Analysis of metabolic regulatory networks in inflammation

• Grant number: 15/25825-8
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): March 01, 2016
• Effective date (End): February 28, 2018
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Fernando de Queiroz Cunha
• Grantee: Melissa Lever
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases, AP.CEPID

Abstract

The project will involve using computational methods to identify novel gene regulatory networks(GRNs) that coordinate immune cell metabolism during immune responses. The GRNs will be generated by integrating protein-protein interactions from public databases with RNA-seq and microarray datasets from immune cells undergoing a variety of inflammatory processes. By using methods such as statistical correlation analysis, the GRNs can be inferred from these datasets. These candidate GRNs will then be validated experimentally by members of F. Cunha's laboratory in order to confirm which genes are regulated by specific transcription factors or by an immune-related receptor. Once these GRNs have been validated, a secondary aim is to combine GRNs from different imune cells in order to find common GRN motifs. These GRN motifs can then be developed into mathematical models that will enable the simulation of gene expression dynamics. Interesting phenotypic predictions of the model, such as oscillations in gene expression, can then be tested experimentally and the outcome can be used to validate and refine the model. This will allow a quantitative understanding of how transcription factors and their targets function to control cell metabolism. Such an understanding of cell metabolism is imperative since cell metabolism controls cell fate decisions. It also offers opportunity for therapies that aim to modulate cell metabolism in order to direct the immune response to treat inflammatory disorders. (AU)

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)

RUSSO, PEDRO S. T.; FERREIRA, GUSTAVO R.; CARDOZO, LUCAS E.; BUERGER, MATHEUS C.; ARIAS-CARRASCO, RAUL; MARUYAMA, SANDRA R.; HIRATA, THIAGO D. C.; LIMA, DIOGENES S.; PASSOS, FERNANDO M.; FUKUTANI, KIYOSHI F.; LEVER, MELISSA; SILVA, JOAO S.; MARACAJA-COUTINHO, VINICIUS; NAKAYA, HELDER I. CEMiTool: a Bioconductor package for performing comprehensive modular co-expression analyses. BMC Bioinformatics, v. 19, FEB 20 2018. Web of Science Citations: 12.