Work Packages
WP1 – Coordination, FAIR-compliant data management, ethics, and DEC
The WP aims to ensure efficient coordination and management, align consortium activities with ethical and EU legal standards, develop a FAIR-compliant data management plan for all research outputs, and implement a “no-harm” policy to address the ethical implications of AI systems in COMBAT.
WP2 – DEVELOP high-throughput and super-resolution tools for virus research
This WP focuses on developing advanced imaging and modeling technologies, including ChipNano for live-cell viral tracking and mQ-Tomo for 3D label-free monitoring of neuroimmunopathogenesis while scaling up immunocompetent brain organoids and iPSCs for DENV studies. It also aims to innovate brain-on-chip technology integrated with mQ-Tomo for real-time imaging and develop a multi-omics biomarker algorithm to capture host response dynamics to DENV pathogenesis.
WP3 – DISCOVER novel antiviral strategies against DENV
This WP aims to optimize the existing DENV entry inhibitors, engineer a monoclonal antibody for durable, broad-spectrum protection, and investigate the mechanism of antibody-dependent enhancement (ADE) using ChipNano nanoscopy. It further seeks to identify novel immune modulators through metabolic model-guided drug discovery and demonstrate synergistic inhibition of viral entry, production, and cytokine storm control in an AG129 mouse model.
WP4 – DISCOVER predictive biomarkers and AI tool for Dengue Severity
This WP aims to identify prognostic biomarkers of DENV severity using clinical cohorts, develop a Consensus Association-based gene/protein network to uncover key host factors driving severe disease and create AI-based predictive tools by integrating patient demographics, clinical data, biomarkers, serotyping, and climate information.
WP5 – EXPLORE neuroinvasive and neuro immunopathogenesis in DENV
This WP evaluates the neuroinvasive and neuroinfective potential of DENV strains using a brain organoid co-culture model, tests the efficacy of entry inhibitors and monoclonal antibodies (mAbs) against ADE-driven neuropathogenesis, and investigates the role of cytokine storms in DENV neuropathogenesis while assessing immunomodulators to mitigate their effects.
WP6 – VALIDATE biomarker and pathogenesis of severe dengue for sustainable translation
This WP aims to validate predictive biomarkers identified in WP4 of DENV severity using clinical cohorts from Southeast Asia, create a virus biobank for antiviral studies, conduct high-throughput multi-omics to identify key host factors and perform antiviral assays.
WP7 – OPTIMIZE the IMPACT
This WP aims to enhance pandemic preparedness in the EU by engaging stakeholders to address DENV readiness and improve response strategies. It focuses on the systematization and integration of COMBAT's scientific advancements and key technologies to ensure their effective dissemination and application in scientific research and healthcare practices. Additionally, the project emphasizes long-term sustainability by developing a plan to support COMBAT's contributions to DENV research and global health security. Finally, efforts will be made to prepare key technologies for market success through market analysis, business planning, and intellectual property protection, ensuring their commercial viability.
WP8 – Ethics requirements
The objective is to ensure compliance with the 'ethics requirements' set out in this work package.
