Strongly associated with the epidemics of obesity and type 2 diabetes mellitus (T2DM) that are testing healthcare systems worldwide, Non-Alcoholic Fatty Liver Disease (NAFLD) is an increasingly common cause of advanced liver disease in the aging population of Europe. NAFLD is a spectrum of hepatic fat accumulation (steatosis); steatosis plus inflammation (non-alcoholic steatohepatitis, NASH); fibrosis/cirrhosis; and hepatocellular carcinoma in the absence of high alcohol consumption. Up to 30% of the EU population have NAFLD, which will be the main aetiology underlying liver transplants by 2020. However, NAFLD is characterized by substantial inter-patient variability in severity and rate of progression. What determines this is unknown. A large population is at risk, but only some experience morbidity. NAFLD severity is currently best assessed by liver biopsy, an invasive, costly and risky procedure - factors that hinder treatment. There is a need to understand the biological and environmental factors that drive inter-patient variability and to develop robust and more acceptable methods for diagnosis, risk stratification and therapy so that effective medical care may be targeted to those that will benefit most. The overall EPoS concept is that improved understanding of pathogenic processes and drivers of disease progression will best be achieved when multiple ‘omics’ approaches are applied to a single cohort of patients to build a multi-dimensional record of how systems are perturbed across the entire spectrum of disease. NAFLD sits at the intersection of key biological processes: carbohydrate/lipid homeostasis, immune/inflammatory activation, wound healing/fibrosis and cancer biology. Once completed, EPoS promises to deliver a substantial and definitive atlas of pathophysiological variation across a spectrum of progressive liver disease. Translation of these findings will therefore impact on closely related pathologies including T2DM and cardiovascular disease.

Osteoarthritis (OA) is the most common form of arthritis of the joints, affecting over 70 million EU citizens. At present, no cure for OA is available; only symptomatic therapies may help to ameliorate this painful disorder. OA affects the integrity of the cartilage and progresses to an increased damage in its surrounding tissues, inclusive bone, and to inflammation of the synovial tissue. The latter reaction is caused by an accumulation of bone splinters. The therapy of choice would be – if available – bidirectional: first, regeneration of the damaged cartilage (by implants) and second, dissolution of the bone fragments (by injections). This proposal presents for the first time this two-fold solution. Within my ERC Advanced Grant “BIOSILICA” (No. 268476) we disclosed that biosilica elicits morphogenetic activity in cells involved in connective tissue formation. The effect of silica is augmented by another natural inorganic polymer, by polyphosphate (polyP), which is synthesized in most animal cells, especially blood platelets that accumulate in damaged bone and cartilage. polyP acts as “metabolic fuel” for the synthesis of the extracellular inorganic and organic skeletal and cartilage tissues. Our strategy is to combine and to amplify the beneficial properties of these two polymers, biosilica and polyP, their morphogenetic activity with their structure-forming/guiding activity, by applying hybrid microparticles, consisting of silica and polyP. The proposed project will provide the proof-of-concept of this dual strategy, using silica and the amorphous Mg2+/Ca2+ salt of polyP together with hyaluronic acid, to dissolve firstly existing bone splinters in the synovial fluid (by injection), reducing the painful joint burden in osteoarthritis, and secondly to repair damaged cartilage with polyP/silica implants. This innovative material, injectable and implantable, will be developed to commercializable products for the benefit of the aging society.

The UNLIMITED project addresses the critical challenges of lipid immunometabolism, a rapidly emerging field with transformative potential for treating immune-mediated diseases such as cancer, autoimmunity and metabolic disorders. Lipid metabolism has been recently recognized as a regulator of immune cell function, yet the intricate interactions between lipid pathways and immune responses within tissue-specific microenvironments remain poorly understood. This knowledge gap hampers the development of precision therapies tailored to the metabolic needs of immune cells in diverse tissue niches. To tackle these challenges, UNLIMITED will train 15 Doctoral Candidates in cutting-edge interdisciplinary research, equipping them with expertise spanning immunology, bioinformatics, metabolism, and drug development. A key feature of UNLIMITED training programme is the integration of leading-edge methodologies, such as multi-omics machine learning, single-cell technologies, CRISPR-Cas9, and spatial metabolomics, alongside groundbreaking techniques pioneered by consortium partners, including SCENITH, Met-Flow, click-chemistry, LIPSTIC, and advanced lipidomics. UNLIMITED’s training program emphasizes a holistic, interdisciplinary approach, providing DCs with technical skills, unparalleled expertise, and transferable competencies to thrive in academic and industrial sectors. The project will unlock unprecedented insights into how lipid metabolic pathways regulate immune cell function and adapt to changes in the tissue microenvironment. This knowledge will enable the identification of novel therapeutic targets and pioneering precision therapies for immune-related diseases. This bold initiative strengthens Europe’s leadership in health innovation, creating a new generation of highly skilled researchers ready to transform global healthcare and advance therapeutic frontiers.

Cardiovascular diseases are the leading causes of mortality in Europe and worldwide. Currently, synthetic prostheses used in bypass vascular surgery are produced from polyethylene terephthalate [PET] and expanded polytetrafluoroethylene [ePTFE]. Those materials show less than optimal, insufficient biocompatibility and durability properties, especially if used for SMALL DIAMETER BLOOD VESSELS. Within the frame of ERC Advanced Grant “BIOSILICA” (From gene to biomineral: Biosynthesis and application of sponge biosilica; Grant No. 268476), we unexpectedly discovered that distinct natural, biodegradable and biofunctional polymers, including biosilica and inorganic polyphosphate (anionic), are not only bio-printable but also morphogenetically active. Likewise attractive is that those biopolymers can be functionally processed by non-toxic and charged (cationic) linkers with growth/differentiation potencies. Therefore, these formulations, backbone polymers and bioactive linkers, allowed the fabrication of unprecedented “Modular Small Diameter Vascular Grafts (MSDVGs)" which combine in an optimal way physical strength with physiological activity. Furthermore, the fabrication of the synthetic vessels is performed by a home-made, easy to handle, extruder device which has been developed by our group. Therefore, this new ERC-PoC project will provide small diameter (< 6 mm) blood vessel implants (incl. the fabrication device - the extruder) urgently required in clinics, with superior properties and at low-costs, at the end of the project. We are definitively convinced that, in view of their advantages, our vessels will be preferentially used for patients requiring bypass surgery. The experimental data gathered disclose that we have in hand a product with a clear biomedical application potential. Besides of their economical value, our new type of artificial blood vessel will certainly improve the quality of life and well-being of patients with cardiovascular disorders.