Fibrosis-related chronic diseases (CDs) are amongst the biggest societal burdens in Europe, with fibrosis being recognised as the main driver of morbidity and mortality. Extracellular matrix (ECM) is a key player in fibrosis, with an excessive accumulation of type I collagen (COL1) being a predominant component of the fibrotic tissue. While the increase in COL1 production is considered a main driver of fibrosis, respective drugs had limited efficacy. New evidence indicates that attenuation of COL1 degradation is highly relevant, contributing to onset and progression of fibrosis. Ambitious early stage researchers (ESRs) will join forces within a multi-disciplinary, comprehensive and inter-sectoral doctorate training programme, embedded in an existing network of excellent research groups across Europe, to investigate the “outside-the-box idea” on impaired COL1 degradation being a key driver of fibrosis. The main scientific goal is to improve the understanding of molecular mechanisms associated with COL1 degradation in major fibrosis-related CDs, and investigate the disruptive hypothesis of attenuated COL1 degradation being the key driver of fibrosis and a major contributor to onset and progression of CDs. This will be achieved through multi-disciplinary research and training combining state-of-the-art –omics approaches and data (peptidomics, proteomics and transcriptomics) in a bioinformatics framework, followed by in- and ex-vivo investigation, complemented with ESRs training on translational skills and competences. Such a programme will train a new generation of translational researchers able to covert ideas into products, and will have a profound impact on their employability, and competitiveness. The project will progress beyond the state of the art and provide the currently missing fundamental knowledge on the molecular pathophysiology of COL1 degradation, setting up the stage for novel biomarkers and anti-fibrotic therapies.

Musculoskeletal pain from diseases such as arthritis and cancer in the bone affects the quality of life of millions and is a major societal burden. The current treatment options are opioids, non-steroid anti-inflammatory drugs and disease modifying drugs; however, these are often insufficient in providing an adequate pain relief. This is due to dose limiting side effects, the risk of misuse and addiction (opioids) and lack of efficacy. Thus, there is a strong unmet medical need. Drug development in pain has been hampered by a poor translation of preclinical data to the clinic and a lack of understanding of the underlying mechanisms. Therefore, in this project 4 academic beneficiaries, 3 industrial beneficiaries, 2 industrial partners and 3 academic partners join forces to create an outstanding and integrated training program for early stages researchers to increase the clinical translation of bone pain research and drug discovery and to provide novel mechanistic insight and potential therapeutic targets. We will develop fully humanized organ-on-a chip models of the painful bone disease microenvironment and we will use humanized mouse models, and tissue and liquid biopsies from patients to obtain clinically relevant data. Moreover, we will identify new disease mechanisms and potential treatment targets and explore the efficacy of clinical stage therapeutics in mouse models of the painful skeletal diseases osteoarthritis, rheumatoid arthritis, cancer in the bone and the rare bone disease, fibrous dysplasia. In an extensive training effort covering both specific research skills and transferable skills, the students will obtain an interdisciplinary, state-of-the-art and innovative training from the participants across sectors. The students will benefit from secondments with industrial partners and with some of the foremost pain researchers in Europe.

The aim is to create an innovative European PhD training network in bone pain. Millions in Europe and beyond suffer from bone pain, a debilitating complication of many musculoskeletal disorders such as arthritis and bone metastasis. However, being a truly multidisciplinary subject spanning neuroscience, bone biology, and even cancer research, it demands a multidisciplinary approach. Despite a huge negative impact on the quality of life of the patients and on society as a whole, no specific treatment is available. To address this societal challenge and the strong innovation potential, we want to form the first European platform to promote frontline research, innovation and education within bone pain. The network encompasses 5 academic and 2 industrial beneficiaries and 1 industrial partner all committed to creating an outstanding wide-ranging yet integrated training program for early stages researchers to elucidate the mechanisms of bone pain and develop new medicines. We will use in vivo models of arthritic pain, cancer-induced bone pain and fracture pain to investigate the pathophysiology and novel treatment strategies. In vivo electrophysiology will be used for studying the physiology and pharmacology of pain transmission and its modulation. Transgenic mouse models will be used to tease out the specific neuronal receptor subtypes involved. Sophisticated behaviour tests will evaluate response to novel treatments. We will create a biobank of human cancer-infiltrated bone to identify specific patterns of neuronal receptor expression and to validate therapeutic targets in humans. In an extensive training effort covering both specific research skills and transferable skills, the students will obtain an interdisciplinary, state-of-the-art and innovative training from the participants, several of which have experience from international networks. The students will benefit from secondments with industrial partners and with some of the foremost pain researchers in Europe

CombiDiag DN aims to develop an AI-data-driven peripheral biomarker based combinatorial diagnostic protocol for early stages of Alzheimers disease (AD), a major form of dementia, and to train a new generation of fellows for this interdisciplinary field. Dementia, a devastating disease of older age, is the challenge of our lifetime and one of the Societal Challenges listed by the UN Sustainable Development Goals and Horizon Europe. CombiDiag responds to this challenge to establish a much-needed DN to carry out an integrated study of minimally invasive and cost-effective peripheral biomarkers, including body fluid markers from blood, urine and saliva, and digital markers from speech, motor functions and sleep for developing the combinatorial early AD diagnostics. The consortium comprises nine academic and eight non-academic institutions across Europe, USA, Canada, and China. It synergises leading academic and industrial experts worldwide to build a triple-i research and training platform for the training of a new generation of Fellows to take early AD diagnostic research to a new level. Fellows will be trained under the Vitae Researcher Development Framework innovatively combined with the CombiDiag platform for triple-i scientific and transferable skills as well as personal quality, creative thinking, and business mind-set. The DN has a highly innovative research programme for the discovery of peripheral AD biomarkers, detection techniques, AI/data driven technology, clinical validation, and integration into trial designs. The advances in CombiDiag research will enable a case finding tool at primary care level for helping achieve improved drug discoveries, disease-modifying treatments, preventive strategies and care provision for AD. CombiDiag will deliver 10 highly-skilled, creative and entrepreneurial Fellows, setting them on a path to successful careers in academia or industry to ensure that the medical and societal challenges imposed by AD are met.