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.
This study is aimed at identifying genetic variants that influence susceptibility to migraine. We plan to use DNA samples already collected from families with multiple migraine affected individuals and sequence a region on the X chromosome that has previously been identified as harbouring a migraine susceptibility gene. This project will identify gene(s) that contain variants contributing to migraine.
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.
Transforming The Diagnosis Of Mitochondrial Disorders Using High-throughput Sequencing, Functional Prediction And Experimental Validation
Funder
National Health and Medical Research Council
Funding Amount
$670,794.00
Summary
The human genome project sparked enormous improvements in our ability to sequence DNA. “Next Generation” DNA sequencing can potentially sequence an individual’s entire genome in a week and has the ability to transform the diagnosis of inherited diseases but is as yet unproven in a medical genetics context. We will develop and validate the use of Next Generation sequencing to enable the rapid sequencing of over 1000 genes in which mutations cause inherited metabolic diseases.
P2X7 Mediated Phagocytosis Of Apoptotic Cells: A Common Mechanism Underlies Neurological And Eye Disorders
Funder
National Health and Medical Research Council
Funding Amount
$527,033.00
Summary
We have found a strong genetic linkage between a protein called P2X7 and a number of neurological disorders, in line with our recent discovery of a novel function of this protein in clearance of dying cells as removal of unhealthy neurons is essential to keep brain function promptly. Further study using genetic association, cell biology and animal models will lead to a conceptual advance on how neurological diseases are occurred and developed.
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.
Haplotype Variation At The Dopamine Transporter Gene (SLC6A3): Effects On Function, Endo-phenotypes, Cognition And ADHD
Funder
National Health and Medical Research Council
Funding Amount
$585,894.00
Summary
We will investigate variation in the dopamine transporter gene. Variation in this gene will be characterised to a deeper level than has been previously possible using the latest sequencing technology, its biological function will be investigated using biochemical and neuroimaging methods directly in human subjects, and its effects on a clinically important cognitive measure and a common psychiatric condition (attention deficit/hyperactive disorder) will we determined.
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.