The stated goal of RHAPSODY is to define a molecular taxonomy of type 2 diabetes mellitus (T2D) that will support patient segmentation, inform clinical trial design, and the establishment of regulatory paths for the adoption of novel strategies for diabetes prevention and treatment. To address these goals, RHAPSODY will bring together prominent European experts, including the leaders of the diabetes-relevant IMI1 projects to identify, validate and characterize causal biomarkers for T2D subtypes and progression. Our plans are built upon: (a) access to large European cohorts with comprehensive genetic analyses and rich longitudinal clinical and biochemical data and samples; (b) detailed multi-omic maps of key T2D-relevant tissues and organs; (c) large expertise in the development and use of novel genetic, epigenetic, biochemical and physiological experimental approaches; (d) the ability to combine existing and novel data sets through effective data federation and use of these datasets in systems biology approaches towards precision medicine; and (e) expertise in regulatory approval, health economics and patient engagement. These activities will lead to the discovery of novel biomarkers for improved T2D taxonomy, to support development of pharmaceutical activities, and for use in precision medicine to improve health in Europe and worldwide.

The worldwide prevalence of Gestational Diabetes Mellitus (GDM) has increased steadily over the last decade, affecting up to 10.8 % of the pregnancies in France, mainly due to the rising proportion of women with pre-pregnancy overweight, sedentary lifestyle and advanced maternal age at birth. GDM fuels the type 2 diabetes (T2D) epidemic in the next generation. Whether nutritional interventions during critical time windows in early life, such as breastfeeding could mitigate this risk remains to be explored. Indeed, despite emerging evidence of the infant-health benefit of breastfeeding in GDM, there is still a paucity of data concerning GDM-breast milk (BM) composition in regard with consensual key regulators of energy homeostasis and insulin sensitivity. In original studies, GDM-MILK consortium reported adaptations of BM composition in link with maternal diet or physiological status in human cohorts and in a cross-fostering rodent model of programming. Interestingly, in a pilot study conducted on GDM mothers, using comprehensive human BM (HBM) metabolomics/lipidomics analyses, we evidenced a specific GDM-HBM signature. Based on these preliminary data, GDM-MILK plans to (i) achieve the identification and validation of BM bioactive compounds associated with maternal glycaemia in existing human cohorts and integrate compositional and clinical data, (ii) validate the HBM bioactive components in a pre-clinical rodent model of GDM and explore the mechanisms of adaptations of key maternal organs (pancreas-placenta-mammary gland) impacting GDM-milk composition, and (iii) in vivo using cross-fostering, evaluate the functional impact of a cocktail of milk components previously selected by in vitro studies, on the sensitivity/secretion of insulin in the male and female offspring. This project will provide a major breakthrough in the understanding of lactation period as a sustainable intervention that may curb the T2D pandemic in the next generations and also yield the scientific basis for nutritional recommendations for mothers with GDM and their infants. Therefore, GDM-MILK perfectly fits the research axis Translational Health Research.

Asbestos is one of the major occupational carcinogens. The European Union has an extensive history of protecting workers and consumers against asbestos and even adopted a resolution 2012/2065(INI) ‘on asbestos related occupational health threats and prospects for abolishing all existing asbestos’ last year. Although asbestos is banned, it is still massively present in the built environment. Millions of workers & consumers in the EU were, and still are, for many years exposed to asbestos fibres, despite all measures. Inhalation of even very low quantities of asbestos fibres tremendously increases the risk of developing Malignant Mesothelioma (MM). The IARC reported 8.100 MM deaths in 2010 in the EU. Despite all EU actions, MM incidence is still increasing. MM is a highly fatal disease with a poor median survival time from first signs of illness to death around 12 months despite aggressive treatments. To date there is no curative therapy for MM. MM is considered as an extremely therapy-resistant disease. Chemotherapy consisting of a combination of pemetrexed and cisplatin is considered standard of care with a median survival increase of 3 months (9-12 months). The department of pulmonary diseases of the Erasmus MC, Rotterdam, The Netherlands, in collaboration with international partners, have developed a promising personalised immunotherapy for MM with very limited adverse effects. The first clinical results show a considerably prolonged average survival with limited adverse events (24 months, twice as long). The EMA and the FDA granted this therapy Orphan Designation: autologous dendritic cells pulsed with allogeneic tumour cell lysate for the treatment of malignant mesothelioma (EU: 16 January 2014 - EU/3/13/1229; FDA – US: 06 May 2014). The objective for the project is to deliver the scientific & registration package for market approval by the EMA of a novel immuno therapeutic approach to treat MM. This includes the execution of a phase II/III clinical trial.