While it is known that post-COVID-19-condition (PCC) is caused by SARS-CoV-2 infection, for most other immune-related noncommunicable diseases (IR-NCDs), no such infectious disease (ID) triggers have been identified (yet). Many IDs exist that could potentially cause IR-NCDs, however these microbes have large genomes encoding many antigens possibly associated with IR-NCDs. Given that it is challenging to measure all these 100,000s of structures in parallel, they represent the dark matter of ID-immune interactions. Furthermore, exposure to an ID alone typically does not trigger development of an IR-NCD: For example only a subset of patients infected with SARS-CoV-2 develop PCC. So, genetic- and environmental aspects also affect the onset of IR-NCDs, but the exact factors are unknown for most IR-NCDs. Here, we aim to 1.) identify IDs triggering IR-NCDs by screening for antibody responses against 600,000 ID antigens, and 2.) to disentangle environmental and genetic factors affecting the transition from IDs to IR-NCDs. We will combine novel multi-omics approaches and technologies for personalized genotyping of HLA and adaptive immune receptor genes to deeply profile 6,000 patients of six IR-NCDs (PCC, multiple sclerosis, ME/CFS, rheumatoid arthritis, lupus, IBD) to identify novel biomarkers and disease mechanisms. This project will represent the largest and most deeply profiled systematic study of multiple IR-NCDs with layered datasets allowing for comparative analyses yielding insights into shared mechanisms and potential differences in the role of IDs between IR-NCDs. Building on associations identified from population scale and clinical cohorts, we will demonstrate causality in gnotobiotic mouse models, and leverage machine learning (ML) algorithms to predict disease progression and response to treatment. The combination of novel assays with ML represents a broadly applicable pipeline that can be used for studying the interplay of any other IDs/ IR-NCDs.

Water scarcity, water quality degradation and the loss of freshwater biodiversity are critical environmental challenges worldwide, which have primarily been driven by a significant increase in water withdrawals during the last century. In the coming decades, climate and societal changes are projected to further exacerbate these challenges in many regions around the world. As such, defining a safe operating space (SOS) for water resources in a changing climate and society is urgently needed to ensure a sufficient and reliable supply of water of a quality acceptable for human activity and natural ecosystems. However, defining the SOS for the entire water resources system at spatial scales relevant to decision-making and its projections into the future requires going beyond state-of-the-art water system modelling toward a holistic and participatory assessment framework that includes data gathering, integrated modelling, and working with relevant stakeholders. SOS-Water aims to create the foundation for this framework. It will co-create future scenarios and management pathways with stakeholders in five case studies in Europe and abroad. It will advance water system models and link them with impact models of ecosystem services and biodiversity, to create a novel integrated water modelling system. This integrated water modelling system will be benchmarked against a wide range of state-of-the-art Earth observations and will be used to calculate selected indicators covering all dimensions of water resources systems, to ultimately design a multi-dimensional SOS of policies and water management pathways evaluated across a broad set of scenarios. The results of SOS-Water will help improving the understanding of water resources availability and streamline water planning and management at local to regional levels and beyond, such that the allocation of water among societies, economies, and ecosystems will be economically efficient, socially fair, and resilient to shocks.

The SQUEEZE consortium comprehensively addressed how biomarkers can be used to optimize disease modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis (RA). RA is a chronic immune-mediated disease with enormous health-related quality of life and socioeconomic impact. A broad choice of DMARDs with different targets is up to date available in clinical care, however without sufficient markers indicating the best choice for a particular patient, treatment strategies can be ineffective, cumbersome and expensive. The team of leading academic centres with a first-class record in translational and clinical research, together with patients and small and medium sized enterprises (SMEs) has set out to deliver a collaborative programme to advance the clinical application of biomarkers to improve benefit, safety, and value of approved DMARDs. SQUEEZE utilizes models from data science, clinical trials, translational science, and behavioural science to engage in a complementary, synergistic, and non-overlapping manner addressing the use of biomarkers to improve the ability to select the DMARD with the highest likelihood of fitting the immunophenotypic and clinical profile of the patient, to optimise dose and route of existing DMARDs; and to inform an innovative model of care focusing on patient´s preferences and needs to increase adherence to prescribed drugs. Through nine dedicated work packages SQUEEZE integrates to validate clinical, laboratory, molecular, digital and behavioural biomarkers to enable the recognition of patients with high likelihood of response to treatment and the selection of the drug with highest chance of benefit for an individual patient; and as such improve efficacy and safety of existing therapies (by squeezing the most out of existing drugs) in synergy with other EU-wide activities.

The project NoVOC addresses the Topic Environmentally sustainable processing techniques applied to large scale electrode and cell component manufacturing for Li ion batteries. The activities of NoVOC are tailored to the challenges addressed by the call topic: 1. Lower carbon footprint cell manufacturing in Europe. 2. New sustainable electrode and cell manufacturing techniques with low energy consumption, and no Volatile Organic Compounds (VOCs) emissions. 3. Electrode coating production techniques eliminate organic solvents reduce the capital costs associated to the solvent recovery system. 4. Dry manufacturing techniques with next generation materials. 5. Industrializing closed loops and process design to return low-value chemicals from manufacturing processes to high-value products In NoVOC we aim to design and demonstrate two competitive cell manufacturing technologies aqueous and dry cell manufacturing technologies for automotive batteries intended for production in Europe. The innovations proposed in NoVOC centre on improvements of cell manufacturing process by integrating two novel electrode manufacturing processes into the currently available cell assembly process and demonstrate manufacturability of automotive cells in two formats (pouch and cylindrical) with no toxic organic solvent at the fraction of the cell manufacturing cost that is currently available today. Next generation cell manufacturing processes developed in Europe for electric vehicles batteries

Rheumatoid Arthritis (RA) is the most common, chronic, inflammatory joint disease with a prevalence of about 1% of the adult population (22M patients worldwide and 7M in EU) and estimated to be responsible for 10,000 disability adjusted life years (DALY's) costing EU society €55B annually. Despite aggressive therapy, about a third of patients have to give up work within 5 years of disease onset mainly due to lack of response to multiple disease modifying anti-rheumatic drugs (DMARDs), multi-drug resistance (MDR). Thus, the main objective of this proposal is to define the clinical and molecular phenotypes leading to MDR in RA patients to prevent when possible or, when not possible, optimise the management of these patients. MDR-RA is highly relevant to the program, as these patients are often disabled, unable to work and paying a high personal and societal burden. Moreover, MDR-RA is under-researched and the underlying pathobiological mechanisms for resistance remain unknown, while as we have no predictors of therapeutic response to any of currently available drugs, inevitably treatment is based on trial-and-error. MDR-RA has the ambition of transforming care for these patients and deliver significant advances beyond the state-of-the-art methodologies, as for the first time, molecular pathology will be integrated into clinical, psychosocial, pain perception and imaging profiling in existing clinical cohorts to develop truly holistic predictive models for future clinical use (iCare-RA). The transformative potential of iCare-RA will be tested in a prospective randomised trial in comparison with routine standard of care, while its future implementation potential will be assessed through an early economic modelling. Finally, a strong management and dissemination strategy will facilitate further advancing science in the field, beyond the duration of the project, and future adoption by patients, specialist professional bodies, policy makers and regulatory authorities.