In vitro modelling of dopamine pathways in fused organoids.

Our group is interested in understanding human brain development in health and disease. A major challenge in the effort to study the biology and disease of human tissues is material accessibility. To overcome this obstacle, our group developed new technology by generating a 3D model system called brain organoids. This model system is derived from human stem cells and can recapitulate human-specific aspects of brain development. Using organoids permits us to model disorders which affect the nervous system and consequently offers the potential to fundamentally change disease research. In this project, we aim to bring brain organoid technology to the next level by instating neurological diseases in the lab, to understand them with the ultimate purpose to drive the generation of novel therapies. We hypothesize that the cross talk between cells of different brain regions can be studied in our model system making it a valuable tool to investigate the initial stages of a specific brain disorder before this becomes a recognizable pathology. To achieve this, we will generate organoids fusing distinct brain regions that are associated with specific brain circuits in a developmentally representative way. This will allow us to study neurological interactions between these regions in a petridish, for the first time. The new organoid model enables us to study disease related aspects of a neurological circuit, which is particularly targeted by addictive drugs and pharmaceutical compounds. The proposed project will recreate neurological disease pathology in the lab going far beyond existing models and establishing an innovative human disease model that can refine and complement existing research into these neurological disorders.