Approaches To Therapy For The Skeletal Muscle Actin Diseases
Funder
National Health and Medical Research Council
Funding Amount
$912,078.00
Summary
We have shown that errors in a crucial muscle protein called actin cause muscle diseases that affect newborn children. These diseases are mainly very severe, causing death within the first year of life. Currently there is no cure. This project will investigate possible therapies for these diseases, such as viral delivery of a normal version of actin and finding a drug to overcome the weakness. Successful outcomes will crucially bring treatment closer for the patients.
The Effects Of ?-actinin-3 On Muscle Metabolism, Human Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$643,060.00
Summary
We have identified a common genetic variant that results in absence of the fast muscle fibre protein ?-actinin-3 in more than one billion humans worldwide. Loss of ?-actinin-3 influences elite athletic performance, muscle bulk and strength in the general population, response to diet and exercise, and susceptibility to obesity and developing type 2 diabetes. We have also demonstrated that ?-actinin-3 influence disease severity in a variety of inherited and acquired muscle disorders.
Neuromuscular Disorders: Gene Discovery And Disease Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$880,569.00
Summary
Inherited muscle disorders lead to lifelong disability and early death. Less that 50% of patients get an accurate diagnosis and there are currently no effective therapies. In this project, two leading Australian laboratories will use state-of-the-art methods to identify novel disease genes and how they cause muscle weakness. This research will have immediate outcomes to diagnosis, management and prevention and for the development of new therapeutic agents.
Investigation Into The Roles Of A Novel Vertebrate Gene, S52, In CNS Development And Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$272,389.00
Summary
Developmentally regulated genes when mutated or deleted can cause a variety of diseases including neurological diseases in humans. It is therefore important to understand the fundamental molecular genetics of development. We have discovered a novel human gene, termed S52, and its equivalent gene in the mouse. The predicted protein derived from these genes would indicate that S52 protein may interact with other proteins, possibly nerve growth factors, in the body to regulate normal development an ....Developmentally regulated genes when mutated or deleted can cause a variety of diseases including neurological diseases in humans. It is therefore important to understand the fundamental molecular genetics of development. We have discovered a novel human gene, termed S52, and its equivalent gene in the mouse. The predicted protein derived from these genes would indicate that S52 protein may interact with other proteins, possibly nerve growth factors, in the body to regulate normal development and possibly facilitate the survival of nerve cells in embryos. Strikingly, the worm C. elegans, an evoluationary very distant animal, also has a very similar gene to human. The fact that the protein has been so conserved throughout evolution supports the idea that S52 function is important in development. S52 mRNA is expressed in the developing brain, particularly in a special group of cells called the floor plate. Floor plate is a tissue that has ability to organize the patterning and differentiation of cells within the developing brain. S52 is also expressed in motor neurons in early stages of development and later in a subset of dorsal spinal cord neurons. We have mapped S52 to the short arm of human chromosome 2 (2p15-22). This region of chromosome 2 is linked to several human genetic diseases with neurological defects. Based on our preliminary data, we think S52 is not only important for normal brain development but may be mutated in a human neurological disease called Spastic Paraplegia Type 4 (SPG4) which is characterized by a degeneration of nerve cells in the spinal cord. The aim of this project is to further our understanding of the function of this gene and investigate its role in disease. This knowledge will contribute to an overall increase in our understanding of the molecular basis of brain development and neurological disease in humans.Read moreRead less
Role Of Chromatin Structure In The Regulation Of Stem Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$272,036.00
Summary
The aim of this project is to understand more about the nature of stem cells. Stem cells are cells which have the capacity to proliferate indefinitely but, at the same time, retain the capacity to differentiate into one or more cell types. Lower animals, such as amphibians, have a much greater capacity than humans to regenerate body parts. For example, axolotls can regenerate an entire limb if one limb is injured. This is because they retain undifferentiated stem cells in their limbs which can b ....The aim of this project is to understand more about the nature of stem cells. Stem cells are cells which have the capacity to proliferate indefinitely but, at the same time, retain the capacity to differentiate into one or more cell types. Lower animals, such as amphibians, have a much greater capacity than humans to regenerate body parts. For example, axolotls can regenerate an entire limb if one limb is injured. This is because they retain undifferentiated stem cells in their limbs which can be reactivated in the event of injury. Interestingly the adult human brain contains a small population of stem cells. The aim of this project is to find out more about how these cells remain undifferentiated and what is it about them which allows them to form different cell types. If more is known about these cells maybe in the future it will be possible to stimulate them to repair damaged parts of the nervous system. It may also be possible to treat people suffering from diseases like Alzheimer's disease, Parkinson's disease or spinal injuries.Read moreRead less
Gene Discovery And Pathobiology In Muscle Diseases
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
I aim to find the genetic causes of muscle diseases that are lethal or severely debilitating. These diseases result in a significant burden to the affected individuals and their families and also on Australia’s Health care system. A genetic diagnosis provides families with answers, allows family planning, such that couples do not have another affected child, enables appropriate clinical management and gives researchers evidence as to how to develop treatments.
