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Genome plasticity and infections

Laurence Arbibe
Team description

The research interests and goals of the team focus on unravelling RNA-based dysfunctions underlying inflammation, with a specific emphasis on inflammatory bowel diseases. We are dedicated to developing new immunotherapeutic targets and approaches to prevent or treat bacterial infection, including those caused by multi-drug and pan resistant strains by identifying bacterial factors interacting with the host inflammatory and immune systems.

Inflammation is at the core of many diseases, from sepsis to cancer and aging. To tackle these challenges, we're delving into the mechanisms behind uncontrolled inflammation.
Inflammatory Bowel Disease serves as our study model. We've introduced a novel idea - RNA-based processes leading to abnormal spliced products, some with pro-inflammatory and aging properties. Understanding how the body protects RNA processes during stress could transform inflammation research and offer potential therapies.
In Inflammatory Bowel Disease, certain bacterial strains like adherent/invasive E. coli (AIEC) trigger flare-ups. Using advanced sequencing, we're uncovering the genomic secrets of AIEC's virulence factors and their link to inflammation, bridging gaps in our understanding.

Our approach also reveals targets for groundbreaking therapies. From mRNA-encoded antibodies to versatile monoclonal antibodies and antibodies combined with antimicrobial peptides, we're opening new doors to treat inflammation and sepsis.

Our team’s objectives are:

  1. Decipher RNA-based mechanisms modulating inflammation: we will unravel RNA metabolic functions of the epigenetic and RNA splicing regulator heterochromatin protein 1 HP1
  2. Unravel AIEC virulence factors underlying IBD inflammatory state: using a mouse of IBD and TnSeq, we will (i) decipher the pathogenic role of the AIEC in IBD and (ii) uncover new potential therapeutic targets.
  3. Develop new approaches to prevent or treat infections including caused by multidrug-resistant bacteria.

In summary, we're unlocking the mysteries of inflammation with IBD as a model. These insights may reshape how we view inflammation and offer novel treatment strategies.

Key publications
Mata-Garrido J, Xiang Y, Chang-Marchand Y, Reisacher C, Ageron E, Guerrera IC, Casafont I, Bruneau A, Cherbuy C, Treton X, Dumay A, Ogier-Denis E, Batsché E, Costallat M, Revêchon G, Eriksson M, Muchardt C, Arbibe L. The Heterochromatin protein 1 is a regulator in RNA splicing precision deficient in ulcerative colitis. Nat Commun. 2022; Nov 18;13(1):6834. doi: 10.1038/s41467-022-34556-3. PMID: 36400769 ; PMCID: PMC9674647.
Pons S, Frapy E, Sereme Y, Gaultier C, Lebreton F, Kropec A, Danilchanka O, Schlemmer L, Schrimpf C, Allain M, Angoulvant F, Lecuyer H, Bonacorsi S, Aschard H, Sokol H, Cywes-Bentley C, Mekalanos JJ, Guillard T, Pier GB, Roux D, Skurnik D. A high-throughput sequencing approach identifies immunotherapeutic targets for bacterial meningitis in neonates. EBioMedicine. 2023; Feb;88:104439. doi: 10.1016/j.ebiom.2023.104439. PMID: 36709579 ; PMCID: PMC9900374.
Meijer BM, Jang SM, Guerrera IC, Chhuon C, Lipecka J, Reisacher C, Baleux F, Sansonetti PJ, Muchardt C, Arbibe L. Threonine eliminylation by bacterial phosphothreonine lyases rapidly causes cross-linking of mitogen-activated protein kinase (MAPK) in live cells. J Biol Chem. 2017; May 12;292(19):7784-7794. doi: 10.1074/jbc.M117.775940. PMID: 28325837 ; PMCID: PMC5427260.
Sereme Y, Schrimpf C, Lefebvre-Wloszczowski E, Agapoff M, Faury H, Chang Marchand Y, Agiron-Ardila E, Panafieu E, Blec F, Coureuil M, Frapy E, Bonacorsi S, Skurnik D. Pre-clinical in vitro and in vivo characterization of a maternal vaccination before conception to protect against severe neonatal infections caused by Escherichia coli K1. BioRxiv. 2022; doi:
Reisacher C, Saifi E, Ageron-Ardila E, Theodor Mallmann R, Klugbauer N, Skurnik D, Arbibe L. . doi: 10.1101/2022.11.28.518194. The human-specific miR-6762-5p is an activator of RhoA GTPase enhancing Shigella flexneri intercellular spreading. BioRxiv. 2022; doi:
Funding and grants