A Zebrafish Model Of Facioscapulohumeral Dystrophy For Therapy Development And Functional Studies
Funder
National Health and Medical Research Council
Funding Amount
$390,601.00
Summary
This project seeks to develop a zebrafish model for a genetic muscle-wasting disease called facioscapulohumeral dystrophy (FSHD). Our zebrafish model will enable us to better understand the biological mechanisms underlying the disease, as well as provide a platform for therapeutic testing and discovery.
Mechanosensitive properties and modulation of N-methyl-D-aspartate (NMDA) receptors by lipid environment. This project will provide new information about the molecular determinants which influence NMDA receptor channel gating that will significantly advance our understanding of a link between NMDA receptor function and many neurodegenerative diseases as well as pain and learning and memory. The outcomes of this project may lead to the discovery of novel lipid-based biomaterials for application i ....Mechanosensitive properties and modulation of N-methyl-D-aspartate (NMDA) receptors by lipid environment. This project will provide new information about the molecular determinants which influence NMDA receptor channel gating that will significantly advance our understanding of a link between NMDA receptor function and many neurodegenerative diseases as well as pain and learning and memory. The outcomes of this project may lead to the discovery of novel lipid-based biomaterials for application in medicine and the drug industry. This research is highly significant in relation to human health. The biological and nutritional aspects of polyunsaturated lipids and dietary fish oils have long been recognized. Thus this project will provide further knowledge that could benefit the health of the nation with consequent reduced health care costs.Read moreRead less
Nigel G Laing, NH&MRC Principal Research Fellowship: Neurogenetics – Gene Discovery, Pathobiology, Novel Therapeutics, Novel Diagnostics And Translation.
Funder
National Health and Medical Research Council
Funding Amount
$880,454.00
Summary
My Fellowship will expand my work identifying diseases genes for genetic muscle and nerve diseases by using new technologies that allow discovery of human disease genes which could not be found before. In addition, since we now have proof from mouse studies that heart actin is a target for therapy for the group of diseases that we discovered caused by mutations in the muscle actin protein, we shall take further steps towards making this therapy a reality for patients.
Discovery Indigenous Researchers Development - Grant ID: DI0560757
Funder
Australian Research Council
Funding Amount
$160,896.00
Summary
Identification and Characterisation of Genes involved in the Copper Regulation of the Human Alzheimer's Disease Amyloid-Beta Precursor Protein (APP) Gene. Alzheimer's disease (AD) is the most common form of dementia in the ageing population. This research project aims to identify and characterise new genes involved in the copper regulation of the Alzheimer's disease gene. This may lead to the development of novel therapeutic targets and clinical intervention strategies as well as early diagnost ....Identification and Characterisation of Genes involved in the Copper Regulation of the Human Alzheimer's Disease Amyloid-Beta Precursor Protein (APP) Gene. Alzheimer's disease (AD) is the most common form of dementia in the ageing population. This research project aims to identify and characterise new genes involved in the copper regulation of the Alzheimer's disease gene. This may lead to the development of novel therapeutic targets and clinical intervention strategies as well as early diagnostic procedures in preventative healthcare for the treatment of AD. The benefits would affect the international community as a whole, potentially minimising the socio-economic costs arising from the predicted world-wide increase in AD in the ageing population.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
Investigating The Pathogenic Mechanism Of Mutations In IQSEC2 Causing Non-syndromic Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$449,016.00
Summary
Intellectual disability is frequent in the population, as many as 1 in every 50 people in the world affected. Mutations in IQSEC2, an X-chromosome gene, cause intellectual disability. We will screen 1000 families with this disability for mutations in IQSEC2, building the picture of disease symptoms, contributing to informed genetic counselling. We will investigate functional impacts of these mutations in neuronal cultures, increasing our understanding of the causes of intellectual disability.
