Genes to networks – insights into dynamic brain pathology from genetic epilepsies

Epilepsy is one of the most common primary neurological conditions of childhood. Many of the severe childhood epilepsies are caused by mutations in neuronal genes. Some of these mutations can also induce epileptic seizures in zebrafish larvae, making them a useful animal model of the disease. They are particularly interesting to study because light-sheet microscopy allows us to record their brain activity at single-cell resolution.

I will analyse EEG recordings from patients, and light-sheet microscopy from zebrafish larvae with mutations in two ‘epilepsy genes’ (SCN1A, and GRIN2A). I will combine these recordings with advanced computational analysis tools which will allow me to identify how molecular abnormality induced by a mutation causes abnormal neuronal function, ultimately resulting in whole-brain dynamics that underlie epileptic seizures.

This more detailed understanding of the genotype-phenotype relationship will help in developing novel, targeted therapies for epilepsy.