Investigation Of Cardiac Stem Cell Regenerative Capabilities And Their Enhancement By Manipulation Of Telomerase Reverse Transcriptase
Funder
National Health and Medical Research Council
Funding Amount
$491,462.00
Summary
Heart failure rates are increasing exponentially in Australia and worldwide. One in two people diagnosed with severe heart failure will die within one year of diagnosis. This burden of heart failure is underpinned by the heart’s limited capacity for self-repair after injury. This limitation could be overcome by stimulating newly discovered stem cell populations residing within the adult heart itself. This project investigates ways to harness and enhance the power of these stem cells.
Regulation Of Heart Development And Regeneration By DNA Methylation.
Funder
National Health and Medical Research Council
Funding Amount
$552,709.00
Summary
The adult mammalian heart has an extremely limited capacity for regeneration following a heart attack, which is in stark contrast to the robust regenerative capacity of the newborn heart. How and why mammals lose their ability to regenerate heart tissue after birth is not well understood. We propose a new approach to unravel the complex mechanisms that control gene expression during heart development in rodents and humans, which could provide new therapeutic avenues for heart regeneration.
Cardiovascular diseases and heart failure rates are increasing worldwide. This is largely a result of the heart’s limited capacity for self-repair. Stem cells now provide an exciting potential novel therapy. We have recently demonstrated the feasibility of this therapy in a preclinical model of heart attack. Nevertheless, further work is required before human clinical trials can take place. This project will dismantle barriers preventing progression to these clinical trials.
Cytoprotective And Metabolic Responses To Biased Agonists Acting At Cardiomyocyte Gq-coupled Receptors
Funder
National Health and Medical Research Council
Funding Amount
$723,742.00
Summary
Cell surface receptors mediate the response of cardiac muscle cells to hormones and transmitters by interacting with a repertoire of intracellular signalling proteins. Despite primary coupling to Gq proteins that activate shared pathways, four such receptors promote differing responses in cardiac cells. We will investigate signalling pathways differentially activated by the ?1A-adrenergic receptor that promote survival of cardiac muscle under conditions of cell damage or nutrient insufficiency.
The Role Of Micro-RNAs In Human Cardiomyocyte Specification
Funder
National Health and Medical Research Council
Funding Amount
$345,534.00
Summary
The heart is the first organ to form and is vital for the survival of the developing embryo. We are seeking to improve our knowledge of the process of heart formation. Understanding how primitive cells become cardiac cells may pave the way for production of “tailor made” cardiac cells for treatment of a weakened heart. It may also give insights to the causes of congenital heart defects (such as “hole in the heart” babies), which are the most common type of birth defects.
Identification And Characterisation Of Novel RNAs Involved In Cardiovascular Cell (de)differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$632,701.00
Summary
Several recent breakthroughs have made us realise that there is a lot of plasticity in cellular development, and we can now harness this plasticity to create stem cells that may eventually be used to repair the damaged heart and blood vessels after heart attacks and stroke. Here we will use mouse stem cells to discover the genetic factors responsible for a cell’s plasticity and memory in order to create pure populations of heart and blood vessel cells that can be used in repair settings.
Exploring The Role Of MicroRNA And Target Processing Variability In Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$605,190.00
Summary
microRNAs are gene regulators with critical roles in heart disease. How interactions between microRNAs and their messenger RNA targets change during disease is poorly understood. We hypothesise that these interactions are critically affected by altered processing of microRNAs and targets. We will thus characterise and validate such differences in healthy and diseased hearts. This will define gene regulatory changes underpinning heart disease and contribute to the search for better treatment.