Using single-cell omics to determine disease mechanism and improve clinical management of children with epilepsy

Summary Using single-cell omics to determine disease mechanism and improve clinical management of children with epilepsy

Project Details

Epilepsy affects 1% of the world's population and is regarded by the World Health Organisation as the most serious brain disorder. Epilepsy typically presents in childhood, with over 50% of individuals having a focal seizure onset, and is associated with cognitive, intellectual, and behavioural disabilities and an increased risk of sudden death. In ~30% of children seizures cannot be fully controlled by medication. A major cause of drug-resistant focal epilepsy is a malformation of cortical development (MCD) which accounts for ~50% of childhood epilepsies that require surgery. The most common MCD causing epilepsy is focal cortical dysplasia (FCD), in which areas of the cerebral cortex show abnormal layering and dysmorphic neurons (DN) with or without balloon cells (BC). Surgery to remove the dysplastic tissue is often the only effective treatment to control seizures in these individuals, and our group is using this resected tissue to better understand the causes of FCD, with the aim of providing accurate diagnostic counselling and precision treatments.  Single-cell omics provides an unprecedented opportunity to explore and understand the molecular mechanisms that define individual cells in complex tissues, such as the brain.

This project will use the single-cell RNA-sequencing and single-cell chromatin accessibility profiling on brain tissue resected during epilepsy surgery to identify the most critical participants of epileptogenesis at both the cellular and molecular levels.