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The Role Of Reduced Phagocytosis In The Pathogenesis Of Age-related Macular Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$786,742.00
Summary
Understanding the underlying mechanisms which lead to age-related macular degeneration (AMD) is critical if we are to ultimately develop novel treatments. We hypothesise that there is a defective ability to remove debris that accumulates in the retina as we age and this is a crucial step in the development of AMD. We will investigate this hypothesis in an AMD cohort and in a pre-clinical model where we will test the efficacy of an intervention that improves the ability to clear debris.
The Role Of The Complement System In Neurodegeneration And The Therapeutic Potential Of Complement Inhibition
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
This project aims to identify the role of immune and inflammatory components in the pathology of neurodegenerative disease. Additionally, this research will determine whether a new class of novel anti-inflammatory drugs can alter the neurodegenerative process. This will allow for an increased understanding of the biology of neurodegenerative disease, and also may lead to the development of new treatments for conditions such as Parkinson’s disease, Huntington’s disease and motor neuron disease.
Age-related Macular Degeneration: A Cause And A Cure
Funder
National Health and Medical Research Council
Funding Amount
$828,300.00
Summary
Age-related macular degeneration (AMD) is a leading cause of vision loss and there is urgent need for an intervention to slow disease progression. AMD is characterised by debris accumulation in the retina and I will investigate if loss of function in cells that should clear this debris is a critical step in the development of AMD. I will trial a novel laser intervention to slow progression of disease and use basic science techniques to investigate the mechanisms of action of the laser.
The Nutritional Geometry Of Ageing In A Rodent Model
Funder
National Health and Medical Research Council
Funding Amount
$979,269.00
Summary
A central belief in ageing research is that eating fewer calories prolongs life, and that the source of calories (carbohydrate, fat or protein) is irrelevant. However, a critical assessment indicates that this conclusion is premature. We will use recent techniques in nutrition to define for the first time in mammals the relationship between diet and ageing in a normal and a prematurely ageing strain of mice. The project will provide a novel nutritional approach for promoting healthy ageing.
The Role Of EphA2 Signalling And Environmental Modifiers In Cataract.
Funder
National Health and Medical Research Council
Funding Amount
$591,547.00
Summary
In cataract the clear lens in the eye becomes opaque causing blindness. Cataract is very common in the elderly, but is rarely also seen in babies and children. In babies certain gene defects, and in the elderly the genes and environmental factors contribute to cataract. The EPHA2 gene causes cataract in both young and old people. This project aims to understand how EPHA2 and other related genes cause cataract in young and old people, to prevent, delay or improve its treatment in the future.
Mechanisms Of Proteolysis Of Proteins Containing Oxidised Amino Acids
Funder
National Health and Medical Research Council
Funding Amount
$406,320.00
Summary
There is evidence that during ageing, and age-related diseases, proteins which have been chemically modified by oxidation accumulate in the body, and may have deleterious effects. Oxidation of proteins is a process akin to that by which fats go rancid. It has been demonstrated by the applicants to be an important process in formation of cataracts, and in development of the blood vessel disease, atherosclerosis, which is responsible for most heart attacks and stroke. Other important age-related d ....There is evidence that during ageing, and age-related diseases, proteins which have been chemically modified by oxidation accumulate in the body, and may have deleterious effects. Oxidation of proteins is a process akin to that by which fats go rancid. It has been demonstrated by the applicants to be an important process in formation of cataracts, and in development of the blood vessel disease, atherosclerosis, which is responsible for most heart attacks and stroke. Other important age-related diseases, such as Alzheimer s disease and other neurological disorders, are also claimed to be associated with deranged protein oxidation, and accumulation of oxidised products. There is clear evidence that certain defensive mechanisms, such as those acting to remove invading organisms and clear wounds, are also associated with an enhanced production of oxidised proteins. Perhaps the most important component of defense against oxidised proteins is their removal by complete breakdown to constituent components, and excretion. Normally, the machinery for breakdown of proteins is in vast excess over the required rate of degradation. However, clearly in these conditions of accumulation of oxidised proteins, this is no longer the case, or no longer suffices. Mechanisms by which oxidised proteins are degraded are poorly understood, and quite controversial. Therefore, the present studies bring to bear a new approach to studying this issue, which has been developed by the applicants. The aim is to reveal mechanisms involved in the breakdown of proteins containing oxidised amino acids, both in cellular systems, and in vivo. Such an understanding may allow us to envisage how to remove oxidised proteins by therapeutic means and therefore interfere with the development of age-related diseases such as Alzheimer s disease and cataract formation and the diseases of the blood vessels associated with attack and stroke.Read moreRead less
I am an epidemiologist investigating: 1) the frequency, pathogenesis, risk factors and impacts of common age-related eye disease, particularly focused on the four leading causes of blindness: age-related macular degeneration, cataract, glaucoma and diabetic retinopathy; 2) the potential for screening and clinical diagnostic value of retinal imaging and retinal vascular signs as predictors of major systemic conditions such as hypertension, diabetes and cardiovascular disease.
