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Genomics and post-genomics approaches to study the human malarial parasites Plasmodium vivax and Plasmodium falciparum in the Brazilian Amazon

Abstract

In spite of intense research, malaria remains the most devastating parasitic disease of mankind with ca. 200-300 annual million cases and 1.7-2.4 million deaths mostly in children below five years of age. In the particular case of Brazil, the Amazon region is responsible for almost all the clinical malaria attacks, which last year accounted for more than 600,000 cases with a socio-economical burden of aroundl00-200 million dollars. Remarkably, the two most prevalent malarial species, Plasmodium falciparum and P. vivax are sympatric in the Brazilian Amazon, offering a unique opportunity for comparative studies. In 1997 an International Consortium between The Sanger Centre, TIGR and Stanford University launched the Genome Project of P. falciparum. In this same year, the construction of a representative library of P. vivax was reported, initiating strictu sensu the genomic era of human malaria research. Significantly, the completion of the P. falciparum genome as well as major advances on the genome of P. vivax, were recently announced at the Eleventh Meeting of the Malaria Genome Consortium (Hinxton, June 5th_6th). We thus propose to use genomic and post-genomic approaches to accelerate the discovery of three main research areas in P. falciparum and P. vivax that we have been investigating through alternative methodologies for the last 10 years: virulence, population genetics and chemotherapy. Moreover, through the interaction with the Center for Bioinformatics at USP, we propose to create a malaria data bank of sequences and micro-array images (MaIDB) to fully exploit all this new biological information. Virulence: Sequencing of the subtelomeric regions of P. falciparum and P. vivax has revealed the existence of multi-gene families encoding virulent determinants. We propose to determine the genomic repertoire of these multigene families in the Brazilian Amazon through the sequencing of -10 Mbp obtained from parasites of infected patients in different regions. With this information, microarrays representing the "Brazilian" repertoire of virulent genes from P. vivax and P. falciparum will be constructed and used to determine the pattern of expression of malaria patients with different clinical spectra, including samples from Asia and Africa. These results should reveal expression patterns associated with symptomatic vs. non-symptomatic patients as well as patterns associated with falciparum infections compromising the lungs and kidneys, the most prevalent pathology associated with malaria in the Brazilian Amazon. Moreover, the analysis of expressed sequences can reveal common motifs that could represent the basis of future and rational approaches to develop new vaccines and/or drugs against malaria... (AU)

Scientific publications (9)
(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)
ROSANAS-URGELL, ANNA; MARTIN-JAULAR, LORENA; RICARTE-FILHO, JULIO; FERRER, MIREIA; KALKO, SUSANA; KIMURA, EDNA; DEL PORTILLO, HERNANDO A. Expression of non-TLR pattern recognition receptors in the spleen of BALB/c mice infected with Plasmodium yoelii and Plasmodium chabaudi chabaudi AS. Memórias do Instituto Oswaldo Cruz, v. 107, n. 3, p. 410+, MAY 2012. Web of Science Citations: 5.
RIS‚ M.; BARRERA‚ J.; MARTINS JR‚ D.C. U-curve: A branch-and-bound optimization algorithm for U-shaped cost functions on Boolean lattices applied to the feature selection problem. PATTERN RECOGNITION, v. 43, n. 3, p. 557-568, 2010.
ORJUELA-SANCHEZ, PAMELA; DE SANTANA FILHO, FRANKLIN SIMOES; MACHADO-LIMA, ARIANE; CHEHUAN, YONNE FRANCIS; FARIAS COSTA, MONICA REGINA; COSTA ALECRIM, MARIA DAS GRACAS; DEL PORTILLO, HERNANDO A. Analysis of Single-Nucleotide Polymorphisms in the crt-o and mdr1 Genes of Plasmodium vivax among Chloroquine-Resistant Isolates from the Brazilian Amazon Region. Antimicrobial Agents and Chemotherapy, v. 53, n. 8, p. 3561-3564, AUG 2009. Web of Science Citations: 42.
AZEVEDO‚ M.F.; DEL PORTILLO‚ H.A. Promoter regions of Plasmodium vivax are poorly or not recognized by Plasmodium falciparum. Malaria Journal, v. 6, n. 1, p. 20, 2007.
BARRERA‚ J.; CESAR‚ R.M.; HUMES‚ C.; MARTINS‚ D.C.; PATRÃO‚ D.F.C.; SILVA‚ P.J.S.; BRENTANI‚ H. A feature selection approach for identification of signature genes from SAGE data. BMC Bioinformatics, v. 8, n. 1, p. 169, 2007.
FERNANDEZ-BECERRA‚ C.; PEIN‚ O.; DE OLIVEIRA‚ T.R.; YAMAMOTO‚ M.M.; CASSOLA‚ A.C.; ROCHA‚ C.; SOARES‚ I.S.; DE BRAGANÇA PEREIRA‚ C.A.; DEL PORTILLO‚ H.A. Variant proteins of Plasmodium vivax are not clonally expressed in natural infections. Molecular Microbiology, v. 58, n. 3, p. 648-658, 2005.
SÁ‚ J.M.; NOMURA‚ T.; NEVES‚ J.A.; BAIRD‚ J.K.; WELLEMS‚ T.E.; DEL PORTILLO‚ H.A. Plasmodium vivax: allele variants of the mdr1 gene do not associate with chloroquine resistance among isolates from Brazil‚ Papua‚ and monkey-adapted strains. Experimental Parasitology, v. 109, n. 4, p. 256-259, 2005.
FERNANDEZ-BECERRA, CARMEN; AZEVEDO, MAURO F. DE; YAMAMOTO, MARCIO M.; DEL PORTILLO, HERNANDO A. Plasmodium falciparum: new vector with bi-directional promoter activity to stably express transgenes. Experimental Parasitology, v. 103, n. 1/2, p. 88-91, Jan. 2003.
MERINO‚ E.F.; FERNANDEZ-BECERRA‚ C.; MADEIRA‚ A.M.B.N.; MACHADO‚ A.L.; DURHAM‚ A.; GRUBER‚ A.; HALL‚ N.; DEL PORTILLO‚ H.A. Pilot survey of expressed sequence tags (ESTs) from the asexual blood stages of Plasmodium vivax in human patients. Malaria Journal, v. 2, n. 1, p. 21, 2003.

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