. Melatonin-Induced Temporal Up-Regulation of Gene Expression Related to Ubiquitin/Proteasome System (UPS) in the Human Malaria Parasite Plasmodium falciparum. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 15, n. 12, p. 22320-22330, DEC 2014. (11/51295-5)

SCHUCK, DESIREE C.; JORDAO, ALESSANDRO K.; NAKABASHI, MYNA; CUNHA, ANNA C.; FERREIRA, VITOR F.; GARCIA, CELIA R. S.. Synthetic indole and melatonin derivatives exhibit antimalarial activity on the cell cycle of the human malaria parasite Plasmodium falciparum. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 78, p. 375-382, MAY 6 2014. (11/51295-5)

GARCIA, CELIA R. S.; ALVES, EDUARDO; PEREIRA, PEDRO H. S.; BARTLETT, PAULA J.; THOMAS, ANDREW P.; MIKOSHIBA, KATSUHIKO; PLATTNER, HELMUT; SIBLEY, L. DAVID. InsP(3) Signaling in Apicomplexan Parasites. CURRENT TOPICS IN MEDICINAL CHEMISTRY, v. 17, n. 19, p. 2158-2165, 2017. (11/51295-5)

CRUZ, LAURA N.; WU, YANG; ULRICH, HENNING; CRAIG, ALISTER G.; GARCIA, CELIA R. S.. Tumor necrosis factor reduces Plasmodium falciparum growth and activates calcium signaling in human malaria parasites. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1860, n. 7, p. 1489-1497, JUL 2016. (11/51295-5)

GONCALVES, FLAVIA; DE MORAES, MIRIAM SANTOS; FERREIRA, LORRAINE BRAGA; OLIVEIRA CARREIRA, ANA CLAUDIA; KOSSUGUE, PATRICIA MAYUMI; CIDREIRA BOARO, LETICIA CRISTINA; BENTINI, RICARDO; DA SILVA GARCIA, CELIA REGINA; SOGAYAR, MARI CLEIDE; ARANA-CHAVEZ, VICTOR ELIAS; et al. Combination of Bioactive Polymeric Membranes and Stem Cells for Periodontal Regeneration: In Vitro and In Vivo Analyses. PLoS One, v. 11, n. 3, MAR 31 2016. (10/17698-2, 11/51295-5, 11/21442-6)

CAMPOS AGUIAR, ANNA CAROLINE; PANCIERA, MICHELE; SIMAO DOS SANTOS, ERIC FRANCISCO; SINGH, MANEESH KUMAR; GARCIA, MARIANA LOPES; DE SOUZA, GUILHERME EDUARDO; NAKABASHI, MYNA; COSTA, JOSE LUIZ; GARCIA, CELIA R. S.; OLIVA, GLAUCIUS; et al. Discovery of Marinoquinolines as Potent and Fast-Acting Plasmodium falciparum Inhibitors with in Vivo Activity. Journal of Medicinal Chemistry, v. 61, n. 13, p. 5547-5568, JUL 12 2018. (11/51295-5, 14/25770-6, 15/18192-9, 13/25613-5, 13/07600-3)

BORGES-PEREIRA, LUCAS; MEISSNER, KAMILA ANNA; WRENGER, CARSTEN; GARCIA, CELIA R. S.. Plasmodium falciparum GFP-E-NTPDase expression at the intraerythrocytic stages and its inhibition blocks the development of the human malaria parasite. PURINERGIC SIGNALLING, v. 13, n. 3, p. 267-277, SEP 2017. (12/12807-3, 10/51593-3, 15/26722-8, 13/10288-1, 11/51295-5)

MORAES, MIRIAM S.; BUDU, ALEXANDRE; SINGH, MANEESH K.; BORGES-PEREIRA, LUCAS; LEVANO-GARCIA, JULIO; CURRA, CHIARA; PICCI, LEONARDO; PACE, TOMASINO; PONZI, MARTA; POZZAN, TULLIO; et al. Plasmodium falciparum GPCRlike receptor SR25 mediates extracellular K+ sensing coupled to Ca2+ signaling and stress survival. SCIENTIFIC REPORTS, v. 7, AUG 25 2017. (11/51295-5)

