Mitochondrial Ribosomal Pentatricopeptide Domain Proteins Regulate Protein Synthesis In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$444,108.00
Summary
Mitochondria in our cells regulate energy production from food and play an important role in health and disease. Defects in mitochondrial protein synthesis lead to severe neurodegenerative and sensory diseases and may contribute to cancer and ageing. This research aims to investigate the role of mitochondrial proteins that regulate translation in mitochondrial diseases. Characterisation of these proteins provides an unexplored resource of potential disease modulators and drug targets.
Regulation Of Gene Expression In Mitochondrial Disease
Funder
National Health and Medical Research Council
Funding Amount
$338,362.00
Summary
Mitochondrial diseases affect 4000 children every year and most of these children do not reach adulthood. These diseases result from defects in mitochondria, energy producing compartments within cells. We have discovered a protein that controls mitochondrial gene expression and used it to rescue dysfunction in cells from patients with mitochondrial disease. We will determine its function and role in cell health, allowing us to evaluate its importance in mitochondrial disease.
Xenobiotics - Oxidative Stress In The Mammalian Ovary
Funder
National Health and Medical Research Council
Funding Amount
$377,922.00
Summary
Synthetic chemicals called xenobiotics in the environment are capable of interfering with female fertility. Xenobiotics can trigger oocyte depletion of the ovary and infertility. Exhaustion of the oocyte population results in the menopause, loss of ovarian hormones and profoundly affects female health through increasing susceptibility to heart and bone disease. This research will characterise xenobiotic effects on the ovary and will lead to significant advances in reproductive healthcare.
Neurologic Effects Of Mutational Load In MELAS Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$505,786.00
Summary
This project will use a new stem cell model to discover what happens to brain cells in patients with the MELAS 3243A>G mutation, a common genetic mutation found in 1-500 Australians. Brain cells will be grown from our stem cell model and used to find out how this mutation causes problems in the affected brain cells. We will find out what happens to the brain when the amount of mutation is reduced in vitro. By understanding what happens, we will be able to design new treatments for this disord ....This project will use a new stem cell model to discover what happens to brain cells in patients with the MELAS 3243A>G mutation, a common genetic mutation found in 1-500 Australians. Brain cells will be grown from our stem cell model and used to find out how this mutation causes problems in the affected brain cells. We will find out what happens to the brain when the amount of mutation is reduced in vitro. By understanding what happens, we will be able to design new treatments for this disorder.Read moreRead less
Evaluation Of Pathogenic Mechanisms Involved In Nuclear And Mitochondrial DNA-encoded Mitochondrial Disorders
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Mitochondria produce energy for the cell. Disorders of mitochondrial function can cause human disease. These diseases are referred to as the mitochondrial disorders. Mitochondrial disorders usually involve multiple tissues, particularly the muscle and brain.These disorders are usually caused by mutations in two different types of DNA; nuclear and mitochondrial DNA. There are many forms of mitochondrial disorders; some affect young children or infants and others cause adult disease. In some cases ....Mitochondria produce energy for the cell. Disorders of mitochondrial function can cause human disease. These diseases are referred to as the mitochondrial disorders. Mitochondrial disorders usually involve multiple tissues, particularly the muscle and brain.These disorders are usually caused by mutations in two different types of DNA; nuclear and mitochondrial DNA. There are many forms of mitochondrial disorders; some affect young children or infants and others cause adult disease. In some cases, genetic defects may cause the same disease and other mutations may cause a wide range of symptoms. The reason why this occurs is unknown. This study investigates several factors that may determine why some mutations lead to a certain disease and why others may cause different diseases. These factors include the variation in energy levels that are produced by the mutant cells, and the different levels of vunerability that mutated cells may have to induced cell death. The goal of this proposal is to identify the factors that lead to mutations causing different clinical symptoms with the overall aim being to design treatment for these chronic diseases.Read moreRead less
Understanding The Metabolic Consequences Of Impaired AMPKa2 And NNOS� In Skeletal Muscle: Implications For The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$575,527.00
Summary
The inability of muscle to utilise sugar from the blood is a major problem that contributes to obesity and Type 2 diabetes. Since the number of people with these diseases will at least double by 2030, we need to find out what causes this problem. We will examine whether two muscle proteins that are impaired in obesity and Type 2 diabetes are also responsible for impaired sugar utilisation. We think that increasing these muscle proteins will fix the _sugar problem�, and remedy these diseases.
Short-term Effects Of Overfeeding On Metabolic Risk In Humans
Funder
National Health and Medical Research Council
Funding Amount
$417,196.00
Summary
The prevalence of obesity is rapidly increasing in Australia and other parts of the world. Obesity is closely associated with insulin resistance and plays a role in the development of type 2 diabetes. However, the effects of short-term periods of over nutrition in humans remain unclear. In the proposed study, we will investigate the effects of short-term weight gain by high fat feeding in lean subjects, in subjects who are overweight and in subjects who are genetically more likely to develop dia ....The prevalence of obesity is rapidly increasing in Australia and other parts of the world. Obesity is closely associated with insulin resistance and plays a role in the development of type 2 diabetes. However, the effects of short-term periods of over nutrition in humans remain unclear. In the proposed study, we will investigate the effects of short-term weight gain by high fat feeding in lean subjects, in subjects who are overweight and in subjects who are genetically more likely to develop diabetes (due to strong family history). The aims are to distinguish physiological and endocrine characteristics of individuals who store more fat in response to overfeeding. We will identify differences between these individuals and whether they have defects in upregulating machinery involved in fat oxidation and energy production in skeletal muscle that may help them adapt during to energy excess. We will look for changes in type 2 diabetes risk and we will have the potential to identify defects in factors that are involved in this response. We will also re-examine indivudals again after calorie restriction and weight loss. We also plan to confirm the role of the candidate genes involved in fat oxidation that have been identifieid in human studies by in vivo gene transfer technology in rodents. This study will determine whether overweight and lean subjects behave similarly when faced with an overfeeding challenge. We expect that individuals with a genetic predisposition for T2DM will become more IR, due to metabolic inflexibility and a decreased ability to upregulate machinery involved in fatty acid oxidation and mitochondrial function. By characterising the physiological and endocrine responses to overfeeding, we will establish quantifiable markers allowing us to distinguish those at risk and identify new targets for pharmacological or lifestyle intervention.Read moreRead less
Biology Of EGFR Mutations In Glioblastoma Multiforme
Funder
National Health and Medical Research Council
Funding Amount
$287,445.00
Summary
The epidermal growth factor receptor (EGFR) is a protein that has a critical role in the development of normal cells. In glioma, the most lethal of the brain cancers, the EGFR is altered. These alterations result in uncontrolled activation of the EGFR, causing signals that promote the growth and survival of brain cancer. This grant seeks to understand the nature of the signals mediated by the altered EGFR, in turn helping us develop better therapeutics for the treatment of this deadly cancer.
Defining The Genomic Basis Of Mitochondrial Complex I Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$639,682.00
Summary
The human genome project led to new technologies that will revolutionise genetic testing. Previously, we could only sequence genes one at a time. Next Generation sequencing allows analysis of hundreds or thousands of genes simultaneously. We will analyse 90 genes in 100 children with severe disorders of mitochondrial energy generation. This will provide proof of principle for the introduction of this technology into routine medical testing and identify new genes causing these diseases.