Spatially structured chip-based cognition platform for molecular mapping and therapy induced neurocognitive dysfunction modelling in pediatric medulloblastoma.

Objective

SCOPE (Spatially structured Chip-based cOgnition Platform for molecular mapping and thErapy-induced neurocognitive dysfunction modelling in pediatric medulloblastoma) aims to create a human-relevant organoid-on-a-chip system to study how craniospinal irradiation and chemotherapy disrupt neurodevelopment and cognitive function in childhood Group 3 medulloblastoma. Its central objective is to model brain region-specific vulnerabilities to therapy and identify molecular pathways underlying treatment-induced neurotoxicity. The project will integrate induced Pluripotent Stem Cells-derived cerebellar and 3-dimensional bioprinted spinal organoids with tumor spheroids in microfluidic chips engineered for precise spatial and temporal control. This platform will enable real-time mapping of therapy-induced cellular and molecular alterations across cognitive circuits. Spatial proteomic analysis through advanced multiplex imaging will reveal protein-level signatures of neurodevelopmental disruption, while Artificial Intelligence-driven analysis will model spatiotemporal patterns of injury and predict long-term impact on cognition. The combined approach of organoid biology, chip engineering, and computational modeling will generate a multidimensional understanding of therapy-driven changes. SCOPE is fully aligned with the Marie Skłodowska-Curie Actions (MSCA) work program by tackling the urgent challenge of protecting neurocognitive health in pediatric cancer survivors. It will train the fellow in organoid culture, microfluidics, proteomics, imaging, and AI-based systems biology, providing strong interdisciplinary expertise. Beyond advancing mechanistic insights, SCOPE establishes a developmentally relevant preclinical platform that strengthens EU research capacity, supports translational innovation in pediatric oncology, and contributes to reducing treatment-related disability in children surviving brain cancer.