11December2018

ECCO Grant Study Synopsis: Federica Ungaro

Federica Ungaro, ECCO Grant Winner

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Definition of IBD-associated gut virome via next-generation sequencing: Novel insights for disease onset and treatments

 

Federica UngaroFederica Ungaro
© Federica Ungaro

Aim of Research

Viral infections have been reported to be the primary trigger in many diseases. Preliminary results from RNA-seq analysis performed on mucosal biopsies of patients with active Crohn’s Disease (CD) or Ulcerative Colitis (UC) and healthy controls revealed indicated an IBD-specific viral signature, characterised by increased levels of viral RNAs, especially in patients with UC.

Although analyses on gut virome composition are available, to date nobody has described which viruses are involved in IBD onset. We propose characterising the viral composition of gut mucosal samples from early-diagnosed patients with IBD and healthy subjects by exploiting transcriptomic analysis. Moreover, through RNA silencing experiments, we will investigate whether the inhibition of viral-specific RNAs may be beneficial in mucosal biopsies from patients with active IBD. Results obtained from this study are expected to lead to the unveiling of a novel concept depicting IBD aetiopathogenesis as related to specific viral infections. This will arguably offer new therapeutic insights and promote the search for antiviral drugs for the treatment of IBD.

Methodology

We will exploit publicly available RNA-seq data on mucosal samples derived from patients with early-diagnosed UC or CD and age-matched healthy controls. After the identification of viral sequences by metagenomics, we will perform siRNA-mediated silencing of the resulting upregulated transcripts in mucosal biopsies collected from a second cohort of patients with both active CD and UC. In parallel, the effects of viral-specific RNA silencing on mucosal biopsies will be evaluated in terms of gene expression via RNA-seq analysis. We will exploit publicly available RNA-seq data on mucosal samples derived from patients with early-diagnosed UC or CD and age-matched healthy controls. After the identification of viral sequences by metagenomics, we will perform siRNA-mediated silencing of the resulting upregulated transcripts in mucosal biopsies collected from a second cohort of patients with both active CD and UC. In parallel, the effects of viral-specific RNA silencing on mucosal biopsies will be evaluated in terms of gene expression via RNA-seq analysis.

Proposed timing

In the first 2 months we will select the publicly available data sets constituting the first cohort of patients with active and early-diagnosed IBD and finalise the bioinformatics analysis for identification of the virome signature of these patients. In the following 8 months, we will collect biopsies from early-diagnosed patients and perform the silencing experiments. In the last 2 months we will perform the RNA-seq and data analysis.

Posted in ECCO News, Committee News, SciCom, Fellowships & Grants Synopsis Reports, Volume 13, Issue 4