Food safety is an important societal challenge in Europe and worldwide. Among the microbial hazards, the presence of Listeria monocytogenes in food is a major concern given the high mortality rate in listeriosis cases, from 15 to 30%. For several years, EFSA has reported an upsurge of listeriosis cases. This phenomenon is worrying, especially since populations at high risk of listeriosis are increasing, particularly the elderly. Indeed, the aging of the European population is leading to an increase of the at-risk populations. Therefore, the objective of this application is to constitute a training network for young researchers. For the past four years, a first H2020 MSCA-ITN-ETN network has allowed us to initiate and consolidate scientific collaborations on the mapping of transcriptional modifications according to the environmental conditions to which bacteria are subjected. The presence of certain compounds in food promotes the expression of virulence factors, which increases the level of virulence of L. monocytogenes after ingestion of the contaminated food. A better risk assessment for the elderly population requires first to focus the research work on the composition of food matrices and the expression of the virulence of L. monocytogenes, and, in the other hand, to take into account the diversity of strains in relation to their habitat. Through the integration of new disciplines into the existing network, the objective of this MRSEI application is to establish the effective structure to integrate the health dimension into the research of food intake and the nutritional status of the elderly population. The establishment of a transdisciplinary network will provide Europe with a training structure adapted to the emergence of a new generation of researchers who can successfully participate in the control of health risks and the nutritional well-being of the elderly.

As the first available prebiotics for neonates, milk oligosaccharides regulate gut microbial composition and modulate host immune response, playing a crucial role in the holobiont assembly. By using two livestock models (pigs and rabbits) with different maturity levels at birth, HoloOLIGO aims to decipher causal links between milk oligosaccharidesstructures, the offspring microbiota and immune system. We will create a database using data mining of the literature to find, visualise and analyse milk oligosaccharidesstructure diversity patterns within and between mammalian species. We will produce the first MO data in rabbits and expand them in pigs. To understand structure importance of milk oligosaccharides, we will undertake in vitro functional analyses in both species on commensal bacterial strains and intestinal immune cells and further validate results in vivo. Finally, we will evaluate, via in silico analyses (pig) and in vivo (rabbit), the existing genetic variability and assess the genetic determinism of milk oligosaccharidescomposition.

Antibiotic resistance is a dramatic health challenge and development of new antibiotics efficient against Gram-negative bacteria of the ESKAPE group is an emergency. In this project, we propose the development of effective first-in-class antibiotics to tackle bacterial resistance by acting on a novel bacterial target, the Mutation Frequency Decline protein (Mfd), and by promoting its inhibition by novel therapeutic molecules. Mfd is a non-essential transcription repair coupling factor conserved in bacteria and absent in eukaryotes. Mfd enables the bacteria to overcome the host defense responses, by conferring resistance to nitric oxide, a major toxic component of the innate immune system. We have identified selective Mfd inhibitors and demonstrated their efficacy against Gram-negative bacteria. Herein, we will optimize these molecules and test their efficacy against bacteria of the ESKAPE group. We will also tackle their pharmacologically challenging properties and develop optimal nanoparticle formulations to ensure their efficient delivery. The originality of our project from a therapeutic perspective is the optimization of compounds that, instead of killing the bacteria responsible for the infection, will block their pathogenic pathways. Targeting Mfd’s function will allow to boost the immune system efficiency and to only focus on bacteria restricted to the inflammation site, thus reducing resistance. This translational project aims to deliver a drug candidate with a solid pre-clinical proof of concept of innocuity to the host and broad range efficacy. As result, a strong therapeutic innovation able to bring an effective healthcare solution to the out-of-control rise of antibiotic resistance will be provided. The complementary and multidisciplinary consortium has already successfully worked together and obtained significant preliminary data, which allow us to be confident about the ultimate success on our challenging project.

