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Role of epigenetic changes induced by SCFAs in intestinal epithelial cells

Grant number: 15/50379-1
Support type:Regular Research Grants
Duration: November 01, 2015 - April 30, 2017
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Cooperation agreement: BBSRC, UKRI - FAPPA
Principal researcher:Marco Aurélio Ramirez Vinolo
Grantee:Marco Aurélio Ramirez Vinolo
Principal researcher abroad: Patrick Daniel Varga-Weisz
Institution abroad: Babraham Institute, England
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


In the present project, we wish to lest the hypothesis that SCFA regulate innate immunity of intestinal epithelial cells (enterocytes and related cells) by affecting histone modifications, especially modifications that may metabolically directly relate to SCFA, such as lysine acetylation and crotonylation. To test our ideas we will employ intestinal organoid culture ("mini-guts"), mouse models and transcriptome and chromatin analysis to examine the effect of SCFA directly on intestinal epithelial cells. In vivo experiments in which mice will be treated directly or indirectly (fibre) with SCFAs will also be performed in orther to analyse the relevance of the findings in vitro. To reach the proposed aims, we plan the exchange of three graduation students between the research groups and visits of the researchers involved in this project. We will also promote workshops to increase and to strengthen the scientific collaborations. (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)
KAZAKEVYCH, JURI; DENIZOT, JEREMY; LIEBERT, ANKE; PORTOVEDO, MARIANA; MOSAVIE, MIA; JAIN, PAYAL; STELLATO, CLAUDIA; FRASER, CLAIRE; CORREA, RENAN OLIVEIRA; CELESTINE, MARINA; et al. Smarcad1 mediates microbiota-induced inflammation in mouse and coordinates gene expression in the intestinal epithelium. Genome Biology, v. 21, n. 1, . (15/50379-1)
FELLOWS, RACHEL; DENIZOT, JEREMY; STELLATO, CLAUDIA; CUOMO, ALESSANDRO; JAIN, PAYAL; STOYANOVA, ELENA; BALAZSI, SZABINA; HAJNADY, ZOLTAN; LIEBERT, ANKE; KAZAKEVYCH, JURI; et al. Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. NATURE COMMUNICATIONS, v. 9, . (12/10653-9, 15/14105-4, 15/50379-1)

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