Copper Homeostasis And APP-induced Neurodegeneration In Drosophila
Funder
National Health and Medical Research Council
Funding Amount
$381,223.00
Summary
Alzheimer s disease, a debilitating neurodegenerative disorder suffered by many of our elderly, is characterised by the presence of abnormal protein accumulations called plaques in the brains of affected patients. Plaques contain amyloid protein and also have high levels of the essential metals copper and zinc. Copper is needed for the formation of these protein aggregations and increases the toxic effects of amyloid, leading to the idea that copper-binding chemicals could be used to treat Alzhe ....Alzheimer s disease, a debilitating neurodegenerative disorder suffered by many of our elderly, is characterised by the presence of abnormal protein accumulations called plaques in the brains of affected patients. Plaques contain amyloid protein and also have high levels of the essential metals copper and zinc. Copper is needed for the formation of these protein aggregations and increases the toxic effects of amyloid, leading to the idea that copper-binding chemicals could be used to treat Alzheimer s disease. However experiments in animal models have produced conflicting results, some suggesting that increased copper levels protect against neuronal damage while others claim the opposite effect. Comparison of these studies is hampered by the different experimental systems used. We will clarify the role of copper in the progression of Alzheimer s disease using a simple insect model, the fly Drosophila melanogaster. Production of amyloid in Drosophila neuronal tissues produces a neurodegenerative effect similar to that seen in human brains, but in a matter of weeks rather than the years required in humans. We will combine production of amyloid with production of copper uptake and export proteins to investigate the effect of changing copper levels. We will also test the effect of increasing copper and other metals in the diet to see whether dietary levels are an important factor in disease progression. Finally, we will use the Drosophila model to test large numbers of metal binding compounds and drugs for ones that slow or halt the neuronal damage caused by amyloid production, identifying potential therapeutics for the treatment of Alzheimer s disease. This work will provide a vital and definitive clarification of the role of copper in the progression of Alzheimer s disease and potentially lead to the development of novel treatments for this disease that is rapidly becoming a major social and economic problem in the developed world.Read moreRead less
PArkin Co-Regulated Gene (PACRG), Parkin And Parkinsonism.
Funder
National Health and Medical Research Council
Funding Amount
$397,740.00
Summary
Parkinson's disease (PD) is a common neurodegenerative disorder affecting greater than two percent of individuals over the age of 65. The disease is characterised by tremor, slowness of movement, rigidity and postural instability. Current treatment regimes may provide some measure of symptomatic relief, but currently there is no treatment to halt or slow the progression of this debilitating disease. PD currently affects an estimated 35,000 people in Australia and this figure is predicted to incr ....Parkinson's disease (PD) is a common neurodegenerative disorder affecting greater than two percent of individuals over the age of 65. The disease is characterised by tremor, slowness of movement, rigidity and postural instability. Current treatment regimes may provide some measure of symptomatic relief, but currently there is no treatment to halt or slow the progression of this debilitating disease. PD currently affects an estimated 35,000 people in Australia and this figure is predicted to increase significantly as the population ages. PD is a complex disorder, the causes and disease mechanisms are not well understood. However, in the past 10 years several genes have been identified that can cause PD when disrupted. We have identified a new gene that we believe may be involved in PD. The overall aim of this proposal is to characterise this gene and what role it plays in the development of PD. Understanding the expression and function of this gene may significantly advance our understanding of this disorder. Using these results, we aim to model Parkinson's disease in cellular and animal systems; these may provide powerful insight into the molecular pathway(s) perturbed in PD and a means to develop novel therapeutic approaches to alleviate or prevent the disorder.Read moreRead less