ERA Chair Program to Advance Inflammation Research at IMBB-FORTH

Project Information

InflaCare

Grant agreement ID: 101180309

DOI

10.3030/101180309

EC signature date 31 October 2024

Start date 1 March 2025

End date 28 February 2030

Funded under

• Widening participation and spreading excellence

Total cost

No data

EU contribution

€ 2 500 000,00

Coordinated by

IDRYMA TECHNOLOGIAS KAI EREVNAS
Greece

Periodic Reporting for period 1 - InflaCare (ERA Chair Program to Advance Inflammation Research at IMBB-FORTH)

Reporting period: 2025-03-01 to 2026-05-31

Summary of the context and overall objectives of the project

Inflammation is essential for host defence, but when dysregulated it contributes to autoimmune, neurodegenerative and malignant diseases. Despite its major health burden, key inflammatory mechanisms remain insufficiently understood, limiting the development of precise therapies.

IMBB-FORTH is a leading Greek biomedical research institute with expertise in gene regulation, immunity and molecular medicine. However, like many institutions in EU Widening countries, it faces difficulties in attracting and retaining talent, developing translational research, securing competitive funding and strengthening industry collaboration.

InflaCare addresses these challenges by establishing an ERA Chair in Inflammation Biology led by Prof. Dr Manolis Pasparakis. The project aims to develop an interdisciplinary research programme linking fundamental inflammation biology with translational applications; strengthen human capital through training, mentoring and mobility; improve funding, collaboration and talent retention; promote innovation, intellectual property and industry partnerships; and align research management with European Research Area standards.

Scientifically, InflaCare will investigate inflammatory mechanisms and support the identification of biomarkers and therapeutic targets using genetically engineered mouse models, omics, RNA therapeutics and targeted delivery systems. Institutionally, it will strengthen research management, competitive funding capacity and the sustainable establishment of an inflammation research unit at IMBB.

The project will also contribute to EU health and innovation priorities by supporting new approaches to chronic inflammatory diseases, technology transfer and regional development. At European level, it advances the ERA Chairs objective of reducing research and innovation disparities and strengthening Greece’s participation in the European Research Area.

Overall, InflaCare combines scientific excellence, institutional capacity building and innovation to address unmet medical needs and establish a sustainable model for biomedical research in Widening regions.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During RP1, InflaCare established the scientific and technical basis of an interdisciplinary inflammation research programme at IMBB-FORTH. The ERA Chair holder and multidisciplinary team were integrated, continuous mentoring was implemented, and the programme advanced from planning to active experimentation. Genetically engineered mouse models covering innate immune signalling, nucleic-acid sensing, inflammasome pathways, inflammatory cell death, IL-1 signalling and 5xFAD-associated neuroinflammation were imported and established. Five projects were initiated. Early findings show that ERCC1-deficient CD4 T cells develop enhanced inflammatory and metabolic programmes and worsen experimental autoimmune encephalomyelitis. Tcea1-deficient cells accumulate endogenous dsRNA and stress granules without strong MDA5 or RIG-I activation, suggesting intracellular buffering of dsRNA. Additional studies examine the roles of gasdermins, IL-1-family cytokines, caspase-8 complexes, necroptosis and NF-κB signalling in inflammation and neurodegeneration. Preliminary data indicate GSDME activation in aged 5xFAD brains and predominant GSDMD expression in microglia. Training in animal research, experimental design, regulatory compliance and bioinformatics further strengthened technical capacity. Overall, RP1 delivered the required models, infrastructure, research projects, initial mechanistic findings and a multidisciplinary team, providing the platform for subsequent mechanistic, omics and translational studies.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

During RP1, InflaCare generated preliminary findings and established platforms that may advance understanding of inflammation, although further validation is required.

ERCC1-deficient CD4 T cells accumulated DNA damage yet remained functional, developed enhanced inflammatory and metabolic programmes and aggravated experimental autoimmune encephalomyelitis. Single-cell and metabolic analyses linked genome instability with TH1 differentiation, mitochondrial activity, lipid accumulation and BHLHE40-dependent adaptation, suggesting new therapeutic vulnerabilities.

Tcea1-deficient cells accumulated endogenous double-stranded RNA and formed stress granules without strong MDA5 or RIG-I activation. This suggests that RNA localisation and sequestration may determine whether transcription stress induces inflammation or an adaptive senescence response.

Advanced mouse models are also being used to define the roles of gasdermins, IL-1-family cytokines and distinct caspase-8 complexes in inflammasome signalling, apoptosis, necroptosis and tissue homeostasis. In neuroinflammation models, preliminary findings of GSDME activation in aged 5xFAD brains and predominant GSDMD expression in microglia indicate cell-type-specific roles for inflammatory cell death.

InflaCare is additionally exploring modified mRNA nanoparticles and extracellular vesicles for delivering nucleases that remove inflammatory cytosolic nucleic acids and RNA–DNA hybrids. This approach aims to suppress inflammation at its molecular source and may support future treatments for neuroinflammatory and ageing-associated diseases.

Potential impacts include new targets, biomarkers, disease models and RNA-based therapeutic strategies, together with stronger research and industry collaboration at IMBB-FORTH. Further uptake will require replication, validation in human models, optimisation of delivery and safety, intellectual-property assessment, scalable manufacturing, regulatory studies, GMP-compatible production, industrial partnerships and follow-on financing.