Chronic kidney disease (CKD) affects one in ten people worldwide and is often progressive. Progressive CKD not only causes kidney failure, but also premature aging, cardiovascular disease, and loss of quality of life. Currently, progressive CKD can only be diagnosed after irreversible damage to the kidney has already occurred. There is therefore an urgent need for earlier biomarkers. The kidney consists of filters and tubules, but diagnosis of progressive CKD is currently based on filter function alone. This is surprising, as it is tubular injury that drives CKD progression, and it is the tubule that is targeted by recently developed kidney-protective treatments. U-Tube therefore aims to identify and apply next-generation biomarkers for kidney tubular function to facilitate the early detection and treatment of progressive CKD. My central hypothesis is that the factors that cause tubular injury and CKD progression, are present in urine and therefore detectable as biomarkers. I will focus on urinary microcrystals and extracellular vesicles (EVs) as the drivers of tubular injury, which I will first study in tubuloids using a multi-omics approach. Subsequently, I will perform a large-scale analysis of crystallization and EVs in urine samples from people with stable or progressive CKD. I will then single out those biomarkers that can be targeted by kidney-protective treatment. These targetable biomarkers will be moved forward for the development of a high-throughput tubular panel that I will test for its potential to predict progressive CKD, compared to a gold standard test for tubular function. U-Tube will use cutting-edge innovations to identify urinary biomarkers for tubular function that are targetable and implementable in clinical practice. If successful, it will advance the prediction of CKD progression, and as such redefine how we assess kidney health. By enabling early kidney-protective treatment, U-Tube has the potential to vastly improve CKD outcomes.

Rapid progress in information and biotechnologies offers the promise of better, personalized health strategies using rich phenotypic, environmental and molecular (omics) profiles of every individual. To capitalize on this great promise, key challenge is to relate these profiles to health and disease while accounting for high diversity in individuals, populations and environments. Both Europe and Canada have long-term investments in population-based prospective cohort studies providing essential longitudinal data. These data must be analysed in unison to reach statistical power, however, presently cohort data repositories are scattered, hard to search and integrate, and data protection and governance rules discourage central pooling. EUCAN-Connect will enable large-scale integrated cohort data analysis for personalized and preventive healthcare across EU and Canada. This will be based on an open, scalable data platform for cohorts, researchers and networks, incorporating FAIR principles (Findable, Accessible, Interoperable, Reusable) for optimal reuse of existing data, and building on maturing federated technologies, with sensitive data kept locally and only results being shared and integrated, in line with key ELSI and governance guidelines. Widespread uptake will be promoted via beyond state-of-the-art research in close collaboration with leading cohort networks, focused on early-life origins of cardio-metabolic, developmental, musculoskeletal and respiratory health and disease impacting human life course. To address challenges of sustainability and curation, we will deliver innovative solutions for distributed, low-cost data harvesting and preservation, community curation/harmonization, privacy protection, open source bioinformatics toolbox development, and international governance. EUCAN-Connect platform and collaborations will be coordinated through BBMRI-ERIC (EU) and Maelstrom Research (Canada) to sustain long-term benefits to science and citizens worldwide.

Glioblastoma (GBM) is the most frequent, aggressive and lethal of all brain tumours. It has a universally fatal prognosis with 85% of patients dying within two years. New treatment options and effective precision medicine therapies are urgently required. This can only be achieved by focused multi-sectoral industry-academia collaborations in newly emerging, innovative research disciplines. GLIOTRAIN will exploit the intractability of GBM to address European applied biomedical research training needs. The ETN, which comprises 9 beneficiaries and 14 partner organisations from 8 countries, will train 15 innovative, creative and entrepreneurial ESRs. The research objective of GLIOTRAIN is to identify novel therapeutic strategies for application in GBM, while implementing state of the art next generation sequencing, systems medicine and integrative multi-omics to unravel disease resistance mechanisms. Research activities incorporate applied systems medicine, integrative multi-omics leveraging state of the art platform technologies, and translational cancer biology implementing the latest clinically relevant models. The consortium brings together leading European and international academics, clinicians, private sector and not-for-profit partners across GBM fields of tumour biology, multi-omics, drug development, clinical research, bioinformatics, computational modelling and systems biology. Thus, GLIOTRAIN will address currently unmet translational research and clinical needs in the GBM field by interrogating innovative therapeutic strategies and improving the mechanistic understanding of disease resistance. The GLIOTRAIN ETN addresses current needs in academia and the private sector for researchers that have been trained in an environment that spans translational research, medicine and computational biology, and that can navigate confidently between clinical, academic and private sector environments to progress applied research findings towards improved patient outcomes.