Partner 1 : AVENIR team “Gut microbiota and Immunity”, INSERM U1057 / UMR CNRS 7203, Université Pierre et Marie Curie, Paris, France (Harry SOKOL) - Project Coordinator

The coordinator partner laboratory has been created in January 2013 following the highly selective ATIP-AVENIR INSERM program. It is inserted in the INSERM Lab U1057 (UMR CNRS 7203). Partner 1 focuses on deciphering the relationship between the gut microbiota and the intestinal immune system in health and diseases, with a specific interest in inflammatory bowel diseases. Partner 1, along with partner 3 has been involved in pioneer studies which led to the discovery of the IBD-associated dysbiosis and its functional consequences. Partner 1, along with partner 3 has notably pointed out the anti-inflammatory effects of Faecalibacterium prausnitzii that is a bacterium lacking in IBD patients’ microbiota.

Partner 1 is tightly connected to the Gastroenterology department of the Saint Antoine Hospital (AP-HP, Paris) which has an internationally recognized expertise in inflammatory bowel disease field. Actually, the Saint Antoine Hospital IBD patients’ cohort is the larger in France (and one of the larger in Europe) and has initiated major breakthrough in IBD epidemiology and therapeutic strategy in the last 20 years. This connection warrant access to human clinical samples if required, as a biobank (encompassing samples from microbiota and from host) attached to the clinical unit has been recently created and contains already several hundreds of samples.

​Partner 2 : INSERM U1019 / UMR CNRS 8204 Université Lille Nord de France, Institut Pasteur Lille, Lille, France (Mathias CHAMAILLARD)

This team has been evaluated at the highest rank A+ by the national agency AERES in 2009.

The scientific objective of Partner 1 is to decipher the biology of a recently described cytosolic surveillance mechanism, the NODs-like receptors, in human inflammatory and infectious disorders. Within the campus of the Institut Pasteur de Lille, the host team is part of the recently created Inserm/CNRS/Université Lille 2/Institut Pasteur de Lille centers, namely the “Center for Infection and Immunity of Lille” (CIIL) headed by Professor Camille Locht (www.ciil.fr). Notably, CIIL gathers complementary expertise, covering a wide range of disciplines from epidemiology, over molecular and cellular virology, bacteriology and parasitology, to the immunological basis of infectious and non-infectious diseases and translation into clinical applications. The CIIL is hosting about 200 scientists, students and technicians that are structured in 11 research teams, including Partner 1 and Partner 3. In addition, the CIIL hosts two IBiSA platforms of excellence on Imagery, namely Bicel, and on Transcriptomics and Applied Genomics, namely LIGAN. The Chamaillard’s laboratory is housed on the third floor of the Guérin’s building at the Institut Pasteur de Lille. The laboratory consists of about 810 square feet fully equipped facility for cellular and molecular biology work, including a L2 facility.

Partner 3 : Laboratory of Commensals and Probiotics-Host Interactions (acronym: ProbiHote), MICALIS Institute, INRA Jouy-en-Josas, France (Philippe LANGELLA).

Philippe Langella has created his laboratory in 2004 and in less than ten years, this lab is considered now as a reference in the domain of commensals and probiotics-host interactions with many academic and industrial partners. His lab “ProbiHote” is hosting more than 30 scientists, trainees and technical personals. Through this activity, P. Langella is used to coordinate scientific initiatives, managing both scientific projects and human resources.

The Lab is mainly focused on the cross-talk between commensal and probiotic bacteria and the host gastro-intestinal tract in physiological and pathological situations. The skills of this team include expertise in intestinal eukaryotic cell biology, analysis of bacteria-host interactions at the epithelial and immune level and in vivo assay performed on conventional and gnotobiotic animals (in ANAXEM Germ-Free animal platform of the MICALIS Institute). The team has already strong expertise in microbiology which will guarantee good interactions with the other partners of the project. This team will be in charge of the study of the host response at the epithelial level and in charge with partners 1 and 3 of experiments in animal models.

​Partner 4 : Immunologie – Immunopathologie - Immunothérapie - UPMC, U959 Inserm, FRE3632 – CERVI - Hôpital Pitié-Salpêtrière, Paris, France (David KLATZMANN, Adrien SIX)

The “Immunology – Immunopathology – Immunotherapy” laboratory has a unique expertise in translational research in immunology, from bench to bedside. Over the past years, it has engaged in systems biology approaches, towards better understanding of immunopathologies and rational development of immunotherapies. In particular, the “Integrative Immunology” team (i2), headed by Prof. A. Six, was created from pluridisciplinary competences, to implement systems immunology approaches and analysis of the complex organization of the immune system.

i2 has produced:(i) Multi-scale statistical model of lymphocyte repertoire, dynamics and diversity during aging in mice; (ii) Computer modeling (GOAML, copyright UPMC) to simulate lymphocyte dynamics and complex mathematical model using Visual languages, oriented object and finite state machine; (iii) Patented ISEApeaks® technology & software to investigate repertoire diversity and perturbations in a number of physiopathological situations, (e.g. parasite and virus infections, lymphocyte differentiation, humanized mice…); (iv) Original Transcriptome signature discovery: early response signatures of vaccine/gene therapy candidate efficacy (CompuVac & Clinigene FP6 projects) was discovered based on Independent Component Analysis and Gene Set Enrichment Analysis; (v) Database implementation (Gevads  FP6 project, SIDR project). i2 therefore possesses the expertise and competence in bioinformatics and statistical modeling requested, in coordination with the other CombInnate Partners.