Nutrition-Genetics and Environmental Risk Exposure

The N-GERE project:

Our project is based on experimental tools specific to the unit such as, cellular models (chimeric protein with stable expression), animal models (deprived rats and inducible KO mice tgMTR methionine synthase), cohort studies (OASI, Nancy IBD cohort, DANKOPTA, OBESEPI, FEPA, COMET, Spinamet). The unit is member of international consortiums of genetic epidemiology (IBD consortium, I-CARE study, ENDA, etc.) and collaborates with other leading international groups in our fields. The increased number of researchers with HDR in the unit will increase the capacity to supervise new projects by young researchers.

Up to now, the unit harnessed its research activity to the normal and pathological ageing, which is the federative topic of the pole Biology-Medecine-Health (pôle Biologie Médecine Santé, BMS) of the University. Importantly, the orientation of clinical research conforms to findings in experimental models. Our experimental strategy and results led to design hypotheses on innovative treatment thanks to the Bioprolor consortium, FHU Arrimage and FHU PEARL. In this context, we have increased our interactions with the scientific environment notably the hospital of Nancy and the industry, particularly the PAT Company (Bioprolor) and Immupharma (FBU/RHU). We have also developed our collaborative network in the Big Region taking advantage of FHU.

The scientific project of the unit takes into account our recent evolution. It is based on the most relevant scientific results, the introduction of new models and tools of experimental research and clinical research. It also takes into account the strong involvement of the unit in the local, national and international environment, based on the leading role that the unit has played in shaping the FHU ARRIMAGE, the AGIR international call of University of Lorraine on diseased ageing and its involvement in the coordination of a work package of the impact program entitled GEENAGE of Lorraine University of Excellence. Internationally, the unit has taken the initiative to build national and European projects, which, although preselected and well assessed, have not been funded. The main changes that have influenced the frame of the new project are the venue of full Inserm investigators and the capacity of the young academic staff to conduct research programs. We have developed a strong incentive strategy to prepare the HDR for several lecturers and we have benefited from the promotion to PU-PH of several colleagues. Rémi Houlgatte, Inserm research director joined the unit and set up within a research group in Integrative Genomics and Metabolism. David Coelho has been recruited as Inserm senior researcher (CR1) 2 years ago, to develop a project on the pathomechanisms of inherited disorders of the one-carbon metabolism (1-CM). Meanwhile, Laurent Peyrin-Biroulet strongly developed clinical high-level research in the field of inflammatory bowel diseases, while continuing to develop experimental research. These developments contributed to meet the academic capacity to propose a project structured and supported by three teams. This structure in multi-unit teams had not been possible during the previous contract, given the retirement of Inserm researchers and the lack of recruitment.

Team 1 “One-carbon metabolism and epigenomics in developmental origins of inherited and complex diseases” led by Jean-Louis Guéant. The team will dissect genome/epigenome/phenotype relationships by up-to-date “omic” technologies and will investigate pathogenesis of inherited disorders of Cbl metabolism and complex diseases related to foetal programming, using mice, rats and fibroblasts and cohort studies. The team project will be developed in 3 tasks,  « one-carbon metabolism and neurodevelopment », led by Carine Pourié, « pathomechanisms of inherited diseases of the one-carbon metabolism », led by David Coelho and « developmental origins of complex diseases », led by Rosa-Maria Guéant-Rodriguez.

Team 2 “Metabolic-Genomic interactions in personalized medicine of chronic inflammatory bowel diseases” led by Laurent Peyrin-Biroulet. The team will aim to identify new evidenced-based predictors of disease complications and of efficacy and safety of biologics via an in-depth analysis of integrated omic approach to contribute to the development of personalized therapeutics of IBD. The team will also test and develop innovative therapeutic strategies through an integrated pre-clinical and clinical program with European academic and industrial partners bringing unique expertise in the field of chronic inflammatory disorders and thanks to the access to large IBD cohorts and big data.

Team 3 « Metabolism, Integrative genomics & Bioinformatics » led by Rémi Houlgatte and Guillaume Gauchotte. The team will develop a project focused on the integrative genomic mechanisms of carcinogenesis associated with the dysregulations and interactions between genome- epigenome and metabolism. The project is developed in two tasks, “Genomic profiling of lymphoma and lymphoid diseases”, leaded by Remi Houlgatte and “Metabolism, genomics and cancer”, leaded by Guillaume Gauchotte. It will also develop cross-cutting approaches with the other two teams.