The European Rare Diseases Research Alliance (ERDERA) aims to improve the health and well-being of the 30 million people living with a rare disease in Europe, by making Europe a world leader in Rare Disease (RD) research and innovation, to support concrete health benefits to rare disease patients, through better prevention, diagnosis and treatment. This Partnership will deliver a RD ecosystem that builds on the successes of previous programmes by supporting robust patient need-led research, developing new diagnostic methods and pathways, spearheading the digital transformational change connecting the dots between care, patient data and research, while ensuring strong alignment of strategies in RD research across countries and regions. Structuring goal-oriented public-private collaborations targeted at interventions all along the R&D value chain will ensure that the journey from knowledge to patient impact is expedited, thereby optimising EU innovation potential in RD. To support its ambition and missions ERDERA has been designed as a comprehensive and integrated ecosystem of which structure can be compared to an institute encompassing three main parts: (i) funding, (ii) internal (in house) Clinical Research Network that implements research activities targeting clinical trial readiness of RDs and accelerating diagnosis and translation of research discovery into improved patient care, and (iii) related supporting services (Data, Expertise, Education and Training) as well as an acceleration hub that serve external and internal RD community, all supported by all-embracing coordination and strategy and foundational (inter)national alignment.

During tumour development there is a bi-directional communication between cancer cells and immune cells; the process termed tumour immune editing. The impact is reciprocal, shaping both the visibility and susceptibility of the tumour to immune eradication as well as the ability of the immune effector cells to recognise and launch an immune response against tumour cells. Death ligand-death receptor signalling is a key mechanism to kill tumour cells during the early stages of tumour development (tumour immune surveillance). However, the role of this signalling pathway in evolved tumours is poorly understood. Recent pioneering results from DISCOVER consortium members highlighted non-canonical signal tranduction pathways mediated by death receptors, which regulates both tumour cell behaviour (motility, invasion) and effector immune cell function in the tumour microenvironment. The aim of the DISCOVER proposal is to bring a collaborative research network together to determine the role of death ligand-death receptor signalling in tumour - immune cell interactions. The DISCOVER programme will determine how non-canonical signal transduction pathways driven by death receptors control effector immnue cell functions and tumour cell behaviour. The outputs of the research will be used to develop informed therapeutic strategies to interfere with non-canonical death receptor signalling in order to re-activate anti-tumour immune attack and sensitise tumour cells to this attack. The DISCOVER proposal will integrate the research activity of seven beneficiary organisations from 5 European countries, including 3 companies and create a framework for knowledge and reagent exchange for early stage and experienced researchers. The consortium will bring together scientists from immunology and cancer cell biology and combines these with expertise in systems biology, drug discovery and pre-clinical drug development thus forging a consortium where scientific discoveries drive innovation.

Treatments that minimize adverse effects on deep tissues may be critical for successful therapy in a superficial pre-cancerous condition such as Barrett's oesophagus. Although endoscopic therapeutic interventions efficiently eradicate superficial abnormal tissues in the oesophagus, the main challenge with their current deployments is that the therapy depth typically has a more profound thermal injury than the target layer. The project's objective is to develop a novel endoscopic cap that provides local non-thermal ablation to the superficial layers of the target oesophageal wall with sufficient depth for mucosal resurfacing. A design compatible with endoscopes will enable navigation, diagnosis, and ablation together—all-in-one. In support of the objective, the research programme is split into the following indicative specific aims based on EU MDR (2017/745) ISO (13485) & TSE (60601) regulations. Aim-1: Development of numerical modelling to mimic non-thermal ablation dynamics of the endo-cap. Aim-2: Optimization of numerical modelling with computational accuracy by in-vitro studies. Aim-3: Establishing the quality control process. Aim-4: Configuration of the endo-cap's original design in a CAD program and then realize the design with an optically transparent material containing electrodes for a porcine animal model, in vivo. Aim-5: Integration of the endo-cap with an endoscopy system to construct an endoscope equipped with the endo-cap for preclinical trials. Aim-6: Investigating the functional feasibility of an endoscope system in a GI endoscopy simulator. Aim-7: Validation of the system's oesophageal mucosal resurfacing performance in an in vivo porcine model, including tissue samples for histology examination at different time points. The action results are thought to mature the original design sufficiently for clinical trials and provide further steps for introducing the oesophageal mucosal resurfacing technique using non-thermal ablation into clinical routine.

Although diseases afflicting less than 1 person in 2000 are defined as rare diseases, the approx. 6000 different rare diseases together cause, nonetheless, a major burden on human wellbeing and the health systems. Over 90% of all rare diseases are currently without approved treatment and approx. 80% of them are genetic in origin. However, the research on rare diseases and the development of new diagnostic and therapeutic approaches is often hampered by limited resources, including patient material and biological models. The frequency of rare diseases increases in populations with a high frequency of consanguineous marriages. Within ERA, Turkey has the highest rate of consanguineous marriages and, consequently, rare diseases are about twice as prevalent in Turkey than in other ERA countries. The aim of this RareBoost project is to attract an internationally recognized rare disease expert (ERA Chair holder) to the Izmir Biomedicine and Genome Center (IBG), where s/he will lead and direct the new Unit for Rare Diseases and guide its development towards an internationally recognized research facility for rare diseases. IBG is perfectly suited for this development, as it is (i) the largest and best-equipped public biomedical research institute in Turkey, (ii) the only nationally recognized Centre of Excellence in the biomedical sciences, and (iii) already made significant steps towards research excellence. This RareBoost project will greatly facilitate IBG’s aim to become a leading basic and translational research centre for rare diseases. Furthermore, by becoming an internationally recognized hub for rare disease research, IBG will act as a guide for the Turkish R&D sector, will facilitate ERA homogeneity and will support the well-being of rare disease patients. Therefore, RareBoost will greatly boost IBG’s ability to increase ERA-wide cohesion, to support innovation for diagnostics and therapies of certain rare diseases, and to reduce patient suffering.

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial chronic inflammatory disease that is prevalent in 1 of 4 individuals with a significant personal, socioeconomic and healthcare burden, especially at the later, more severe inflammatory stage of disease - non-alcoholic steatohepatitis (NASH). Despite the severe negative impact of the disease on society, NAFLD remains difficult to diagnose and treat. Additionally, the molecular mechanisms underlying the transition from health to fatty liver to NASH remain poorly understood due to the lack of models that faithfully reflect the complexity of human disease. Hence, Halt-RONIN aims to uncover the early triggers of disease initiation and complex mechanistic drivers of disease progression by implementing a systems biology approach with integrative disease modelling resulting in opportunities for the improvement of the existing detection methods, providing a blueprint to inform personalized intervention strategies and drug discovery for NAFLD. To achieve this goal, Halt-RONIN will combine experimental data from advanced in vitro and in vivo models with multimodal data from extensive human NAFLD cohorts and biobanks and use in silico machine learning approaches, to discover new biomarkers and molecular targets specific to each stage of the health-to-disease transition. By validating preclinical experimental findings with real-world data, RONIN will allow for the discovery of novel biomarkers and molecular targets that are specific to the individual patient’s pathology. Consequently, healthcare professionals will gain the tools and knowledge required to diagnose and establish guidelines for the prevention and treatment of inflammation-driven health to disease. As such, in the long-term RONIN will decrease the number of NAFL patients who progress into NASH and provide disease-modifying strategies to improve patient outcomes.