Functional Genomics of Human Brain Development Cluster

Neurodevelopmental conditions like autism, attention deficit hyperactivity disorder (ADHD), epilepsy, and intellectual disability affect millions of children worldwide. These conditions are highly complex, and their causes remain elusive. Recent technological advances have revealed that genetics play a crucial role in these disorders. However, we still need to understand how specific gene variations disrupt the development of the human brain and lead to alterations that disrupt the lives of affected individuals. Our goal is to unlock the secrets behind neurodevelopmental disorders and find ways to help affected children and their families lead better lives. Our team of scientists will be using brain organoids, three-dimensional "avatars" of the human brain grown in the lab from human stem cells, to study the developing brain in a more accurate and detailed way. These organoids mimic some of the cellular complexity of the human brain better than previous methods, allowing us to study how genes influence brain development and function. We will initially focus on the cerebral cortex, a critical brain region responsible for higher functions like planning and memory. By studying brain organoids containing different types of brain cells, we aim to discover the role of specific genes associated with neurodevelopmental disorders. This research will help us identify the causes of these conditions and pave the way for developing targeted treatments. One significant challenge is that brain organoids created in different labs can vary, affecting the reliability of the research. To overcome this, we will create a standardised platform for generating brain organoids, ensuring consistency and reproducibility across multiple research centres in the UK. We will also use cutting-edge technologies like single-cell genomics, imaging, and electrophysiology to analyse brain organoids and unravel the intricate pathways contributing to human brain development in health and disease. We will also investigate how different people's genetic backgrounds influence these disorders, ensuring our findings are representative and applicable to diverse populations. We will bring together scientists from eight institutions in the UK and worldwide. Team members from these institutions are already collaborating by sharing resources and data. By developing this platform, we can extend these interactions and combine their expertise to share our findings and resources nationally. This approach will multiply our collective capacity to investigate the molecular mechanisms regulating brain development and their dysregulation in disease. We will accelerate the ability of other researchers to carry out investigations using brain organoids through dedicated training, sharing of protocols, and outreach programs in which we will interact with researchers and the general community, facilitating effective knowledge-sharing across multiple groups of individuals. In summary, this collaboration will accelerate our understanding of the biology underlying human brain development and the role that specific gene changes play in acquiring a neurodevelopmental condition. We envision that this knowledge will ultimately help identify new ways to improve the lives of children and families affected by these conditions.