Over the years, the European Fund for Regional Development (ERDF) and funds from EU’s Recovery and Resilience Facility (RRF) have played a vital role in biomedical research in low-performing EU Member States. The EU investments have empowered promising research labs, spurred scientific advancements, and improved healthcare outcomes. However, in competitive research fields, ERDF/RRF-funded labs face significant challenges. These include major mismatches between regional and European approaches, divergences between Horizon thematic priorities and national/regional smart specialization strategies as well as differences in funds allocated to consortia versus single beneficiaries. The absence of cohesive internationalization strategies, limited training programs and access to skilled personnel, fragmented research endeavors, and budgetary constraints all hinder the development of sustainable research collaborations with leading research institutes.
To address this timely and pressing need, we propose TRIAD, a program that exploits the upstream synergy mode under pathway A to enhance synergism between three ERDF-funded labs in Greece (Garinis lab), Portugal (Azzalin lab) and the Czech Republic (Krejčí lab) with a scientific focus on the functional role of telomeres in health and disease. Telomeres are essential protective caps located at the ends of chromosomes, responsible for maintaining genomic stability. They play a crucial role in safeguarding chromosome ends, preventing them from being recognized as double-stranded DNA breaks. This, in turn, inhibits the activation of the DNA damage response and prevents chromosome fusions. With each cell division, telomeres naturally undergo a progressive shortening process. When telomeres become too short, cells enter replicative senescence or die, thus preventing uncontrolled cell growth - a major hallmark of cancer. However, cellular senescence can also lead to tissue malfunction. Consequently, the maintenance of telomeres intersects with the processes of aging and cancer (Figure 1). This convergence holds significant promise for innovative therapies targeting age-related diseases, including cancer and improving human health.
The three ERDF/RRF beneficiaries have independently demonstrated a firm commitment to research on genome stability and its profound influence on cancer and aging. Based on ERDF funding, the participating labs have been able to consistently demonstrate excellence in distinct domains within the telomere research field, and develop a remarkable level of complementary expertise in research tools, platforms, and approaches that are otherwise unavailable to each other at a regional level. Specifically:
The Garinis lab (www.garinislab.gr) at the University of Crete (UC) employs animal models carrying inborn DNA repair defects as well as tagged versions of protein factors involved in genome maintenance and/or transcription. Leveraging this unique collection of mice, the team aims to delineate the impact of persistent DNA damage on mammalian physiology during aging and the functional role of genome maintenance in telomere structure and function.
The Azzalin group (https://imm.medicina.ulisboa.pt/investigation/laboratories/claus-maria-azzalin-lab/) at the Institute of Molecular Medicine (iMM) employs a comprehensive range of molecular biology, cell biology, and biochemistry assays to understand the protective functions of telomeres, the mechanistic links between telomere dysfunction and pathological conditions, and the involvement of the telomeric long noncoding RNA TERRA in maintaining telomere homeostasis in health and disease.
The Krejčí lab (https://www2.med.muni.cz/lord/) at the Masaryk University (MU) relies on a series of advanced biophysical and biochemical methodologies to dissect the intrinsic functions of homologous recombination (HR) in telomere maintenance and genome stability. In parallel, the team has developed long standing expertise on the molecular interactions and structural changes occurring at the telomeres and associated protein complexes during aging or cancer.
To foster cross-border collaboration, enhance their research, training and innovation capabilities in the dynamic realm of telomere function in health and disease, the research teams at UC, iMM, and MU will establish the following measurable, verifiable and achievable objectives (Obj.) that are summarized below and analyzed in detail in Section 1.3. Methodology:
Obj. 1. Create a comprehensive joint internationalization strategy via cross border collaboration to significantly enhance the research capacity among former ERDF beneficiaries.
Obj. 2. Implement an inclusive training plan for the development of human resources, providing cutting-edge technological training to early-stage researchers, postdoctoral fellows, and scientific staff while also fostering their proficiency in non-scientific skills.
Obj. 3. Increase innovation capacity by forging strategic partnerships with the industry and cultivating an entrepreneurial environment.
Obj. 4. Facilitate access to excellent European research and innovation networks and communities, actively encouraging collaborations, participation in EU-funded programs, and engagement in knowledge-sharing networks.
Obj. 5. Increase competitiveness in research funding and strengthen the reputation of ERDF monobeneficiary research labs in their applications for European and international research funding opportunities.
Obj. 6. Establish competent management and administrative structures capable of addressing fundraising challenges and efficiently overseeing complex scientific projects.
Obj. 7. Enhance the scientific visibility of the participating research laboratories through targeted and impactful dissemination and outreach endeavors.
The proposed project strongly aligns with the specific challenges and scope of the Pathways to Synergies Action outlined in the Widening Participation and Spreading Excellence Horizon Europe Work Program. TRIAD is designed to bolster R&I performance in three underperforming Member States by facilitating the transfer of knowledge, networking activities, and the exchange of best practices between the ERDF beneficiaries as well as with leading international research institutions. TRIAD will also empower the UC, iMM, and MU research teams to strengthen their R&I capacities in the telomere research field, address skill gaps and deficiencies in basic and translational research pipelines, and implement cutting-edge research and management practices. By doing so, TRIAD will effectively tackle the growing disparities in R&I capabilities among ERA countries, which have a detrimental impact on Europe's economic growth and competitiveness.
Importantly, addressing the pivotal role of telomere dysfunction in health and disease as well as the development of evidence-based therapeutic strategies, aligns with the EU Health Policy and Sustainable Development Goal 3 “Good Health and Well-being” aimed at protecting and improving the health of EU citizens. It is also fully consistent with the National Smart Specialisation Policy in Greece (Sector: Biosciences, Health and Medicines), the National Research and Innovation Strategy for Smart Specialisation (ENEI) in Portugal (Sector: Health, Biotechnology and Food) and the National Research and Innovation Strategy for Smart Specialisation of the Czech Republic (Sector: healthcare, advanced medicine); and the Regional Smart Specialisation Policies of Crete, Lisbon and Brno.