L'Agence nationale de la recherche Des projets pour la science

Investissements d'avenirProjets financés


GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE (MILIEU INTERIEUR)


Action : Laboratoires d'excellence


N° de convention : 10-LABX-0069

Informations générales

  • Référence projet : 10-LABX-0069
  • RST : Luis QUINTANA-MURCI
  • Etablissement Coordinateur : Institut Pasteur
  • Région du projet : Île-de-France
  • Discipline : 5 - Bio Med
  • Aide allouée : 15 000 000 €
  • Date de début du projet : 13/04/2011
  • Date de fin du projet : 12/12/2019
  • Site web du projet : http://www.milieuinterieur.fr/fr
  • Mots clés : Health; immune system; genetic variability; heterogeneity; reference-based population; immune phenotypes; genotype-to-phenotype association; immune profiling; cell population; proteomics; transcriptomics; Host genetics; epigenetics; DNA methylation; pathogens; immune response; infection; mutations; genome-wide association study; whole-genome sequencing; genome-wide SNP genotyping; cohort statistical power; genome coverage; sample size linear regression models; eQTLs; cellular pathway; systems bi

Résumé du projet

While the immune system is highly complex, and its responses are known to considerably vary across individuals and populations, medical practices and public health policies remain based on a single model of patient care and drug development. The Milieu Intérieur (MI) project was initiated specifically to address this discrepancy. Our primary objective is to establish the boundaries of a “healthy” immune response and to define the determinants of immune response variation, integrating the relationship among genetics, epigenetics, lifestyle, and the environment. Phases 1 (foundation) and 2 (consolidation) of the project are now completed, including validation of whole blood immune stimulation assays (TruCulture® technology); design of a clinical protocol and recruitment of 1,000 healthy individuals stratified by age and gender; constitution of a sample bank of whole blood culture supernatants, RNA from stimulated cells, genomic DNA, fecal samples, nasal swabs and punch biopsies across the whole cohort. The cytometry data sets have been generated and analyzed. For all 1,000 donors, whole-genome genotyping data and DNA methylation profiles have been generated. With respect to induced immune datasets, subsets of the cohort have been profiled for proteomic and transcriptomics analysis, and selected stimuli have been characterized. The integration of these datasets is the main goal of phase3 (ongoing), which aims to provide novel insights into the mechanisms underlying genotype-phenotype correlations. Several teams are conducting disease-cohort studies, applying the tools and knowledge generated by our consortium, to disease settings as part of phase 4 (association studies in disease). The MI project is poised to have a strong impact on public health. The MI constitutes a de novo research program, and a true “investment in the future of science” as the scientific output has established a data warehouse and a foundation for integrative research and personalized medicine.

(L'auteur de ce résumé est le coordinateur du projet, qui est responsable du contenu de ce résumé. L'ANR décline par conséquent toute responsabilité quant à son contenu.)