Lundbeckfonden - DEVELOPNOID - Characterizing early brain development in health and disease using brain organoids

When the brain does not develop correctly, diseases develop over time, from a few years to decades later. This can be studied in animals but not easily in humans. Using breakthrough technology, DEVELOPNOID will show how this can be done in a new model of human brain. The model produces induced pluripotent stem cells (iPSCs) from patients’ blood and differentiates them into brain organoids (BOs), the first exciting model for human brain 1/87R350-2020-1113 development. When appropriately cultured, BOs mimic early stages of development and reveal changes in brain diseases. Development is affected by signals which alter cell connections, pathways and contents over time, not detectable by genomics, but reflected in cell proteins and their chemical controls (post-translational modifications (PTMs)). Disrupting such mechanisms leads to later malfunctions, leading to progressive neurological diseases. We will develop the first platform to produce BOs from iPSCs at large scale. BOs will be derived from healthy individuals and Alzheimer’s or schizophrenia patients. We will map the cellular signaling processes in early brain development and the changes that occur. Our powerful technologies in proteomics, PTMomics, metabolomics, transcriptomics, imaging and bioinformatics will be deployed. We expect to reveal new molecular processes like how mature neurons communicate. This project will also show how BOs reveal disease causative mechanisms that might ultimately be targeted with disease-modifying drugs.