Cysteinyl leukotrienes (CysLTs) are potent lipid mediators of inflammation. CysLT1 and 2 receptors are widely expressed e.g. lungs, colorectum, heart, brain & eye; and CysLT1 antagonists are prescribed to treat airway inflammation. Excitingly, CysLT signalling was recently discovered to regulate the biology of vascular, neuronal and cancer cells underpinning its untapped therapeutic potential in other diseases. CRYSTAL3 interconnects unique and diverse researchers to create a multidisciplinary team sharing expertise and research capacities. The contribution of CysLT signalling to disease is divulged; its therapeutic potential unlocked and new services & products commercialised. This is delivered by staff exchanges to jointly research Ocular & Central Nervous System (CNS), Cardiovascular system (CV) and Cancer diseases. The R&I goal of CRYSTAL3 is to reduce human disease burden by enhancing EU capability and knowledge-sharing in research and commercialisation. This is achieved through advanced international co-operation between 5 academic and 5 non-academic partners, in 7 countries. The focus is on innovative research into the CysLT signalling pathway in human diseases related to the Ocular-CNS, & CV systems and Cancer (OCCC). The 3 overall objectives of CRYSTAL3 are: A) Combine resources to discover novel pathological mechanisms linking cysteinyl leukotriene signalling to ocular, central nervous system, cardiovascular disease and cancer (OCCC). B) Unite partner capacities to uncover the therapeutic potential of cysteinyl leukotriene signalling in ocular, central nervous system, cardiovascular disease and cancer (OCCC). C) Commercialise products and services co-developed within CRYSTAL3 The CRYSTAL3 consortium tackles these challenges by promoting cross-sector, inter-European R&I staff exchanges among participants with expertise in OCCC disease, computational drug discovery, genetic engineering, pre-clinical disease models, marketing and commercialisation.

The innovative idea behind the EPIPHARM (EPIgenetics of PHARMacogenetics) project is to develop a package demonstrating the feasibility of a high-throughput tool for epigenotyping Cancer of Unknown Primary (CUP) to identify a drug sensitivity fingerprint based in the DNA methylation profile of non-coding RNA (ncRNA) loci. CUPs are a heterogeneous group of cancers defined by the presence of metastatic disease with no identified primary tumor at presentation. The CUP outcome is extremely poor with an expected death within the first six months of the diagnosis. CUP has been reported to comprise approximately 5% of all cancer cases in the world. Despite the introduction of new image technologies and immunohistochemistry methods, more than 50% of CUPs remain anonymous regarding their primary tumor site of origin and, as mentioned, their prognoses are dismal. For most patients with CUP, recommended treatments involves just empiric chemotherapy, usually with a taxane/platinum or gemcitabine/platinum regimens that achieve the described modest clinical benefit. Thus, it is necessary to have better tools to guide the pharmacological treatment of CUP cases. As part of the ERC Advanced Grant “Epigenetic Disruption on Non-Coding RNAs in Human Cancer” (EPINORC) we identified CpG methylation changes in a wide variety of ncRNAs (microRNAs, lincRNAs, T-UCRs, snoRNAs, piRNAs...) that showed a tumor-type specific pattern that has allowed the successful development of the EPICUP assay for the diagnoses of CUPs that it has been licensed and it is undergoing final clinical validation. In the current EPIPHARM Proof of Concept (PoC) proposal, we plan to optimize a ncRNA DNA methylation assay that includes a user-friendly and cost effective approach to improve the therapy of CUP cases by providing a more personalized drug treatment to an extent that will make it interesting commercially for the health providers and their associated company partners.