Molecular Genetics Of Hereditary Motor And Sensory Neuropathy With Pyramidal Signs
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
This project aims to determine the molecular cause of hereditary motor neuropathies with pyramidal signs by chromosomal linkage studies and to screen suitable families to locate genes with disease causing mutations. We propose to use the resources of the human genome project to locate the defective gene. In previous studies we have used these methods to identify genes of two other hereditary diseases of nerve. Our data suggests that this disorder forms part of the largest group of hereditary neu ....This project aims to determine the molecular cause of hereditary motor neuropathies with pyramidal signs by chromosomal linkage studies and to screen suitable families to locate genes with disease causing mutations. We propose to use the resources of the human genome project to locate the defective gene. In previous studies we have used these methods to identify genes of two other hereditary diseases of nerve. Our data suggests that this disorder forms part of the largest group of hereditary neuropathies yet to be defined. Because this disorder affects long spinal cord neurones, identifying the mutated gene and studying its function may shed light on possible mechanisms involved in other spinal cord diseases. This research is a systematic search and should lead to identifying the abnormal gene causing disease. Once the gene involved is known then an effective diagnostic test will be developed. When a test for the disease is available, it is likely that we will find that the disorder is more common than previously recognised. Knowledge of the function of the gene will lead to an understanding of how the disease develops and will eventually enable development of effective treatments.Read moreRead less
Genetic Bases For Charcot-Marie-Tooth And Hereditary Sensory Type 1 Neuropathies
Funder
National Health and Medical Research Council
Funding Amount
$618,055.00
Summary
This project aims to identify the defective gene in a hereditary disease of peripheral nerve. The hereditary disorders of peripheral nerve form the commonest group of human genetic diseases, collectively called Charcot-Marie-Tooth neuropathy. Although few hereditary nerve diseases are fatal most cause lifelong disability. All cause weakness of the lower legs and later weakness and wasting of the muscles of the arm and hand. Affected individuals have difficulty running, frequent falls with gradua ....This project aims to identify the defective gene in a hereditary disease of peripheral nerve. The hereditary disorders of peripheral nerve form the commonest group of human genetic diseases, collectively called Charcot-Marie-Tooth neuropathy. Although few hereditary nerve diseases are fatal most cause lifelong disability. All cause weakness of the lower legs and later weakness and wasting of the muscles of the arm and hand. Affected individuals have difficulty running, frequent falls with gradually increasing disability eventually requiring splints and other walking aids. We propose to use the newly developed resources of the human genome project to locate the defective gene. In previous studies we have used these methods to locate the defective genes of 2 other hereditary diseases of nerve. In this study we propose to investigate a newly recognised form of CMT called intermediate CMT. Intermediate CMT has characteristics intermediate between the better known forms of CMT affecting the nerve itself (the axon) or the nerve insulation (the surrounding myelin sheath). The disorder may therefore affect both components of nerve. The affected gene may mediate communication between the nerve and its sheath. This research should give valuable insight into the mechanisms responsible for the maintenance of normal nerve. Finding the gene may therefore have relevance to many other diseases of nerve. This research is a systematic search and should lead to the abnormal gene causing the disease. Once the gene involved is known then an effective test will be developed. When we can test for the disease, we probably will find that the disorder is much more common than previously recognised. Knowledge of the function of this gene will lead to an understanding of how the disease develops and will eventually lead to effective treatments.Read moreRead less
Molecular dissection of the functional regions of genes that encode actinins (ACTN2 and ACTN3) and their contribution to normal variation in skeletal muscle function. The project has discovered a common genetic variant that affects skeletal muscle structure, function and metabolism and influences athletic ability, and response to diet and exercise. The project will study how this gene influences muscle bulk and strength, the metabolic efficiency of muscle and the risk of obesity in the general ....Molecular dissection of the functional regions of genes that encode actinins (ACTN2 and ACTN3) and their contribution to normal variation in skeletal muscle function. The project has discovered a common genetic variant that affects skeletal muscle structure, function and metabolism and influences athletic ability, and response to diet and exercise. The project will study how this gene influences muscle bulk and strength, the metabolic efficiency of muscle and the risk of obesity in the general population.Read moreRead less