Molecular and Cellular characterization of developing Fragile X Synapses in human assembloids

Fragile X syndrome is a condition that affects the development of the nervous system. It is a leading cause of autism, a prevalent neurodevelopmental condition that is currently untreatable. Fragile X animal models display deficits at the level of neuronal connections called synapses. In addition, other cell types are affected including astrocytes. Astrocytes are glial cells important for proper neuronal connectivity and function. Nevertheless, the structure of the astrocyte-synapse interactome, known as a tripartite synapse, remains largely unexplored in the developing human brain and disease. Researching these concepts has recently become possible thanks to organoid technology, one of the recent most important scientific advances. Organoids are 3D tissue structures derived from unspecialized cells, called stem cells.  Importantly, they can be grown to reliably mimic different parts of the human brain and assembled to study connectivity between brain areas. I plan to use fused cortical and striatal organoids to study striatal development in the context of cortico-striatal projections which are the central brain hub affected in autism. I will first look at the disease-induced molecular deficits in different cell types. Then, I will use state-of-art microscopes and develop computational approaches to conduct a longitudinal assessment of the morphological changes in synapses. Using brain organoids to characterize the tripartite synapse in Fragile X from different angles will give a more complete understanding of the disease onset which will be useful for the development of treatment for corticostriatal symptomatology.