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Effects of interferon-gamma on gene expression and splicing in leukocytes from chronic granulomatous disease patients

Grant number: 14/15920-0
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): January 15, 2015
Effective date (End): January 14, 2016
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Antonio Condino Neto
Grantee:Josias Soares de Brito
Supervisor: Rémy Bruggmann
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: University of Bern, Switzerland  


High-throughput RNA sequencing (RNA-seq) is a powerful method for discovering, profiling and quantifying RNA transcripts, turning into possible its use for indentifying splicing events. However, the need for RNA-seq data analysis and interpretation still remains a big hurdle for many research and clinical applications. One of the main goals of this project is to identify the differentially expressed genes in Chronic Granulomatous Disease (CGD) by in vitro treatment with IFN-g. CGD is a disease characterized by severe recurrent infections due to genetic defects that cause an impairment of the function of the human phagocyte NADPH oxidase system, a critical system for the generation of superoxide and other reactive oxygen intermediates and in the defense against pathogens. Our group has demonstrated that IFN-g interferes in the processing of the mRNA increasing the expression of CYBB gene encoding gp91-phox protein and acts at pre-transcriptional level increasing the amount of transcripts and proteins involved in the splicing process in healthy individuals and in CGD patients. By using RNA-seq technology and customized bioinformatics tools to specifically select genes based on a combination of expression change threshold and score cutoff relied on P values generated by statistical modeling, we aim to be able to identify different patterns in the dynamics of the splicing process and transcriptomic changes that occur during the processing of mRNAs that are induced by IFN-g in leukocytes from normal individuals and in patients with X-linked CGD caused by splicing defects. This proposed work aim to advance the understanding of the splicing mechanism that regulates the expression of genes related to the myeloid lineage (Fapesp Grant 2012/51094-2 and 2013/50460-8). (AU)

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Scientific publications
(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)
FRAZAO, JOSIAS B.; COLOMBO, MARTINO; SIMILLION, CEDRIC; BILICAN, ADEM; KELLER, IRENE; WUETHRICH, DANIEL; ZHU, ZHIQING; OKONIEWSKI, MICHAL J.; BRUGGMANN, REMY; CONDINO-NETO, ANTONIO; et al. Gene expression in chronic granulomatous disease and interferon-gamma receptor-deficient cells treated in vitro with interferon-gamma. Journal of Cellular Biochemistry, v. 120, n. 3, p. 4321-4332, . (14/15920-0)

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