Modellling severe childhood epilepsy

Summary Epilepsy is a common neurological disorder with a third of patients not responding to currently available treatments. To better understand the underlying mechanisms, our lab is developing and analysing disease models for genetic forms of epilepsy.

Project Details

An increasing number of genetic variants affecting ion channel genes and associated with severe forms of epilepsy has been identified in recent years. To understand how these variants contribute to the disease phenotype, we perform the functional characterization using different in vitro and in vivo approaches.

Initial screen of detected variants is performed in Xenopus laevis oocytes or HEK cells and involves site-directed mutagenesis, RNA production and injection, cell culture methods and two-microelectrode or patch-clamp technique. In addition, biochemical methods and immunocytochemistry are applied to examine the expression and localization of affected channels. For some of the disease variants, we have also generated genetic mouse models that can provide information about the seizure and behavioural phenotype. To analyse the impact of disease mutations in the human biology context, we use induced pluripotent stem cells derived from patients carrying the specific mutation. These patient-specific stem cell lines and corresponding controls are then used for neural differentiation into 2-D and 3-D cultures that are studied using different molecular, morphological and electrophysiological assays.

Positions are available for examining several mutations linked to severe forms of epilepsy, with the aim to assess the disease mechanisms using some of the mentioned disease models. The identified disease markers will be used to screen and develop novel therapies.