Parkinson's disease (PD) is one of the major degenerative diseases for which there is no cure. There is therefore a pressing need to identify mechanisms implicated in PD pathogenesis that can be targeted for therapy. In this context, LRRK2, one of the major genetic determinants of sporadic and familial forms of MP, has emerged as a promising therapeutic target. Specifically, the importance of LRRK2 phosphorylation for its physiological and pathological functioning has recently become clear. Here, we will study the targeting of LRRK2 phosphorylation in PD models in drosophila, rodent neurons, rodent brains and in human cells. The validation of LRRK2 phosphorylation as a potential therapeutic target will open perspectives to develop modulators of phosphoregulators as candidate therapeutics for PD.

The past three years have witnessed the striking discovery of twisted multilayer graphene as a versatile plateform to realize quantum phases of matter in a controlled setting. Recent experiments have demonstrated tunable superconductivity, correlated insulators and topological phases. These phases emerge from flat bands in Moire twisted profiles and can be explored at low electrical doping. As our understanding of these graphene systems is improving with an intense theoretical and experimental activity, there are still many open questions on the nature of the exotic phases and on how they can be probed experimentally. The aim of our project is to combine progresses in analyzing the rich physics of twisted graphene materials with a more precise understanding of the various experimental probes to distinguish competing phases, detect superconducting order, insulating mechanisms, topological properties or transport regimes.

Pain is one of the most distressing symptoms during the early postoperative period. Pain also occurs when rigid sealants are employed to stick tissues or close wounds as they hurt fragile tissues. To the best of our knowledge there is yet no sealant able to connect tissues in a soft manner. In this context, our project aims to develop original “soft glues” to efficiently connect tissues without mechanical constraints. SoftGlue will be elaborated in a one-step, easy to be scaled-up method, in water, at room temperature and without the need of organic solvents. In vitro studies will be carefully designed to minimize animal experiments, better understand the mechanisms of action of SoftGlue and optimize the formulations. First, in vitro sealing properties of SoftGlue will be assessed and compared to commercial products. Mechanical properties will be characterized using a set of standard procedures. In addition, we will develop an original method to study the bioadhesive properties, using an optical device to visualize SoftGlue in tissues under mechanical stresses (effect of thermo - mechanical solicitations) mimicking in vivo bonding wounds, blood flow, etc. After in vitro evaluations, selected few (3-4) SoftGlue will be evaluated in vivo. Tissue regeneration will be evaluated and neovessels formation will be investigated. Cell proliferation and migration will be assessed. Finally, a detailed diagram of the possible in vitro and in vivo toxic and genotoxic effects will be established. This project is a real opportunity to develop a long-term collaboration between complementary teams and to get this consortium persisting beyond scope of the project. SoftGlue is an ambitious interdisciplinary project dealing with an important societal need.

Humans are microbial, living in close functional interaction with their skin and mucosal microbiomes. Human-microbes interplay has proven essential for the maintenance of health and well-being and profiling of microbiomes will become an essential feature of the personalized preventive nutrition and medicine of tomorrow. Europe has gained a leading position in microbiome science and yet to fulfill societal expectations, an international consensus will be essential on key aspects. These include i) clinical trial design as well as analytical standards, ii) definitions of healthy microbiomes as a function of numerous factors, accounting for confounders, iii) means of demonstrating causality of altered host-microbes interactions in diseases and iv) processes for the development of clinically relevant, validated biomarkers. The International Human Microbiome Concertation and Support Action (IHMCSA) will tackle all necessary steps to open the perspective of managing nutrition and health of the microbial human. Involving key stakeholders representing the multiplicity of actors concerned, including citizens, IHMCSA will map existing material, delineate necessary steps and pathways for innovation and build consensus on priorities and means for the future of microbiome science and its translation. This will lead to recommendations, validated by an international Strategic Steering Committee as well as academies of medicine of the world, directed to the European Commission, international research programmes, funding and regulatory agencies and decision makers of health systems. To ensure sustainability of the proposed measures, IHMCSA will promote unified repositories for sharing standards, SOPs and data, and contribute to the structuration of the European Microbiome Centers Consortium with a role in gathering world microbiome networks of excellence. With IHMCSA, human-associated microbiomes will be recognized for their true value in contributing to secure the future of mankind.

Cardiovascular diseases such as atherosclerosis and its consequences as myocardial infarction are the leading cause of mortality worldwide. Therefore, there is a need for new therapies to reduce atherothrombotic events. Mucosal-associated invariant T (MAIT) cells function at the interface between innate and adaptive immunity. Inasmuch as MAIT cells can produce pro-inflammatory and pro-atherogenic cytokines such as interferon-?, we hypothesize that MAIT cells could play a determinant role in the inflammatory response of atherosclerosis. This proposal will be the first to address the role of MAIT cells in atherosclerosis. This work will involve validated animal models, in combination with cellular mechanistic studies and a clinical translational part addressing the relevance of the experimental findings to human disease. Targeting MAIT cells may constitute an attractive therapeutic strategy to reduce cardiovascular diseases.