Modelling heart disease in a dish using patient-derived stem cells and drug screening

Research Opportunity
PhD students, Master of Biomedical Science
Number of Master Places Available
2
Primary Supervisor Email Number Webpage
A/Prof Enzo Porrello enzo.porrello@unimelb.edu.au Personal web page
Co-supervisor Email Number Webpage
A/Prof David Elliott

Summary The Cardiac Regeneration Group is focused on the development of novel therapeutic approaches for congenital and acquired forms of heart disease based on a deep understanding of developmental and regenerative biology

Project Details

The Cardiac Regeneration Group is focused on the development of novel therapeutic approaches for congenital and acquired forms of heart disease based on a deep understanding of developmental and regenerative biology. Our laboratory uses a variety of approaches including molecular genetic studies in mice through to single cell transcriptomics, gene editing (CRISPR/Cas9) in human pluripotent stem cells, as well as disease modelling and drug screening in human cardiac organoids. We are working closely with clinicians and scientists both nationally and across the Melbourne Children’s precinct to foster knowledge transfer and translation of research discoveries from bench to bedside.

 One key area of our heart research focuses on creating stem cells from patients with congenital heart disease and recreating their heart tissue in our laboratories. This allows us to recreate and study their disease more closely – this method of research is called disease modelling. If we are able to determine a genetic cause for the disease through studying a patient’s tissue in the laboratory, we now have the gene editing capability and technology to correct mutations found in that patients’ genome. By comparing a patient’s genetically mutated and corrected cell lines, we are able to better understand a disease’s cause and progression, which informs our understanding of any potential preventative measures, tests for that disease, developing new treatments and hopefully cures. We are also investigating whether iPS-derived cardiac organoids can be used to screen for drugs that promote regeneration of cardiomyocytes in children with heart disease. 

This project will develop iPS disease models of congenital heart disease for high-content screening to discover novel disease mechanisms and potential drug targets. PhD students will develop skills in iPS cell culture and differentiation including 3D organoids, gene editing, microscopy, transcriptomics/proteomics and cardiomyocyte physiology. High-content screening will be facilitated by the development of genetically encoded reporters to assess calcium handling, electrophysioloigcal properties, cell cycle status and biomechanical forces in iPS-derived cardiomyocytes. Candidate genes/pathways identified in the screen will be further validated and characterised using sophisticated genetic, biochemical and physiological approaches including gain/loss of function, contractility assays in 3D organoids and transcriptomics approaches (including single cell profiling). 




Research Opportunities

PhD students, Master of Biomedical Science
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.


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