Viral Therapy For Skeletal Muscle Alpha-actin Disease And Discovery Of Novel Neuromuscular Disease Genes And Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$324,028.00
Summary
This research project is the next logical step towards treating patients with skeletal muscle actin disease - using viral delivery of normal actin genes in animal models of actin disease. Another arm of this project is to investigate the genetics and mechanisms causing two very different groups of muscle disorders in the Australian population: devastating muscle weakness in the foetal akinesias and enhanced muscle strength and bulk in individuals with strongman syndromes.
The Effects Of ACTN3 R577X On Muscle Wasting And Repair, And Response To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$1,066,054.00
Summary
Complete loss of ACTN3 is normal and occurs in 1 in 5 people world-wide. While it does not cause disease, loss of ACTN3 results in ~10% reduction in muscle mass and strength. This has tremendous impact not only on the success of elite athletes but also the quality of life in people who are already frail. Precisely how ACTN3 affects muscle mass is unclear. Understanding this will help identify the patients who are at greater risk of muscle wasting and also the therapies that will best treat them.
Defining A Role For The STONED Proteins In The Synaptic Vesicle Cycle
Funder
National Health and Medical Research Council
Funding Amount
$301,527.00
Summary
Nerve cells communicate with each other by means of chemical neurotransmitters. The level of communication is strictly controlled, and changes in the level, either up or down, is known as synaptic plasticity. This plasticity is thought to underly changes in the brain that account for both long and short term memory. Uncontrolled alterations in plasticity can also induce abnormal brain function, resulting in neurological disorders. Changes in the release of neurotransmitter are regulated at the m ....Nerve cells communicate with each other by means of chemical neurotransmitters. The level of communication is strictly controlled, and changes in the level, either up or down, is known as synaptic plasticity. This plasticity is thought to underly changes in the brain that account for both long and short term memory. Uncontrolled alterations in plasticity can also induce abnormal brain function, resulting in neurological disorders. Changes in the release of neurotransmitter are regulated at the molecular level by unknown mechanisms, however the chemical neurotransmitters are enclosed in small vesicles and it is believed that the control of the release of these vesicles, and their recycling, are important components of this mechanism. We have identified a gene that encodes two novel proteins of neurotransmission. Mutations that alter these genes can result in either increased or decreased synaptic activity. By using a combination of genetic and molecular techniques we propose to investigate how one of these two proteins operate to alter synaptic activity, as well as attempting to show how it interacts with other components of the synaptic machinery.Read moreRead less
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.
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.
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.
Disease Gene Discovery And Improved Genetic Diagnosis In Neuromuscular Disorders
Funder
National Health and Medical Research Council
Funding Amount
$473,321.00
Summary
Paediatric nerve and muscle disorders result in weakness, chronic disability and often early death. Over half of all affected children do not yet have a genetic diagnosis. This project will use advanced sequencing technology to increase genetic diagnosis rates and identify new disease-causing genes. This will result in improved patient care and a better understanding of the biological pathways altered by these disorders. It will also facilitate the identification of targets for future therapies.
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.
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.