Using novel animal and stem cell models to investigate the role of genetic cardiac arrhythmia in sudden unexpected death in epilepsy (SUDEP).

Research Opportunity
PhD students, Masters by Research, Honours students
Number of Honour Places Available
2
Number of Master Places Available
1
Department / Centre
Medicine
Location
Florey Institute of Neuroscience & Mental Health
Primary Supervisor Email Number Webpage
Professor Christopher Reid christopher.reid@unimelb.edu.au +61390356372 Personal web page
Co-supervisor Email Number Webpage
Dr Ming Soh mingshiuan.soh@florey.edu.au +61383446875

Summary 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 contribute 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. Furthermore, the project aims to develop and measure 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.

Project Details

Epilepsy patients have increased risk of sudden unexpected death (SUDEP). It is difficult to do clinical studies over long timeframes due to the unexpected nature of SUDEP, thus highlighting the need for new preclinical models. Our recent publication showed that genetic dysfunction in a cardiac ion channel, which leads to cardiac arrhythmia and increased risk of sudden cardiac death, occurs in 10% of SUDEP cases. This gives us a unique opportunity to develop novel preclinical models based on the human genetic biomarker. There are two aspects to this project: mouse and stem cell models.

Using our recently engineered SUDEP mouse models that have the human-equivalent genetic heart dysfunction, we will perform EEG-ECG 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. Furthermore, we will also generate human iPSC-derived cardiomyocytes in 2D and 3D (mini heart organ) models carrying the genetic changes. These models will be used to probe heart function under the combined stress of genetically-caused cardiac dysfunction and simulated seizure.

The mouse and stem cell models will allow us to (1) understand cardiac role in SUDEP pathomechanisms, (2) test and repurpose therapies for cardiac arrhythmia to reduce SUDEP risk, and, (3) 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. Successful applicants will be able to learn a range of lab techniques from operating multi-electrode array system, optogenetics, to patch-clamp electrophysiology, perform EEG-ECG surgery/monitoring/analysis, mouse handling/injections, stem cell culture, molecular biology, and be involved in manuscript preparation. Please feel free to contact us (Professor Chris Reid christopher.reid@unimelb.edu.au or Dr Ming Soh mingshiuan.soh@florey.edu.au) if you are interested or would like to discuss the project further.



Faculty Research Themes

Neuroscience

School Research Themes

Neuroscience & Psychiatry



Research Opportunities

PhD students, Masters by Research, Honours students
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department / Centre

Medicine

Research Node

Florey Institute of Neuroscience & Mental Health

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