Understanding how genetic variants affect neurodevelopmental disorders

This research cluster’s work will help to accelerate our understanding of how gene variation may contribute to neurodevelopmental disorders, such as epilepsy, schizophrenia and intellectual disability as well as conditions such as autism and ADHD.

Understanding how genetic variants affect neurodevelopmental disorders

Recent technological advances have made it possible to explore the genetic roots of many brain disorders and conditions. But gene associations are often linked to multiple disorders, raising an important question: how do similar variants in specific genes increase the likelihood of these diverse conditions? While we have a better understanding of which genes increase the likelihood of certain conditions, understanding how genetic variation in these genes influences brain development and contributes to these conditions remains a key challenge.

To speed up our understanding we’ll establish a platform to grow advanced lab-grown brain models. These brain organoids, closely mimicking human brain development, form functional neural networks. We’ll start by focusing on the cerebral cortex, the brain region where genetic changes linked to these disorders are most concentrated in specific cell types. Using our knowledge of brain development, we’ll build cortical organoids with the necessary diversity of neural cell types. This will allow us to understand how genetic variants impact the brain development, and specifically the function of specific neural cell types.

Using genome editing we’ll investigate the role of disorder-associated genes in human cortical development. We’ll generate and analyse these organoids with various techniques, including single-cell genomics, imaging, electrophysiological, and computational tools to analyse their development. This will reveal changes in gene expression, regulatory networks, and neural activity linked to specific mutations, helping us to understand the pathways contributing to disease.