Ion channels are expressed in multiple tissues and ion channel mutations can lead to a broad range of diseases (channelopathies), including various forms of severe childhood epilepsy. As part of their diagnosis, children with severe epilepsy are often screened for mutations.
However, the functional consequence of an identified pathogenic mutation is in many cases unknown and selecting the appropriate treatment is difficult, often resulting in escalation to polytherapy (administration of multiple drugs simultaneously). For many children, the treatment causes severe side effects and for around 30% of the children the treatment is ineffective. Establishing an appropriate and personalized treatment strategy contributes to improved cognitive and social development and quality of life for children with epilepsy.
Method
Patch-clamp recordings are a powerful technology used to determine the functional consequence of an ion channel mutation. In this project, we will perform such patch-clamp recordings to characterize the interaction of epilepsy drugs with key epilepsy-related ion channels. We will generate a dataset of recordings from genetically manipulated human cells that each express one key ion channel and assess how epilepsy ion channel drugs interact with that channel. Using computational methods, we will establish the mathematical equations that capture the dynamics of these recordings. These equations will be integrated into a model that can simulate how genetically manipulated neuronal cells respond to drug treatments.