WU, YANG; CRUZ, LAURA N.; SZESTAK, TADGE; LAING, GAVIN; MOLYNEUX, GEMMA R.; GARCIA, CELIA R. S.; CRAIG, ALISTER G.. An external sensing system in Plasmodium falciparum-infected erythrocytes. Malaria Journal, v. 15, FEB 19 2016. (11/51295-5)

ALVES, EDUARDO; MALUF, FERNANDO V.; BUENO, VANIA B.; GUIDO, RAFAEL V. C.; OLIVA, GLAUCIUS; SINGH, MANEESH; SCARPELLI, PEDRO; COSTA, FAHYME; SARTORELLO, ROBSON; CATALANI, LUIZ H.; et al. Biliverdin targets enolase and eukaryotic initiation factor 2 (eIF2 alpha) to reduce the growth of intraerythrocytic development of the malaria parasite Plasmodium falciparum. SCIENTIFIC REPORTS, v. 6, FEB 26 2016. (11/51295-5, 11/21442-6, 13/07600-3)

AGUIAR, ANNA CAROLINE; DE SOUSA, LORENA R. F.; GARCIA, CELIA R. S.; OLIVA, GLAUCIUS; GUIDO, RAFAEL V. C.. New Molecular Targets and Strategies for Antimalarial Discovery. Current Medicinal Chemistry, v. 26, n. 23, p. 4380-4402, 2019. (11/51295-5, 13/07600-3)

LIMA, WANIA REZENDE; MARTINS, DAVID CORREA; PARREIRA, KLEBER SIMONIO; SCARPELLI, PEDRO; DE MORAES, MIRIAM SANTOS; TOPALIS, PANTELIS; HASHIMOTO, RONALDO FUMIO; GARCIA, CELIA R. S.. Genome-wide analysis of the human malaria parasite Plasmodium falciparum transcription factor PfNF-YB shows interaction with a CCAAT motif. ONCOTARGET, v. 8, n. 69, p. 113987-114001, DEC 26 2017. (15/01587-0, 11/51295-5, 11/50761-2)

SCARPELLI, PEDRO H.; TESSARIN-ALMEIDA, GIULLIANA; VICOSO, KENIA LOPES; LIMA, WANIA REZENDE; BORGES-PEREIRA, LUCAS; MEISSNER, KAMILA ANNA; WRENGER, CARSTEN; RAFAELLO, ANNA; RIZZUTO, ROSARIO; POZZAN, TULLIO; et al. Melatonin activates FIS1, DYN1, and DYN2 Plasmodium falciparum related-genes for mitochondria fission: Mitoemerald-GFP as a tool to visualize mitochondria structure. Journal of Pineal Research, v. 66, n. 2, MAR 2019. (12/12807-3, 11/51295-5, 14/14347-5, 15/26722-8)

ANA CAROLINA RENNÓ SODERO; BÁRBARA ABRAHIM-VIEIRA; PEDRO HENRIQUE MONTEIRO TORRES; PEDRO GERALDO PASCUTTI; CÉLIA RS GARCIA; VITOR FRANCISCO FERREIRA; DAVID RODRIGUES DA ROCHA; SABRINA BAPTISTA FERREIRA; FLORIANO PAES SILVA JR. Insights into cytochrome bc(1) complex binding mode of antimalarial 2-hydroxy-1,4-naphthoquinones through molecular modelling. Memórias do Instituto Oswaldo Cruz, v. 112, n. 4, p. 299-308, Abr. 2017. (11/51295-5)

ANA CAROLINA RENNÓ SODERO; BÁRBARA ABRAHIM-VIEIRA; PEDRO HENRIQUE MONTEIRO TORRES; PEDRO GERALDO PASCUTTI; CÉLIA RS GARCIA; VITOR FRANCISCO FERREIRA; DAVID RODRIGUES DA ROCHA; SABRINA BAPTISTA FERREIRA; FLORIANO PAES SILVA JR. Insights into cytochrome bc1 complex binding mode of antimalarial 2-hydroxy-1,4-naphthoquinones through molecular modelling. Memórias do Instituto Oswaldo Cruz, v. 112, n. 4, p. 299-308, 2017-04-00. (11/51295-5)

