Functional Genomic Analyses Of Mitochondrial Disorders
Funder
National Health and Medical Research Council
Funding Amount
$577,001.00
Summary
Mitochondria produce most of the energy required by our bodies. Mutations in genes that make mitochondrial proteins cause mitochondrial dysfunction and lead to neurodegenerative and muscular diseases. We will identify mutations in mitochondrial genes in members of different Bulgarian and Gypsy families and discovery the mechanisms by which the mutations lead to disease.
Regulation Of RNA Processing In The Mitochondrial Disease MELAS
Funder
National Health and Medical Research Council
Funding Amount
$520,977.00
Summary
Mitochondria are microscopic, energy producing machines that are found in all human cells. Mitochondria contain a small set of genes that must work properly to make the energy our bodies require for health. Defects in the expression of mitochondrial genes cause debilitating diseases for which there are currently no cures. We have developed a new set of technologies that will be applied to understand how these mutations cause disease and provide insights into possible treatments.
Systems Approaches To Understanding The Assembly Of Mitochondrial Machines
Funder
National Health and Medical Research Council
Funding Amount
$600,005.00
Summary
Mitochondria produce the energy for our bodies. Defects in this process cause mitochondrial disease, which affects at least 1/5000 people. Diagnosis is often inconclusive as we do not understand the function of many proteins important in mitochondrial energy production. State of the art CRISPR gene-editing tools will be coupled with advanced proteomics techniques to model different types of mitochondrial disease and identify the functions of new candidate disease genes.
Assembly And Misassembly Of Mitochondrial Respiratory Chain Complex I
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Mitochondria are the powerhouses in our cells. They burn the carbon fuels we eat and store the energy by making ATP that is used for functions such as muscle contraction and triggering of nerves. Mitochondrial Complex I is a molecular motor that helps to make ATP. “Mitochondrial disease” is often seen when Complex I is not built properly and this results in early childhood death. In this project we will study how Complex I is built and how the mitochondria responds to assembly problems.
The Structure And Organization Of The Mitochondrial Genome In Health And Mitochondrial Disease
Funder
National Health and Medical Research Council
Funding Amount
$553,646.00
Summary
Mitochondrial DNA (mtDNA) mutations and mitochondrial dysfunction have been associated with a wide range of multi-system human diseases, although much remains to be learnt about molecular mechanisms in the pathogenesis of these diseases. Our goal is to understand how the expression of the mitochondrial DNA is regulated by mtDNA-binding proteins that will allow us to provide important insights into the molecular mechanisms of mitochondrial diseases.
Apoptosis Inducing Factor And The Progression Of Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$496,756.00
Summary
There has been a dramatic increase in the rates of diabetic kidney disease. It now affects more than 400,000 Australians and places these individuals at an extremely high risk of death from a heart attack or stroke. This research is focusing on the powerstations of the cell, the mitochondria, which are responsible for energy production from the food we eat. We aim to investigate new novel targets to prevent the dysfunction of these power stations, with a view to discovering a new therapy for dia ....There has been a dramatic increase in the rates of diabetic kidney disease. It now affects more than 400,000 Australians and places these individuals at an extremely high risk of death from a heart attack or stroke. This research is focusing on the powerstations of the cell, the mitochondria, which are responsible for energy production from the food we eat. We aim to investigate new novel targets to prevent the dysfunction of these power stations, with a view to discovering a new therapy for diabetic kidney disease.Read moreRead less
The Role Of Accessory Subunits And Assembly Factors In The Biogenesis Of Respiratory Chain Complex I
Funder
National Health and Medical Research Council
Funding Amount
$569,987.00
Summary
The mitochondrial respiratory chain produces most of the energy required for our cells to grow and function. Complex I is the first enzyme of this chain and its defects are the most prevalent cause of mitochondrial disease, which often results in infant fatality. Defects in complex I have also been associated with Parkinson's disease and oxidative stress. This study will provide important new information into how complex I is built and what goes wrong to cause disease.
Innovative Use Of Hydrogel Technology To Recapitulate And Investigate Cardiac Pathology.
Funder
National Health and Medical Research Council
Funding Amount
$716,162.00
Summary
Hypertrophic cardiomyopathy is the leading cause of sudden death in the young. No treatment exists that can reverse or prevent it, primarily because the underlying mechanisms of the disease have not been fully elucidated. I will use innovative hydrogel technology to simulate the disease state. I will use this as a tool to identify the mechanisms involved with development of the disease. This will enable identification of potential therapeutic targets for prevention of the disease.
The L-type Calcium Channel As A Reporter Of Successful Morpholino Oligomer Therapy In Treatment Of Duchenne Muscular Dystrophy Cardiomyopathy
Funder
National Health and Medical Research Council
Funding Amount
$595,062.00
Summary
Duchenne Muscular Dystrophy is a fatal muscle wasting disorder. We have previously characterised how the heart fails in a mouse model of muscular dystrophy. We now have preliminary data demonstrating that treatment of mice with morpholino oligomers can rescue cardiac function. This project will fully characterise the effect of the treatment on heart function and optimise therapy regimes with the view to utilising the optimised protocol as a guideline in treating cardiomyopathy in Duchenne Muscul ....Duchenne Muscular Dystrophy is a fatal muscle wasting disorder. We have previously characterised how the heart fails in a mouse model of muscular dystrophy. We now have preliminary data demonstrating that treatment of mice with morpholino oligomers can rescue cardiac function. This project will fully characterise the effect of the treatment on heart function and optimise therapy regimes with the view to utilising the optimised protocol as a guideline in treating cardiomyopathy in Duchenne Muscular Dystrophy boys.Read moreRead less
Role Of UBL-5 In Mitochondrial Function And Glucose Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$647,539.00
Summary
Type 2 diabetes is caused by insulin resistance, a condition that is characterised by the inability of insulin to elicit its normal function to lower blood sugar levels. The cause of insulin resistance is not known. In this study we will determine the role of a novel gene called UBL-5 to elicit insulin resistance in muscle and fat by generating genetically-induced models in which this gene has been deleted. By understanding the role of UBL-5 in insulin resistance, better therapeutic strategies c ....Type 2 diabetes is caused by insulin resistance, a condition that is characterised by the inability of insulin to elicit its normal function to lower blood sugar levels. The cause of insulin resistance is not known. In this study we will determine the role of a novel gene called UBL-5 to elicit insulin resistance in muscle and fat by generating genetically-induced models in which this gene has been deleted. By understanding the role of UBL-5 in insulin resistance, better therapeutic strategies can be developed to treat Type 2 diabetes.Read moreRead less