1- Scientific background and objectives The direct access to site-specific natural isotope fractionation provided by high resolution NMR (the SNIF-NMR method) is recognized, not only as a source of selective information in a context of basic research, but also as a powerful technique for controlling the origin of commercial products. However certain limitations have been highlighted: long measurement time; restricted number of accessible molecules because of limited availability, poor solubility or complexity of the NMR spectrum. For the method to be of real use in industrial application, it would be preferable to have shorter analytical times, to be able to test small sample sizes and to have access to a larger range of possibilities in terms of molecular complexity. The aim of this project is to propose a strategy of tracing of the origin of the molecules by generalizing the SNIF NMR approach to other nuclei (in particular carbon-13). The extension of the SNIF-NMR method to other nuclei than deuterium presents two major interests: (i) an increase in the parameters allowing the determination of the molecule finger-print; (ii) the possibility of analysing molecules for which 2H-NMR is particularly difficult or even impossible. 2- Description of project, methodology Two main difficulties are encountered in quantitative 13C-NMR for isotopic measurement purposes: (i) the Nuclear Overhauser Effect and the partial saturation should be eliminated leading to long experimental time and (ii) the variation of the 13C content is small in natural products (~ 5 %) compared to the scale of 2H deviation (~ 50 %). To appreciate such small variations in 13C/12C ratios, analytical methods must be very sensitive, accurate and precise (1 ‰). The global SNIF-NMR approach imposes therefore methodological developments in order to reduce the experimental time and to allow an analysis in a time compatible with an industrial application and without reduction of the accuracy and the precision. Methodological developments, and their validation, are thus essential. The scientific objectives of this project are thus: • Development of a fast protocol for an NMR measurement with very high precision and accuracy: coupling of sequences of magnetization transfer with the ERETIC method will allow a repetition time of the order of the proton T1. The time of acquisition of a quantitative 13C-NMR spectrum could therefore be brought back to approximately one minute without reduction of the accuracy or the precision. • Validation of the multi-nuclei SNIF-NMR approach on a target compound and comparison with the standard protocol (SNIF-NMR-2H and Isotopic Ratio Mass Spectroscopy (IRMS)). • Demonstration of these new and/or optimized tools to detect differences in the synthetic process of pharmaceuticals that could be linked to counterfeiting or patent infringement. 3- Expected results The innovative spin-offs which are expected in this proposal lie in the following scientific originalities: (i) use of lower amount of product, (ii) new contribution of the specific 13C/12C ratios over the global carbon 13 content available by IRMS and (iii) possibilities to establish correlations between the 2H content and 13C content of the same site within the molecule under investigation. Today, the cost of worldwide counterfeiting is evaluated at about 10% of gross domestic product. On this basis, the overall financial loss for France can be estimated at about 13.8 billion €. The development of new methods is a key point in the detection of counterfeiting, to reduce these losses and to protect jobs. Another key point is the respect of new cGMP European regulation that was introduced in October 2005. It is important for the safety of patients to be sure that there is no change in the process or in the suppliers of active pharmaceutical ingredients. This is especially important for generic compounds produced in foreign countries, particularly in Asia, where controls are not easy to organize.

