Therapeutically Targeting The Major Genetic Risk Factor Of Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$530,069.00
Summary
The second greatest risk factor for Alzheimer’s disease (after age) is genetic variation in a protein called APOE, however it is unknown why APOE increases the risk of disease. We have new clinical and laboratory evidence that APOE incresase risk of Alzheimer’s disease by manipulating iron pathways in the brain. We plan to examine these pathways and apply a new theraputic we have developed that targets these pathways in animal models of Alzheimer’s disease.
Novel Interplay Of Oestrogen And Growth Hormone In Regulating Lipid Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$673,045.00
Summary
These studies provide insights into the mechanisms and role of oestrogen in regulating whole body and liver fat metabolism. Oestrogen-related medications that modify the action or tissue availability of oestrogen are widely used therapeutics and can predispose to obesity and fat accumulation in the liver. Whether the effect is direct or through interplay with other metabolic hormones is unknown. This proposal examines their metabolic consequences and impact on obesity and liver health.
Antiphospholipid Syndrome Related Thrombosis: Understanding The Disease Pathogenic Mechanisms Is The Key To Better Diagnosis And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$607,497.00
Summary
Patients with the Antiphospholipid Syndrome develop thrombosis at a young age. It requires long-term treatment with blood thinning medications, which have risks of severe bleeding. Methods are needed to decide which patients require long term treatment, avoiding unnecessary treatment in low risk patients. Such methods do not currently exist. In this study we explore how useful two novel assays developed by us are in identifying which of these patients are at high risk of thrombosis.
The Role Of Redox-related Post-translational Changes Of Complement Factor H (CFH) In Age-related Macular Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$652,019.00
Summary
Patients with AMD experience loss of central vision and this disorder is the leading cause of blindness in those aged over 50 years in Australia. There are currently no effective treatments for dry AMD. We have identified a protein that undergoes a modification in the blood and the eyes of humans with AMD that has given us new insights into how AMD develops. Specific therapies targeting this modified protein may offer a new treatment for this important cause of blindness.
ABCA1 _ An Intersection Between Infection, Atherosclerosis And Metabolic Disorders
Funder
National Health and Medical Research Council
Funding Amount
$653,827.00
Summary
Pathogens interfere with cellular cholesterol metabolism in order to support their lifecycle. Such interference may cause diseases not usually associated with infection, like cardiovascular disease. Restoring normal cholesterol metabolism may help treating infection and its metabolic consequences. We will investigate molecular, cellular and physiological mechanisms of interaction of pathogens with cholesterol metabolism to find a key point that can be targeted for therapeutic intervention.
Many drugs modulate the function of proteins imbedded in cell membranes. Extensive research has been undertaken to better understand drug interactions with these proteins to improve drug therapies, but there has been relatively little progress in understanding the role of the cell membrane. This project will investigate how the cell membrane influences protein function and then use this information to develop novel drugs for the treatment of neurological disorders.
S100 Proteins: Novel Oxidant Scavengers In Allergic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$505,814.00
Summary
Allergic inflammation includes conditions such as dermatitis and asthma. Asthma, affects one in 10 adults and one in 6 Australians, costing ~$720 million/annum. We will characterize new mediators of oxidant defence which have suppressive effects on key pathogenic processes. The novel oxidative changes in S100 proteins may lead to new diagnostic reagents and new strategies for therapy. Results will open new frontiers in asthma biology and will apply to other chronic inflammatory diseases.
How Does Disruption Of Serinc1 Expression Affect Lymphocyte Function And The Development Of Autoimmunity?
Funder
National Health and Medical Research Council
Funding Amount
$681,555.00
Summary
Autoimmune diseases affect up to 8% of the population. We have recently discovered a novel gene mutation in mice that results in increased levels of anti-nuclear antibodies, a hallmark of various autoimmune diseases in humans. The mutated gene, Serinc1, has not been previously implicated in autoimmune disease, but it is important for synthesis of key molecules in immune cells. This research proposal aims to determine how disruption of Serinc1 contributes to the development of autoimmune disease.
An Essential Role For Skeletal Muscle FoxO1 In Protecting Against Obesity-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
Skeletal muscle is the largest organ in the human body and accounts for approximately 80% of glucose disposal after a meal. We have identified a transcription factor, namely FoxO1, that appears protect against obesity-induced insulin resistance by promoting energy consumption. This project will examine whether skeletal muscle specific activation of FoxO1 is a possible therapeutic target for the treatment of obesity-induced insulin resistance.
Molecular Characterization Of SEIPIN Function: Implications For Lipogenesis And Adipogenesis
Funder
National Health and Medical Research Council
Funding Amount
$767,468.00
Summary
Obesity and type II diabetes have become a major health threat to Australians. This project aims to understand how fat is made and stored. Results from this research may lead to novel therapeutic strategies against obesity and diabetes.