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

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.