Severe ocular disorders are affecting the lives of more than 100Mill people world-wide and at least 25% of the population above 70 years of age, a growing demographic group in EU. More than 8 million people lose their lives to cancer every year, making cancer a leading cause of pre-mature mortality in the world. The main hallmarks of severe eye conditions (i.e angiogenesis, inflammation and vascular permeability) play also pivotal roles in cancer, being therapeutic targets to treat both kind of diseases. The overall goal of 3D-NEONET is the improvement of available treatments for cancer and ocular disease by enhancing drug discovery-development and delivery to targeted tissues, through advanced international co-operation between academic and non-academic partners. The interdisciplinary expertise provided by 18 partners in 7 countries encompasses among others: drug screens, ADME, toxicology, preclinical models, nanotechnology, biomaterials and clinical trials. After the success with ongoing FP7-IAPP project 3D-NET (Drug Discovery and Development of Novel Eye Therapeutics; (www.ucd.ie/3dnet), we are assembling 3D-NEONET, this enlarged European interdisciplinary consortium that will join forces and exchange skills to enhance current therapies in oncology and ophthalmology. The 3 global objectives of 3D-NEONET are: 1- Enhance the discovery and development of novel drugs, targets and biomarkers for ophthalmology and oncology. 2- Improve the Delivery of Therapeutics for Oncology and Ophthalmology 3- Enhancement of Research, Commercial and Clinical Trial Project Management Practices in these fields. Through participation in the program, 3D-NEONET is the vehicle for driving synergies between academic and non-academic participants leading to increased scientific and technological excellence as well as tangible innovative outputs that will strengthen the competitiveness of both the researchers and industries of the network even beyond the lifetime of the network.

The EVEREST project is a pioneering consortium in Extracellular Vesicle (EVs) research, bringing together 22 institutions from 11 countries, including 3 UK partners. This interdisciplinary consortium is distinguished by an ambitious plan for over 285 months of staff exchanges, engaging at least 81 fellows. Research-Innovation programme is structured into four pivotal work packages: 1. Combining Expertise and Resources for Advancing Standardised Characterisation and Isolation of EVs: Focused on harmonizing methods for EV isolation across diverse tissues and samples, enhancing the consistency and reliability of EV research. 2. Jointly Investigating EVs in Health or Disease, and Enhancing Translational Biomarker Discovery: Concentrated on exploring the roles of EVs in various health conditions and diseases, with a particular emphasis on identifying and validating new biomarkers for diagnostic and prognostic applications. 3. Uniting Capacities, Advancing EV-Based Therapeutics or Drug Delivery: Dedicated to developing innovative EV-based treatments and drug delivery mechanisms, targeting key health challenges like cancer and cardiovascular diseases. 4. Catalysing commercial development of EV-based technologies: Aiming to bridge the gap between research and practical application, this work package focuses on preparing EV-based solutions for large-scale production and market introduction. At its core, EVEREST is committed to significantly enhancing the capabilities of participating institutions and fostering career advancement for involved fellows. By positioning EVs as critical tools for biomarker discovery and therapeutic applications, the project aims to make substantial contributions to personalized medicine and improved health outcomes, ultimately translating research breakthroughs into clinical practice.

It is the ambition of PRESIST-SEQ to provide a new gold standard in single-cell experimental workflows the cancer research community by developing best practices, standard operating procedures (SOPs), and high-quality FAIR data, with the ultimate aim to empower them to unravel therapeutic resistance. Such, that the community can identify urgently needed markers to predict, prevent, and target tumour resistance. Cancer takes 9.6 million lives each year, 90% of which result from untreatable metastatic relapse occurring after initially (seemingly) effective treatment. Therapeutic resistance is hence a primary cause of cancer death that clinically cannot be predicted, prevented, or treated. Addressing the urgent need for smarter therapeutic strategies is however held back by the lack of standardised experimental approaches that enable studying the biology of residual disease and drug tolerant persister cells in full detail. This need encompasses best practices for single-cell sequencing, advanced modelling techniques using patient-derived organoids and xenografts, and data FAIRification for integrated experiments. To address this need, PERSIST-SEQ brings together globally leading groups in single-cell sequencing technologies, cancer modelling and therapeutic resistance. Furthermore, the consortium has a broad range of clinical samples, cell lines, 3D models (PDX and PDOs) and mice models (GEMMs) at its disposal that can be leveraged to answer a broad range of emerging questions. This positions the consortium excellently to (1) design and standardise single-cell experimental approach to study the biology of therapeutic resistance and (2) initiate the largest single-cell profiling initiative on therapeutic resistance. Importantly, PERSIST-SEQ is organised such that it can quickly adapt to emerging insights and techniques during the project, and that ensures the capture of learnings in manners that stimulate replication of workflows elsewhere.