PhD Top-up Scholarships
08/03/2019 → 19/09/2021
University of Melbourne / Murdoch Children’s Research Institute
Dr Ann Frazier, Prof. David Thorburn, and Dr David Elliott
Differentiate human pluripotent stem cell (hPSC) models of mitochondrial disease to a cardiomyocyte cell fate in order to facilitate preclinical treatment studies and investigation of the underlying cellular mechanisms of disease in a clinically relevant cell type
Despite a number of treatments showing potential benefit, there are none currently certified for clinical use when it comes to mitochondrial disease (mito). With over 320 known genetic
causes, proving the therapeutic value of a treatment is difficult due to the heterogeneity of genetic diagnoses in patients, inadequate animal models, and the characteristic tissue specificity
of mito. Using a panel of human stem cell models we genetically engineered to mimic mutations known to cause mito, we can generate disease relevant human cell types in the lab allowing us to overcome the issues associated with animal models and tissue specificity. This project is turning our mito stem cell models into heart muscle cells to screen promising treatment options and study how each genetic mutation affects cell function in a disease relevant cell type.
This project has the potential to improve our understanding of the underlying cellular mechanisms behind mito, which may lead to an improved understanding of common symptoms. Additionally, this work could provide the preliminary evidence needed to support a personalised medicine approach to mito by linking targeted therapies to specific genetic causes. This would be the first step in identifying a clinically valid treatment option for these disorders that targets the underlying condition.