Using novel animal models to investigate the role of genetic cardiac arrhythmia in sudden unexpected death in epilepsy (SUDEP)
We recently provided evidence that epilepsy patients carrying loss-of-function variants in a cardiac arrhythmia gene are at greater risk of sudden death, known as SUDEP. This project aims to understand how genetic cardiac arrhythmia contributes to SUDEP risk by using EEG-ECG to monitor the changes in brain and heart function during seizures and sudden deaths in novel SUDEP mouse models. These models provide an opportunity to test cardio-protective strategies on SUDEP risk. Successful applicants will have the opportunity to learn to perform EEG-ECG surgery/monitoring/analysis, mouse handling/injections, molecular biology, and be involved in manuscript preparation.
Our research comprises two primary areas of focus:
1) Conduct EEG-ECG surgery and recording in mice to observe alterations in brain and heart functions.
2) Test established treatments for cardiac arrhythmia to minimize the risk of SUDEP.
We are aiming to develop and measure the electrophysiology of stem cell-derived cardiomyocytes, including 3D ‘mini heart’ cardiac organoids, that express the cardiac arrhythmia variant identified in SUDEP patients. These models provide an opportunity to test cardio-protective strategies on SUDEP risk. Successful applicants will have the opportunity to learn to operate multi-electrode array system, optogenetics, patch-clamp electrophysiology, perform EEG-ECG surgery/monitoring/analysis, mouse handling/injections, stem cell culture, molecular biology, and be involved in manuscript preparation.
Epilepsy patients have an increased risk of sudden unexpected death (SUDEP). Our recent publications showed that genetic dysfunction in cardiac ion channels, which leads to cardiac arrhythmia, can increase SUDEP risk, further highlighting the role of cardiac arrhythmia in SUDEP pathophysiology. This gives us a unique opportunity to develop novel preclinical models based on the human genetic biomarker.
Using our recently engineered SUDEP mouse models that have human-equivalent genetic heart dysfunction, we will perform EEG-ECG surgery and recording to monitor changes in brain and heart function during seizure and death events. We will also use this model to trial known treatments for cardiac arrhythmia to see if these reduce the risk of SUDEP.
The mouse models will allow us to:
- understand the cardiac role in SUDEP pathomechanisms
- test and repurpose therapies for cardiac arrhythmia to reduce SUDEP risk
- translate our findings to the clinic, where our biomarkers and treatment strategies can be used to identify epilepsy patients at risk and help determine the appropriate intervention.
Take part in this project
Students who are applying to study at The Florey can register their interest in this project. Refer to our step-by-step guide to help you with your application.
Successful applicants will join an experienced, friendly and supportive team, with the opportunity to learn a range of lab techniques from performing EEG-ECG surgery/monitoring/analysis, mouse handling/injections, animal behavioural experiments, molecular biology, and be involved in manuscript preparation.