Agronomy and biodiversity shall address several major societal, economical, and environmental challenges. However, data are being produced in such big volume and at such high pace, it questions our ability to transform them into knowledge and enable, for instance, translational agriculture i.e., rapidly and efficiently transferring results from agronomy research into the farms (“bench to farmside”). Semantic interoperability enables data integration and fosters new scientific discoveries by exploiting various data acquired from different perspectives and domains. D2KAB’s primary objective is to create a framework to turn agronomy and biodiversity data into –semantically described, interoperable, actionable, open– knowledge, along with investigating scientific methods and tools to exploit this knowledge for applications in science and agriculture. We will adopt an interdisciplinary semantic data science approach that will provide the means –ontologies and linked open data– to produce and exploit FAIR (Findable, Accessible, Interoperable, and Re-usable) data. To do so, we will develop original approaches and algorithms to address the specificities of our domain of interests, but also rely on existing tools and methods. D2KAB involves a multidisciplinary (and international) research consortium of three computer science labs (UM-LIRMM, CNRS-I3S, STANFORD-BMIR), four bioinformatics, biology, agronomy and agriculture labs (INRA-URGI, INRA-MaIAGE, INRA-IATE, IRSTEA-TSCF), two ecology and ecosystems labs (CNRS-CEFE, INRA-URFM), one scientific & technical information unit (INRA-DIST), and one association of agriculture stakeholders (ACTA). The consortium’s expertise ranges from ontologies and metadata, semantic Web, linked data, ontology alignment, knowledge reasoning and extraction, natural language processing to bioinformatics, agronomy, food science, ecosystems, biodiversity and agriculture. The project is structured with three work-packages of research and development in informatics and two work-packages of driving scenarios. WP1 will focus on ontologies/ vocabularies and turn the AgroPortal prototype into a reference platform that addresses the community needs and reaches a high level of quality regarding both content and services offered e.g., SKOS compliance, semantic search over linked data, text annotation, interoperability with other repositories. WP2 will focus on the critical issue of ontology alignment and develop new functionalities and state-of-the-art algorithms in AgroPortal using background knowledge methods validated in ag & biodiv. WP3 will design the methods and tools to reconcile the scenarios' heterogeneous ag & biodiv data sources and turn them into linked data within D2KAB distributed knowledge graph. It will also investigate exploitation of this graph through novel visualization, navigation and search methods. WP4 includes four interdisciplinary research driving scenarios implementing translational agriculture. For instances, an ontology-driven decision support system to select the most appropriate food packaging or an augmented semantic reader for Plant Health Bulletins. We will provide a unique scientific knowledge base for wheat phenotypes and offer the first agricultural data resource empowered by linked open data. WP5 will develop semantic resources for the annotation of ecosystem experiments data and functional biogeography observations. A plant trait-environment-relationships study will be conducted to understand the impacts of climatic changes on vegetation of the Mediterranean Basin. Within a dedicated work-package, we will focus on maximizing the impact of our research. Each of the project driving scenarios will produce concrete outcomes for ag & biodiv scientific communities and stakeholders in agriculture. We have planned multiple dissemination actions and events where we will use our driving scenarios as demonstrators of the potential of semantic technologies in agronomy and biodiversity.

The increasing consumption of fermented foods and beverages is among one of the more notable diet transitions observed in our societies. However, the strong demand for clean label food (rejection of chemical preservatives) and for sustainable agricultural practices (e.g. change towards organic production with low input of fertilizers and pesticides) leads to unforeseen modifications in the quality and safety of these food, especially those made from plant products (vegetables and fruits). Some raw materials are also undergoing biochemical modifications (e.g. in sugar content) due to climate change and increased water stress. These changes in raw materials lead to unexpected modifications in microbial ecology that can be detrimental to the fermentation processes and to the quality of fermented foods and beverages. In this context, the development of generic scientific approaches to help in understanding and anticipating the effects of multiple and complex changes in these productions is a real and urgent need. In addition, solutions to tackle these changes must be sustainable, like the exploitation of taxonomic and functional biodiversity of microorganisms. We will apply an approach of multi-omics-analysis and modelling of the food transformation ecosystems to two typical fermented foods: wine (liquid) and vegetables (solid), for which different challenges exist. These include low-alcohol wine production in a context of climate change, together with organic production and sulphite reduction, and, for various fermented vegetables, addressing health, safety and quality issues in a context of changing production scale (household versus semi-industrial), organic production and salt reduction. The goal of the project is to develop a knowledge-driven approach using synthetic ecology that aims, through the reconstitution of model foods, to predict the behaviour of microbial communities under different constraints. The objective of this strategy is to demonstrate that the production of meta-omics data (gene expressions at the ecosystem scale; global analyses of metabolite production) organized in microbial ecological networks by computational approaches is relevant to anticipate the impacts described above. Furthermore, the project will take advantage of the biodiversity of microbial strains available in partner’s collections for the construction of tailor-made microbial consortia based on the functional properties required to adapt to the expected ecological network changes. Finally, our hypothesis and the solutions obtained on model and simplified foods will be tested at the pilot scale of fermentations of real food to evaluate their validity and the organoleptic and/or nutritional relevance. In a context where fermented foods are at the heart of a societal (food production and healthy nutrition) and environmental (sustainability of production and processes) transition, the results of the METASIMFOOD project will have three major impacts. We will demonstrate the relevance and efficiency of the scientific discipline of synthetic ecology to predict, anticipate and control the behaviour of microbial communities involved in food fermentation processes. Our project will serve as a lever for the deployment of this strategy to other examples of food. It will provide the necessary knowledge base for the development of downstream research programs with industrial partners in the field of fermented foods. Finally, we will ensure a very strong communication towards the general public with an educational and popularization objective.