Functional genomics in Plasmodium

• Grant number: 07/52924-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: November 01, 2007
• End date: November 30, 2012
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Célia Regina da Silva Garcia
• Grantee: Célia Regina da Silva Garcia
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 10/51593-3 - Heterologous expression and biochemical characterization of apyrase from the parasite Plasmodium falciparum, BP.DD; 09/13672-1 - Dissecting the signaling machinery in Plasmodium falciparum, BP.PD

Abstract

The significance of this proposal is to investigate the adaptation of the parasite, where Plasmodium is capable of sensing the environment and using molecules derived from the host to signal the cell cycle. Using a bioinformatics approach we identified in the genome four candidates with serpentine receptors in Plasmodium falciparum. Briefly, this proposal is based on the importance of the upstream signaling paths (serpentine receptors) and downstream paths (kinases, phosphatases, etc.) in Plasmodium for the modulation of transduction signal coupled to survival and replication mechanisms of the parasite. An important aspect of the project emerged with results of the microarray in collaboration with Dr Elizabeth Winzeler, EUA, showing that PfEMP (VAR genes) has its genes activated when parasites P. falciparum were subjected to treatment with melatonin. Investigation with strains of parasites coming from patient samples (obtained from the strain banks of the Department of Parasitology, ICB, Dr. Gerard Wunderlich, São Paulo and Rondônia) and comparison with culture samples treated or not with hormone could provide vital information for the understanding of the mechanisms of the regulation of the expression of the VAR genes. One hypothesis is that the hormone could mimic a physiological situation and act in the regulation which is absent from the culture of Plasmodium falciparum. To unravel the paths of signal transduction from serpentine receptors in the membrane and target-proteins in the cytosol for the development of new drugs to combat malaria. To study the function of the genes, we plan to use bioinformatics, proteomics and systems Biology such as, for example, the use of synthetic genes with codon optimization to resolve the question of the difficulty of heterologous expression in Plasmodium. (AU)

Scientific publications

(6)

(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)

SCHUCK, DESIREE CIGARAN; RIBEIRO, RAMIRA YURI; NERY, ARTHUR A.; ULRICH, HENNING; GARCIA, CELIA R. S.. Flow Cytometry as a Tool for Analyzing Changes in Plasmodium falciparum Cell Cycle Following Treatment with Indol Compounds. Cytometry Part A, v. 79A, n. 11, p. 959-964, NOV 2011. (07/52924-0)

SCHUCK, DESIREE C.; FERREIRA, SABRINA B.; CRUZ, LAURA N.; DA ROCHA, DAVID R.; MORAES, MIRIAM S.; NAKABASHI, MYNA; ROSENTHAL, PHILIP J.; FERREIRA, VITOR F.; GARCIA, CELIA R. S.. Biological evaluation of hydroxynaphthoquinones as anti-malarials. Malaria Journal, v. 12, JUL 10 2013. (07/52924-0)

ALVES, EDUARDO; BARTLETT, PAULA J.; GARCIA, CELIA R. S.; THOMAS, ANDREW P.. Melatonin and IP3-induced Ca2+ Release from Intracellular Stores in the Malaria Parasite Plasmodium falciparum within Infected Red Blood Cells. Journal of Biological Chemistry, v. 286, n. 7, p. 5905-5912, FEB 18 2011. (07/52924-0)

MADEIRA, LUCIANA; GALANTE, PEDRO A. F.; BUDU, ALEXANDRE; AZEVEDO, MAURO F.; MALNIC, BETTINA; GARCIA, CELIA R. S.. Genome-Wide Detection of Serpentine Receptor-Like Proteins in Malaria Parasites. PLoS One, v. 3, n. 3, Mar. 2008. (07/52924-0)

SCHUCK, DESIREE CIGARAN; RIBEIRO, RAMIRA YURI; NERY, ARTHUR A.; ULRICH, HENNING; GARCIA, CELIA R. S.. Flow Cytometry as a Tool for Analyzing Changes in Plasmodium falciparum Cell Cycle Following Treatment with Indol Compounds. Cytometry Part A, v. 79A, n. 11, p. 6-pg., 2011-11-01. (07/52924-0)

CRUZ, LAURA N.; WU, YANG; CRAIG, ALISTER G.; GARCIA, CELIA R. S.. Signal transduction in Plasmodium-Red Blood Cells interactions and in cytoadherence. Anais da Academia Brasileira de Ciências, v. 84, n. 2, p. 555-571, JUN 2012. (07/52924-0)

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