Our aim is to revolutionise the combat against food fraud and enhance transparency in our food supply chains. How? By establishing and mobilising The European Food Fraud Community of Practice (EFF-CoP), a sustainable Research and Innovation eco-system of food fraud researchers and end-users based on solid sociological principles. We have gathered a diverse group of stakeholders in our consortium, scientists, regulators, large and small-sized industry, the organic sector, existing networks with >4200 members, and more to lay the groundwork. They are catalysers to reach out rapidly to a large number of prospective EFF-CoP members. That is only the beginning. We will set out to understand the needs of the various stakeholder groups and the network structure to prioritise content and enhance information flows, and we set up the EFF-Hub as our virtual headquarters, an interactive collaborative space. From there, series of activities will be rolled out – sharing existing research and innovation resources and educational materials, developing new ones – Good Practice Recommendations, factsheets, and case study materials, and we will host engaging virtual and live events to facilitate interactive collaboration. These events involve food fraud festivals, gamification-based training courses, living labs, ‘authentic appetites’ podcast series, the EFF-CoP on Tour program, webinars, virtual cafes, a food fraud incident preparedness workshop, and dedicated events for the future generation. Our goal is to cultivate a vibrant community of over 5000 members at the end of the project, all dedicated to combating food fraud and learning from each other. To ensure our EFF-CoP stands the test of time, we are not only implementing the proven concept of ‘CoP design for evolution’ but also a comprehensive exploitation strategy and business plan. Together we will work towards a future with enhanced authenticity, traceability and transparency within our food supply chains.

Many tropical tree crops are threatened by climate change (CC), including coffee which is highly sensitive to high temperatures, droughts and diseases. 60% of coffee today is cultivated in Agroforestry Systems (AFS), which reduce dependence on external inputs and mitigate the adverse effects of CC. So far, however, breeding has developed cultivars only for open-sun cultivation. Using new Arabica coffee F1 hybrids as a case study, we will design and test coffee varieties, better adapted to AFS and CC and maintaining a robust defense system to biotic and abiotic stresses. By doing so, we will show how breeding programs can benefit both smallholder farmers by improving their incomes, increase the options for sustainability, and benefit the European industry through sustained supplies and a wider range of specialty coffees. The project will take advantage of hybrids, established in 8 countries (Portugal, France, Nicaragua, Costa Rica, French Guyana, Cameroon, El Salvador, Vietnam) under controlled conditions (temperature, light, CO2), field trials and networks of on-farm plots. GxE will be assessed through a multidisciplinary approach where genotypes will be grown in a wide range of environments and low-input management inherent to AFS. Farmers will participate in developing the farm assessment methodology and their experiences with new hybrids (profitability, social acceptance) will inform the breeding strategy. Roasters will be involved in the breeding process through evaluation of beverage quality. By combining extensive phenotyping with metabolomic and transcriptomic analysis, we will develop analytical and predictive tools for Coffee Metabolic Networks, leading to marker aided rapid selection and a new approach for breeding of perennial crops. Impacts will be ensured by innovation platforms, technology transfer for clonal propagation, promotion of direct trading between roasters and farmers, and promotion of new hybrids adapted to AFS.

The world faces a major challenge with the sharp increase in demand for meat and fish by 2050, to which current modes of production, whether through agriculture, aquaculture or fisheries, cannot be sustained. An innovative solution to this predicted shortage of resources, especially protein, lies in insect production and processing which can provide a serious response, but to date no industrial scale of production of insect-derived products has been reached. The FARMYNG project has this ambition to develop on an industrial and automated scale the breeding and transformation of insects for the production of animal nutrition, with the strong participation of 20 key actors all along the value chain from the feedstock supply to the final insect transformation. FARMYNG will demonstrate a large-scale, first-of-its-kind bio-based value chain producing sustainable, safe and premium feed products from an innovative origin: the Tenebrio molitor insect (mealworm). The plant developed for FARMYNG will use the efficiency of mealworm physiology to convert vegetal by-products in mealworm biomass and transform those mealworms into sustainable proteins and lipids for fish feed and pet food end markets. In parallel, manure will be recovered for soil fertilization applications. Insects are indeed very effective at converting organic matter. Fed with no-noble materials, insects multiply quickly, and are a rich and natural source of food for certain livestock and pet animals, and probably ultimately for the Humans directly. Insects also emit less greenhouse gases and ammonia and use less water and land than other animal proteins value chains. FARMYNG project, responding to the increasing worldwide proteins demand, will transfer the technology from a demo plant to the Industrial Flagship Plant able to produce almost 1 500 tons of proteins and 400 tons of oil per month, reaching a productions rate never demonstrated before for insect’s proteins production plant.