Basic biology as well as applied fields such as agrobiology, biomedicine or biotechnology are undergoing a revolution driven by the realisation that microorganisms impact virtually all biological processes. Microorganisms associated with complex organisms are no longer considered passive passengers but active crews that continuously interact with their host to shape a wide range of biological functions that play a key role in major basic and applied processes. The application of the newest high throughput molecular technologies to address such interplay has given rise to the novel field of hologenomics, which entails the joint analysis of host genomes and microbial metagenomes with the aim of understanding the impact of host-microbiota interactions in basic and applied biological processes. The DN HoloGen has been conceived to lead the development and practical implementation of hologenomics in order to gain a more comprehensive understanding of host-microbiota interactions, and their impact in both basic and applied areas with direct relevance to many of the global societal challenges. We propose to form an unprecedented multidisciplinary and scientifically sound training network by bringing together top researchers with theoretical knowledge on symbiosis biology, microbial ecology, animal evolution, animal production and biomedicine, as well as practical expertise in large- scale (meta)genomics, DNA sequence analysis, metabolomics, computational biology and biological systems modelling. We anticipate that the research results will be (i) of academic relevance through development of new analytical frameworks and understandings of host-microbiome interactions, (ii) of direct relevance to the portfolios of the industrial partners, and (iii) through these portfolios stand to benefit the European Research and Innovation community.

Metabolomics provides a real-time view of the metabolic state of the examined samples. The past decade the field showed strong growth, however limitations intrinsic to the field hinder further application in epidemiology level. Key obstacles include: variety of analyte molecular structures, slow marker identification, large differences in concentrations, poor validation, incomplete combination of data from different analyses and fragmentation of research. The consortium brings together scientists from different complementary disciplines and sectors to collaborate and set a research training network, combining infrastructure experience, knowledge and skills. The research scope is to identify the source of problems that hinder development, and recommend measures to overcome these. Training through research will promote a new generation of omics researchers. Networking, joining forces via secondments will enhance research productivity transfer of knowledge. The project will train 10 ESRs in work-packages aiming toward improvement of design of experiment, harmonization of analytical methods, improved Data Mining and biochemical pathway analysis and translational research. Application will be in the study of blood metabolome of exhaustive physical exercise. We aim to study sample stability & preparation (including blood and alternative forms such as dried blood spots), biomarker identification, exploitation of multiple datasets, promote standard procedures, develop robust pipelines, develop and implement machine searchable notations of metadata, central database for data storage, compare datasets, automate cross-laboratory data combination, develop novel algorithms for multidimensional data mining and reconstruct biochemical pathways. The overall goal is to train the ESRs in cutting edge metabolomics research and at the same time provide proof of concept of democratizing metabolomics by the use of patient centric sampling.

BestTreat fosters education of ESRs in a project to uncover microbiome signatures for risk prediction and monitoring of NAFLD and to contribute to the development of therapeutic treatments based on metabolically beneficial microbial consortia. It trains 15 ESRs at world-leading academic institutions and companies, thus forming strong interdisciplinary links between industry, life and medical sciences, and end-users. BestTreat aims to train a new generation of highly qualified ESRs with entrepreneurial competencies in modern Life Sciences through state-of-the-art research projects. The projects focus on the identification and functional characterization of microbial consortia that contribute to metabolic control, and the application of this knowledge to develop novel leads for drug discovery and therapies for NAFLD. The new field on microbiome based therapeutics requires highly skilled scientists with interdisciplinary knowledge on medicine, systems biology and computer science, as well as hands-on experience with several types of tissue samples and model organisms that can optimally translate their research findings into sustainable improvements in clinical practice. BestTreat overcomes current barriers by establishing a strong, multidisciplinary and inter-sectoral training network, developing technologies tailored to solve key questions in human metabolism, microbiology and bioinformatics. The BestTreat programme will exploit recent developments in high-throughput and genome-wide screening technologies, combine these with modern molecular cell biology and systems biology approaches and ultimately translate the data into new leads for the discovery of live biotherapeutics. This specific cross-disciplinary training program will educate young scientists to the next level needed to advance this research field for the upcoming decennium. The training programme will be complemented with a complete set of transferable skills.

Understanding the interplay between animals and microorganisms associated with them has been recognised as an essential step for improving animal health, welfare and production. To understand the biomolecular interactions that impact production processes, researchers are implementing novel analytical strategies based on studying host genomes, their microbial metagenomes as well as the different ‘omic layers interconnecting them. However, such information, derived from conventional DNA/RNA sequencing and mass spectrometry, does not provide any information about how the different biological elements are spatially distributed in the ecosystem. In consequence, many microbe-microbe and animal-microbe interactions remain hidden due to the lack of resolution of the employed techniques. Acknowledging the three-dimensional (3D) conformation of biomolecules, cells and tissues is now considered a key element for advancing the understanding of biomolecular interactions. In 3D’omics we will develop, optimise and, for the first time, implement this technology in animal production to generate the so-called 3D’omic landscapes, the most accurate reconstructions of intestinal host-microbiota ecosystems ever achieved. Using two terrestrial production systems, namely poultry and swine, we will analyse the effect of a myriad of factors, including animal development, diet, exposure to pathogens and management practices, in the shaping of 3D’omic landscapes. Through coupling our new technology with cutting edge analyses of animal health and performance, we will advance phenotypic variability and genetic evaluations of production animals to a new frontier. We foresee our solution will open new research avenues to improve animal breeding practices, develop microbiota- and host-tailored feeds and animal health treatments, as well as to design new management practices that will enable increasing production efficiency and animal welfare while decreasing the environmental impact.