Metabolic reprogramming of the failing heart

Research Opportunity
PhD students
Department / Centre
Paediatrics
Location
Royal Children’s Hospital/Murdoch Childrens Research Institute
Primary Supervisor Email Number Webpage
Dr Alejandro Hidalgo-Gonzalez alejandro.hidalgogon@mcri.edu.au 8341 6484
Co-supervisor Email Number Webpage
Dr Holly Voges holly.vogues@mcri.edu.au
A/Prof Enzo Porello enzo.porello@mcri.edu.au

Summary Metabolic reprogramming of the failing heart

Project Details

After a heart attack the heart muscle undergoes major cellular changes in order to preserve function and remain viable. These changes are believed to be an 'adaptive' mechanism to allow the heart muscle to continue to pump enough blood to the rest of the body. In the short term, these cellular changes successfully maintain function but failure to return to normal physiology leads to cellular dysfunction. Most of these physiological changes affect the mitochondria's capacity to produce energy and regenerate. Accumulation of dysfunctional mitochondria becomes a source of toxic subproducts that significantly contributes to cell death. The mitochondrion has been termed the powerhouse of the cell, considering it generates large quantities of energy. Due to its role, it is imperative that mitochondrial homeostasis is maintained to guarantee adequate energy generation for cardiac function and to reduce the production of toxic cellular subproducts. Mitochondrial quality control and recycling is orchestrated by a multiprotein complex that allows identification and degradation of damaged mitochondria. Modulation of one or multiple members of this complex could enhance mitochondrial regeneration and have potential for the treatment of diseased cardiomyocytes. To date, mitochondrial regeneration has not been explored as a therapy for heart failure. In this proposal, we will take advantage of our "heart attack" model from human pluripotent stem cells to validate factors for mitochondrial regeneration and improve cell survival, reduce cardiac muscle loss and increase contractility. This project will involve the generation of human heart cells from stem cells, cell culture, immunohistochemistry and confocal imaging.



Faculty Research Themes

Child Health

School Research Themes

Child Health in Medicine



Research Opportunities

PhD 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

Paediatrics

Research Node

Royal Children’s Hospital/Murdoch Childrens Research Institute

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