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)

LEE, ANDREW H.; DHINGRA, SATISH K.; LEWIS, IAN A.; SINGH, MANEESH K.; SIRIWARDANA, AMILA; DALAL, SEEMA; RUBIANO, KELLY; KLEIN, MATTHIAS S.; BASKA, KATELYNN S.; KRISHNA, SANJEEV; et al. Evidence for Regulation of Hemoglobin Metabolism and Intracellular Ionic Flux by the Plasmodium falciparum Chloroquine Resistance Transporter. SCIENTIFIC REPORTS, v. 8, SEP 11 2018. (11/51295-5)

SCARPELLI PEREIRA, PEDRO H.; CURRA, CHIARA; GARCIA, CELIA R. S.. Ubiquitin Proteasome System as a Potential Drug Target for Malaria. CURRENT TOPICS IN MEDICINAL CHEMISTRY, v. 18, n. 5, p. 315-320, 2018. (11/51295-5)

KOYAMA, FERNANDA C.; CARVALHO, THAIS L. G.; ALVES, EDUARDO; DA SILVA, HENRIQUE B.; DE AZEVEDO, MAURO F.; HEMERLY, ADRIANA S.; GARCIA, CELIA R. S.. The Structurally Related Auxin and Melatonin Tryptophan-Derivatives and their Roles in Arabidopsis thaliana and in the Human Malaria Parasite Plasmodium falciparum. Journal of Eukaryotic Microbiology, v. 60, n. 6, p. 646-651, NOV 2013. (11/51295-5)

ALVES, EDUARDO; IGLESIAS, BERNARDO A.; DEDA, DAIANA K.; BUDU, ALEXANDRE; MATIAS, TIAGO A.; BUENO, VANIA B.; MALUF, FERNANDO V.; GUIDO, RAFAEL V. C.; OLIVA, GLAUCIUS; CATALANI, LUIZ H.; et al. Encapsulation of metalloporphyrins improves their capacity to block the viability of the human malaria parasite Plasmodium falciparum. Nanomedicine-Nanotechnology Biology and Medicine, v. 11, n. 2, p. 351-358, FEB 2015. (11/51295-5)

KOYAMA, FERNANDA C.; AZEVEDO, MAURO F.; BUDU, ALEXANDRE; CHAKRABARTI, DEBOPAM; GARCIA, CELIA R. S.. Melatonin-Induced Temporal Up-Regulation of Gene Expression Related to Ubiquitin/Proteasome System (UPS) in the Human Malaria Parasite Plasmodium falciparum. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 15, n. 12, p. 11-pg., 2014-12-01. (11/51295-5)

BORGES-PEREIRA, LUCAS; CAMPOS, BRUNA R. K. L.; GARCIA, CELIA R. S.. The GCaMP3 - A GFP-based calcium sensor for imaging calcium dynamics in the human malaria parasite Plasmodium falciparum. METHODSX, v. 1, p. 4-pg., 2014-01-01. (11/51295-5)

RENNO SODERO, ANA CAROLINA; ABRAHIM-VIEIRA, BARBARA; MONTEIRO TORRES, PEDRO HENRIQUE; PASCUTTI, PEDRO GERALDO; GARCIA, CELIA R. S.; FERREIRA, VITOR FRANCISCO; DA ROCHA, DAVID RODRIGUES; FERREIRA, SABRINA BAPTISTA; SILVA-, FLORIANO PAES, JR.. Insights into cytochrome bc(1) complex binding mode of antimalarial 2-hydroxy-1,4-naphthoquinones through molecular modelling. Memórias do Instituto Oswaldo Cruz, v. 112, n. 4, p. 10-pg., 2017-04-01. (11/51295-5)

Filed patent(s) as a result of this research project