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Assessing the role of ribosomes and mRNA translation in shaping the inflammatory response

Project description

Insight into the regulation of the inflammatory process

Inflammation is part of the body’s natural process of healing. Following injury or infection, inflammatory cells are attracted to the affected site where they recognise danger signals or microbial patterns and initiate downstream signalling pathways. The entire process leads to the expression of specific genes that aim to resolve inflammation. The EU-funded RiboInflam project is interested to delineate the regulation of the inflammatory process at the post-transcriptional level. Researchers will focus on the role of mRNA translation and ribosomes in the inflammatory response. The work will unveil important aspects of inflammation and potential targets for modulating it.

Objective

Inflammation is a highly regulated process that acts as a first line of defense against pathogens infections. Triggered by cellular pattern recognition receptors (PRRs) that recognize specific microbial components and endogenous or exogenous non-microbial components, activation of inflammation induces a dynamic and coordinated gene expression program that leads to the production of cytokines and chemokines to attract effector cells to the site of infection. Although a robust inflammatory response is required for efficient clearance of pathogens, uncontrolled or prolonged inflammation can lead to inflammatory disorders such as septic shocks or to autoimmune diseases like lupus.
Most studies have focused so far on the transcriptional control of the inflammatory gene expression program. However, post-transcriptional regulatory mechanisms involving mRNA splicing, mRNA decay or translation have also been described to control the inflammatory response. Among these, regulation of mRNA translation allows for rapid and reversible modulation of gene expression but its precise role and control mechanisms in the inflammatory response remain poorly understood.
Using innovative technologies, our project aims at characterizing the role of ribosomes and mRNA translation in regulating the inflammatory response. In particular, we propose to identify the complete set of of ribosome accessory proteins and to determine their role in the context of “specialized ribosomes” with specific regulatory activities. We will also study the cross-talks between ribosomes and other cellular processes such as mRNA decay and uncover the role of mRNA editing in regulating translation during the inflammatory response.
From this work, we expect to identify new regulatory mechanisms that orchestrate inflammation as well as cellular factors that could represent new therapeutic targets for the design of drugs modulating inflammation.

Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2018-STG

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Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 499 720,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 499 720,00

Beneficiaries (1)

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