Strengthening french participation in European or international calls is a major challenge. The MRSEI program aims to facilitate access by French scientists to these funding programs by supporting the creation of networks able of successfully responding such calls. The expected outcome is a reinforcement of the French scientists positioning, to increase their visibility to develop and coordinate ambitious international multidisciplinary projects. We identified two H2020 calls (SC1-BHC-03-2018 "Exploiting research results of the human microbiome for personalised prediction and prevention of disease" and SC2/SFS-02-2019 "Healthy livestock gut ecosystem for sustainable production") that INRA can coordinate. Research in metagenomics and epidemiology has delivered knowledge on associations between the microbiome and many diseases. This also allowed identifying host-microbe-interactions and microbiome-mediated potential causalities and disease mechanisms. The challenge of both calls is to define healthy conditions and predict and/or prevent diseases. The Pathom’NET project aims to cover the impacts expected by the selected calls. For SC1-BHC-03-2018, these are to i) develop personalised medicine approaches for the prediction/prevention of diseases through exploitation of existing microbiome and Omics data, ii) identify and validate microbial functionalities for robust healthy conditions, iii) define more valuable clinical tools to iv) predict and prevent diseases. For SFS-02-2019, the gut ecosystems of livestock should be characterized, their functions and interactions (with host, feed…) should be studied in order to improve production and/or health. The expected impacts are to i) improve resource use and environmental impact of livestock production and/or livestock health and ii) increase production efficiency, including reduced losses, and contribute to more resilient production systems. As such objectives cannot be accomplished on an individual country level, both calls expect intensive collaboration and synergies between scientists across disciplines. In accordance with this, we started to build our consortium to cover the aspects required by the calls and reach the expected impacts. The challenge of both calls being to define healthy conditions and predict/prevent diseases, we gather specialists of OMICs data analysis, statistical integration and modeling, together with biologists with specific model systems to validate the hypothesis that will be pinpointed by these approaches. For SC1-BHC-03-2018, the aim is (i) to build on existing high quality databases, and study endogenous and exogenous factors (lifestyle, ageing, diet, environment…) to accelerate the translation into novel and personalised approaches and clinical tools for disease prediction and prevention. These novel clinical means will need to be validated and efficiently integrated into personalised medicine, in line with expected impacts (iv & v). For these aspects, we include epidemiologists and teams involved in clinical approaches. In addition, to identify and validate microbial functionalities for robust healthy conditions (ii), we have partners involved in microbiome analysis, epidemiologists and specialists of the intestinal physiopathology. For SFS-02-2019, the gut ecosystems of livestock should be characterized (comparing species, breeds, production systems, evolution with age, transmission), their functions and interactions with host, feed and management should be studied to improve production and/or health. Again, in line with the expected impact, we gather specialists of multi-OMICs data analysis, statistical integration together with biologists to validate the biomarkers that will be identified. To conclude, our program will allow us to develop the international consortium needed to cover the aspects required by the selected calls and reach all the impacts expected. The pathom’NET project will end with the second H2020 application, April 2019.

The Ebola virus one of the most virulent human pathogens. It induces a generalized haemorrhagic fever with a mortality rate of 25%-90%. Glycoprotein (GP), the unique surface protein and essential for infection, triggers virus attachment to the target cell and viral DNA release into the cytoplasm. The overall objective of this project is to better characterize these viral mechanisms and to obtain neutralizing camelid antibodies targeting key stages of infection. To this end, we will focus our research on obtaining neutralizing antibodies (nanobodies or vHHs) from camelid immunization with the Ebola virus glycoprotein. Nanobodies devoid of light chain have high affinities for their antigens and are easily produced in E. coli. Because infection by Ebola virus is a two-step process, these nanobodies will be assembled in constructions having specificity against the GP in general, for entry into the cell endosome, and against his binding site endosomal fusion site in view to block the release from the endosome. These constructions of neutralizing nanobodies will be tested in vitro and be co-crystallized with the GP in order to improve the binding strength nanobody-GP. Finally, these nanobodies will be used by the partner at the Pasteur Institute to achieve neutralization tests in vitro and by the P4 lab partner in Lyon for mice in vivo tests.