Research Grants 99/07390-0 - Expressão gênica, Genomas - BV FAPESP
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Cooperation for Analysis of Gene Expression - CAGE

Abstract

Entire genomes and whole sets of ESTs of scientific and economically important micro-organisms, relevant model organisms and humans are rapidly becoming available. To take advantage of these enormous sets of genomic and EST sequences, several academic and industrial laboratories are developing technologies to analyze gene expression at RNA level on a genome wide basis using DNA microarrays, also called DNA chips. These techniques have potential to generate hundreds of data points for expression of tens of thousands of genes, whose impact in biological research might be revolutionary. Analyses of such huge amounts of data pose complex and unsolved problems of data storage, data mining and design of non linear gene state predictors. Altogether, these tasks require the coordinated collaboration of, by one side, computer scientists and mathematicians and, by the other, molecular biologists and biochemists. To this end, interdisciplinary teams of scientists are been organized in the countries that are presently leading the international genome research. In the State of São Paulo, F APESP has timely launched a genome program that was initiated by sequencing the genome of Xylella fastidiosa and is now been extended to genomes of other micro-organisms and ESTs of human cancer cells and plant cells of sugar cane. This F APESP initiative has established sufficient conditions to start a competitive local project of functional genomics by the technology of DNA microarrays. This proposal to F APESP aims to organize the "Cooperation for Analysis of Gene Expression", CAGE, an informal organization that will coordinate the collaborative efforts of molecular biologists of the Instituto de Química (IQ-USP) and computer scientists and mathematicians of the Instituto de Matemática e Estatística (IME-USP), to study gene expression by the DNA microarray technology. The immediate goal is to install a laboratory equipped for: a) high precision robotic printing of thousands of spots of cDNA sequences per cm2 onto glass slides (DNA chips); b) development of procedures to hybridize fluorescently labeled cDNA to DNA chips; c) high speed scanning of DNA chips with a computer-controlled inverted scanning fluorescent confocal rnicroscope. To have rapid access to this technology we are arranging a collaboration with the NIH Microarray Project, led by Drs. Jeffrey M. Trent and Michael Bittner from the Cancer Genetics Branch, National Human Genome Research Institute (NHGRI), NIH, Bethesda, MA, USA. The short and long term goals are to analyze gene expression in: a) several micro-organisms: Xylella fastidiosa, Dictyostelium discoideum, Xanthomonas campestris, Saccharomyces cerevisiae and Trypanosoma cruzi; b) human cancer cells and c) cell cycle of adrenocortical cells. For each case, rationale, specific objectives and experimental designing are presented in thematic projects respectively led by experienced molecular biologists from the IQ-USP. For storage and analyses of data, research projects are been devised by a team of senior investigators and their associates from the IME-USP, to devellop new tools for computational modeling, data mining, cluster analysis and design of non linear predictors. This area of mathematical and computational research will benefit from interactions with the team led by Dr. E. R. Dougherty in the NHGRI and Texas A&M University, Texas Center for Applied Technology, Department of Electrical Engineering, Texas, USA, with whom Dr. Junior Barrera, from IME-USP, has been maintaining ongoing research projects, for a few years. (AU)

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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)
MEIRELES, SIBELE I.; ESTEVES, GUSTAVO H.; HIRATA, JR., ROBERTO; PERI, SURAJ; DEVARAJAN, KARTHIK; SLIFKER, MICHAEL; MOSIER, STACY L.; PENG, JING; VADHANAM, MANICKA V.; HURST, HARRELL E.; et al. Early Changes in Gene Expression Induced by Tobacco Smoke: Evidence for the Importance of Estrogen within Lung Tissue. Cancer Prevention Research, v. 3, n. 6, p. 707-717, . (98/14335-2, 99/11962-9, 99/07390-0)
STOLF, BEATRIZ S.; SANTOS, MARIANA M. S.; SIMAO, DANIEL F.; DIAZ, JUAN P.; CRISTO, ELIER B.; HIRATA JÚNIOR, ROBERTO; CURADO, MARIA P.; NEVES, EDUARDO J.; KOWALSKI, LUIZ P.; CARVALHO, ALEX F.. Class distinction between follicular adenomas and follicular carcinomas of the thyroid gland on the basis of their signature expression. Cancer, v. 106, n. 9, p. 1891-1900, . (99/07390-0, 98/14335-2, 99/11962-9)
GOMES, LUCIANA I.; ESTEVES, GUSTAVO H.; CARVALHO, ALEX F.; CRISTO, ELIER B.; HIRATA JÚNIOR, ROBERTO; MARTINS, WALESKA K.; MARQUES, SARAH M.; CAMARGO, LUIZ P.; BRENTANI, HELENA; PELOSOF, ADRIANE; et al. Expression profile of malignant and nonmalignant lesions of esophagus and stomach: differential activity of functional modules related to inflammation and lipid metabolism. Cancer Research, v. 65, n. 16, p. 7127-7136, . (99/11962-9, 99/07390-0, 98/14335-2)
MEIRELES‚ S.I.; CRISTO‚ E.B.; CARVALHO‚ A.F.; HIRATA‚ R.; PELOSOF‚ A.; GOMES‚ L.I.; MARTINS‚ W.K.; BEGNAMI‚ M.D.; ZITRON‚ C.; MONTAGNINI‚ A.L.; et al. Molecular classifiers for gastric cancer and nonmalignant diseases of the gastric mucosa. Cancer Research, v. 64, n. 4, p. 1255, . (98/14335-2, 99/07390-0, 99/11962-9)

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