The Dystrophin Associated Protein Complex (DAPC) is a key actor of the cell – extracellular matrix (ECM) interface, as revealed by its implication in human genetic disorders. However, its molecular and cellular functions are still poorly understood because tractable model systems allowing state-of-the-art in vivo cell biology and genetic approaches are lacking. The three partners of this project have developed the first transgenic dystrophin reporters that have revealed remarkably compartmentalized membrane distributions of the DAPC in epithelia and muscle cells in C. elegans, Drosophila, and mouse. The project aims to elucidate the organization and dynamics of the DAPC and to characterize its new functions in relation to specific cell cortical compartments.

The main target of the Mont-Blanc 3 project "European Scalable and power efficient HPC platform based on low-power embedded technology" is the creation of a new high-end HPC platform (SoC and node) that is able to deliver a new level of performance / energy ratio whilst executing real applications. The technical objectives are: 1. To design a well-balanced architecture and to deliver the design for an ARM based SoC or SoP (System on Package) capable of providing pre-exascale performance when implemented in the time frame of 2019-2020. The predicted performance target must be measured using real HPC applications. 2. To maximise the benefit for HPC applications with new high-performance ARM processors and throughput-oriented compute accelerators designed to work together within the well-balanced architecture . 3. To develop the necessary software ecosystem for the future SoC. This additional objective is important to maximize the impact of the project and make sure that this ARM architecture path will be successful in the market. The project shall build upon the previous Mont-Blanc & Mont-Blanc 2 FP7 projects, with ARM, BSC & Bull being involved in Mont-Blanc 1, 2 and 3 projects. It will adopt a co-design approach to make sure that the hardware and system innovations are readily translated into benefits for HPC applications. This approach shall integrate architecture work (WP3 & 4 - on balanced architecture and computing efficiency) together with a simulation work (to feed and validate the architecture studies ) and work on the needed software ecosystem.

Mitigation of climate change is a key scientific and societal challenge and also a headline target of the EU2020 strategy. Strong reductions in greenhouse gas emissions are necessary to reach the global warming target agreed on at the 2015 United Nations Convention of Parties in Paris. Such emission reductions can only be achieved if sources are properly quantified and mitigation efforts are verified, but there are large discrepancies between official emission inventories and estimates derived from direct measurement of the air. MEMO2 will contribute to the EU2020 targets with a focus on methane (CH4), the second most important greenhouse gas after CO2 and one of Europe’s most important energy sources. CH4 emissions are a major contributor to Europe's global warming impact, but they are also a good target for climate change mitigation because of a rather short lifetime of 10 years (policy-maker compatible) and several sources offering possibilities of “no-regret” emission reduction (landfills, gas leaks, manure). However CH4 emissions are not well quantified yet. MEMO2 will bridge the gap between large-scale scientific estimates from in situ monitoring programs and the 'bottom-up' estimates of emissions from local sources that are used in the national reporting. MEMO2 will identify and evaluate CH4 emissions and support mitigation measures by I) developing new and advanced mobile methane measurements tools and networks, isotopic source identification, and modelling at different scales, and II) educating a new generation of “cross–thinking” scientists, which are able to effectively implement novel measurement and modelling tools in an interdisciplinary and intersectoral context. The 9 beneficiaries and 13 non-academic partners of MEMO2 offer a well–structured intersectoral training programme to equip young researchers with strong scientific and personal competencies, which will enhance their employability as well as European innovation capacity in the future.

Hereditary haemorrhagic telangiectasia (HHT) is a rare disease characterized by epistaxis, mucocutaneous telangiectasia and arteriovenous malformations affecting multiple organs. HHT associates with severe complications such as clotting, bleeding, hypoxia and anemia that can be fatal in 10% of cases. About 80% of HHT patients carry rare coding mutations in ACVRL1, ENG or SMAD4 genes. The partners of this project have recently identified 2 non-coding variations in the 5’UTR of the ENG gene in 2 unrelated HHT patients. These 2 variants are predicted to create upstream AUGs in the 5’UTR in frame with the same stop coding located within the Coding Sequence, thus generating Overlapping Open Reading Frames (uoORF). We found that the 2 newly identified variants were associated with a decrease of the Endoglin protein levels and function in vitro using an assay applied for the first time on non-coding variants. Similar results were obtained on 3 additional uoORF-creating variants in the 5’UTR of ENG previously reported in the literature in HHT patients and considered as pathogenic but with no definitive functional evidence. These findings strongly suggest that the 2 new non-coding variants are HHT-causing. In addition, we conducted preliminary investigations suggesting that the ENG expression could be restored in patients carrying these uoORF-creating variants using a common genome editing approach targeting a specific dinucleotide deletion in the 5’UTR. Based on these results, this project aims at deciphering the exact mechanisms of alteration by uoORFs of the Endoglin protein using molecular tools dedicated to study the mechanism of translation, at ameliorating the molecular diagnosis in HHT by helping variant classification and reducing the number of variants of unknown significance, and at developing new targeted therapeutical strategies based on genome editing and/or antisense oligonucleotide to restore the function of the impaired ENG protein caused by uoORFs.

Due to high critical scarcity for doped semiconductor indium-tin-oxide (ITO), new transparent conducting oxides (TCOs) need to be developed. Recently, new TCOs have been discovered based on strongly correlated electron SrVO3 and CaVO3 phases. These compounds belong to the very rich perovskite family ABO3 (with A: alkaline earth, and B: transition metal) The multiple cationic substitutions at A and/or B sites, can act on the performance of those TCOs such as electronic correlations, bandfilling, … Therefore, in the project DisTCOvery, we have selected some A and B cations, which will be a powerful platform to tune and improve the functional properties (conductivity, transparency) of new perovskite-based TCOs thin films. We will be also able to induce new properties that are absent in other TCOs such as magnetism, which may unlock opportunities for multifunctional devices in the design of next-generation displays and photovoltaics. Finally, we will integrate these new TCOs on glass thanks to 2D nanosheets used as seed layer. Thus, different nanosheets will be developed in line with the different lattice parameters of the TCOs that one wishes to crystallize in order to propose a technological solution for their integration into devices.