Age-and Species-related Regulation Of Host Inflammatory Responses In Falciparum And Vivax Malaria
Funder
National Health and Medical Research Council
Funding Amount
$323,640.00
Summary
Malaria kills 1 million people every year, mostly children. The cause of death from malaria differs between children and adults, yet the reason for these differences is unknown. We have shown that in adults regulatory immune cells contribute to malaria disease complications. We want to test if these cells also worsen malaria disease in children. Understanding age-related differences in immune cell regulation will help to improve malaria treatment and aid development of effective malaria vaccines ....Malaria kills 1 million people every year, mostly children. The cause of death from malaria differs between children and adults, yet the reason for these differences is unknown. We have shown that in adults regulatory immune cells contribute to malaria disease complications. We want to test if these cells also worsen malaria disease in children. Understanding age-related differences in immune cell regulation will help to improve malaria treatment and aid development of effective malaria vaccines for adults and children.Read moreRead less
A Population-based Study Of Progression And Risk Factors For Age-related Maculopathy
Funder
National Health and Medical Research Council
Funding Amount
$776,022.00
Summary
Age-related macular degeneration (AMD) is a progressive disease, commencing with the less severe age-related maculopathy (ARM), that ultimately can lead to the loss of fine central vision and personal independence. People with advanced AMD generally retain some mobility if their peripheral vision is maintained, but they are unable to perform tasks such as reading, hobbies or recognising people's faces. Unfortunately, the available treatment for AMD, macular laser photocoagulation, benefits only ....Age-related macular degeneration (AMD) is a progressive disease, commencing with the less severe age-related maculopathy (ARM), that ultimately can lead to the loss of fine central vision and personal independence. People with advanced AMD generally retain some mobility if their peripheral vision is maintained, but they are unable to perform tasks such as reading, hobbies or recognising people's faces. Unfortunately, the available treatment for AMD, macular laser photocoagulation, benefits only a minority of people with this disease. Until safe and effective treatments for AMD can be developed, identification of major risk factors for the development and progression of AMD is essential to determine if interventions aimed at primary prevention can be initiated. This project will expand on the initial findings of the Visual Impairment Project (VIP), a population-based study of age-related eye disease in a cohort of more than 5000 Victorians aged 40 years and older. Data from the VIP have shown that AMD is the most important ophthalmologic public health problem, particularly since AMD is the major cause of vision impairment in Australia and has the least available treatment options. This study will follow individuals who were identified in the VIP with ARM-AMD to determine the natural history and risk factors associated with the longer term progression of AMD. Particular emphasis will be on determining the role of cardiovascular disease risk factors in AMD progression.Read moreRead less
Old age is the main risk factor for atherosclerosis, which is the main cause of mortality and morbidity in the World. We found age-related changes in the microcirculation of the liver called pseudocapillarization that provide a mechanism linking old age with atherosclerosis. Pores in the endothelium called fenestrations disappear, impairing the ability of the liver to breakdown fats. New therapies to treat and prevent age-related pseudocapillarization are being developed.