The objective of DISSECT-HF is to generate engineered heart tissue (EHT) with the use of human induced pluripotent stem cells (hiPSC) from specific forms of heart failure (HF). It focusses on three etiologies of HF with a clear trigger and a large inter-individual susceptibility (pregnancy induced HF, anthracycline cardiotoxicity and PLN cardiomyopathy) to unravel common pathophysiological mechanisms involved in the development of HF. The rationale is: - Better understanding of molecular pathways leading to HF and knowledge about inter-individual susceptibility is needed to improve treatment. - For detection of changes on a molecular level cardiac tissue is needed. - Using innovative experimental approaches, such as dynamic loaded EHT (dyn-EHT), patient specific cells, unbiased target finding and deep phenotyping, I will dissect common disease pathways in the development of HF. SPECIFIC OBJECTIVES: 1. Construction of dyn-EHT from patient specific hiPSC derived cardiomyocytes, endothelial cells and fibroblasts. 2. Generation and deep-phenotyping of dyn-EHT from: A) Females with pregnancy induced HF (susceptible) and siblings with a normal pregnancy (resilience) B) Cancer patients with severe HF after anthracyclines (susceptibility) and patients who could resist high dose anthracyclines (resilience) C) Patients with an early PLN cardiomyopathy phenotype (susceptible) versus elderly asymptomatic PLN mutation carriers (resilience) 3. Identify overlapping and diverse factors. 4. Validate discoveries and apply in unique human cohorts with data on incident HF. WORKPACKAGES: WP1: Optimize construction of dyn-EHT from patient specific hiPSC. WP2: Phenotyping of dyn-EHT from the three HF etiologies focussing on susceptibility and resilience. WP3: Explore the transcriptome and proteome and apply a systems biology approach. WP4: Validate results and explore human relevance in a large cohort with unique phenotyping.

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.

Reliability and radiation damage issues have a long and important history in the domain of satellites and space missions. Qualification standards were established and expertise was built up in space agencies (ESA), supporting institutes and organizations (CNES, DLR, etc.) as well as universities and specialized companies. During recent years, radiation concerns are gaining attention also in aviation, automotive, medical and other industrial sectors due to the growing ubiquity and complexity of electronic systems and their increased radiation sensitivity owing to technology scaling. This raises the demand for dedicated design and qualification guidelines, as well as associated technical expertise. Addressing open questions linked to respective qualification requirements, the proposed training network “RADiation and Reliability Challenges for Electronics used in Space, Aviation, Ground and Accelerators” (RADSAGA) will for the first time bring together industry, universities, laboratories and test-facilities in order to innovate and train young scientists and engineers in all aspects related to electronics exposed to radiation. The expertise of the space and avionics sectors will be complemented with new and unique test facilities, design and qualification methodologies of the accelerator sector, promising for other application areas. Driven by the industrial needs, the students will be trained by established specialists in all required skills, and acquire expertise through innovative scientific projects, allowing to: (i) push the scientific frontier in design, testing and qualification of complex electronic systems for mixed field radiation environments (ii) establish related courses to train future engineers/physicists; and (iii) issue design and test guidelines to support industry in the field, protecting European competitiveness when radiation effects become as important as thermal or mechanical constraints for the aviation, automotive and other industrial sectors.