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The Fetal And Early Childhood Origins Of PCOS: A Prospective Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$499,116.00
Summary
The Polycystic Ovary Syndrome (PCOS) affects up to 10% of women of reproductive age, which translates into around 350,000 women in Australia. It is the most common hormonal disorder in women. The syndrome has far-reaching adverse implications for general and reproductive health, including menstrual disorder, obesity, infertility, miscarriage, pregnancy complications, increased risk of diabetes and possibly heart disease. PCOS also commonly causes cosmetic problems such as excess body hair and ac ....The Polycystic Ovary Syndrome (PCOS) affects up to 10% of women of reproductive age, which translates into around 350,000 women in Australia. It is the most common hormonal disorder in women. The syndrome has far-reaching adverse implications for general and reproductive health, including menstrual disorder, obesity, infertility, miscarriage, pregnancy complications, increased risk of diabetes and possibly heart disease. PCOS also commonly causes cosmetic problems such as excess body hair and acne. The underlying causes of PCOS are not known but are thought to arise during intrauterine (fetal) life and to be modified by aspects of childhood health, particularly overweight and obesity. Using a large and well established cohort of adolescents followed up since fetal life and throughout childhood and currently aged 13-15 years old (the Raine cohort), we will define for the first time the intrauterine and early childhood correlates of PCOS. PCOS will be diagnosed by a specialist gynacologist using current international criteria. We will then utilise extensive existing data from this cohort combined with new measurements on existing samples to determine the contribution of key factors including fetal growth restriction, low birth weight, fetal androgen exposure, rapid postnatal growth, childhood adiposity, elevated fasting glucose and insulin and age at menarche to PCOS. In this way, we will address for the first time the hypothesis that PCOS arises as a result of events during fetal life and is affected by factors during childhood. The results from these studies will improve our understanding of PCOS and eventually improve reproductive and metabolic health for a substantial population of women internationally. It is essential that these studies are conducted as soon as possible or the opportunity will be missed. Girls with persistent menstrual irregularity are likely to be commenced on hormonal treatments which will make the diagnosis of PCOS impossible.Read moreRead less
Elucidating The Mechanism Of Action Of Dendrimer Nanoparticles Against HIV
Funder
National Health and Medical Research Council
Funding Amount
$559,354.00
Summary
Dendrimers are nanoparticles with highly branched structures and they are being developed as topical microbicides to prevent the sexual transmission of HIV. This study will determine how dendrimers block HIV entry into host cells so that we can design more effective inhibitors and microbicides.
The Role Of Chemokines In Establishing HIV Latency
Funder
National Health and Medical Research Council
Funding Amount
$372,049.00
Summary
Although antiviral therapy is effective in controlling HIV, therapy must be continued life-long because the virus cannot be cleared from long lived infected CD4+ T cells that are silently or latently infected. In this proposal we will explore the mechanism of how HIV can enter these resting CD4+ T-cells and establish long lived latent infection. Understanding this process may potentially lead to new strategies to cure HIV infection.
Identification And Characterisation Of Novel Genes For Congenital Cataract
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Cataracts are the leading cause of blindness worldwide. The term describes a clouding of the lens which may lead to visual impairment. Congenital cataracts (present at birth) are less common than age-related cataract but the lifelong impact on vision can be severe, with a third of patients remaining legally blind. Late complications such as aphakic glaucoma may be blinding. We have shown that congenital cataracts are often inherited and have performed a population-based study in South-Eastern Au ....Cataracts are the leading cause of blindness worldwide. The term describes a clouding of the lens which may lead to visual impairment. Congenital cataracts (present at birth) are less common than age-related cataract but the lifelong impact on vision can be severe, with a third of patients remaining legally blind. Late complications such as aphakic glaucoma may be blinding. We have shown that congenital cataracts are often inherited and have performed a population-based study in South-Eastern Australia over the past 5 years to determine the causative genes. A large number of families have been involved in the study and solid progress has been made in identifying mutations in cataract genes and understanding what effect these may have on the patient's prognosis. We have recently identified a new gene in a large Australian family with a syndrome of cataract, mental retardation and teeth problems. This syndrome, known as Nance-Horan syndrome was originally described in Australia 30 years ago and we have worked with the original family to find the exact gene responsible. We already know that this gene causes the same syndrome in other families and in this project we will examine whether it can cause cataract without the other features or mental retardation without cataract. We will perform a series of experiments to learn what this gene does and how it causes the disease. We have also selected 3 other very interesting families with congenital cataracts for further study as we either know already or strongly suspect that they will enable us to identify further new genes for cataract, and in one case mental retardation. Our work in other diseases indicates that understanding the genes in severe young onset cases can give valuable clues to the causes of age-related forms and may in the future enable new ways to prevent and treat the commonest cause of worldwide blindness.Read moreRead less
Impact Of An Infant Sleep Intervention On Infant Sleep And Maternal Wellbeing: A Cluster Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$205,500.00
Summary
Infant sleep problems and postnatal depression are common in the Australian community. Over a third of Australians report a problem with their infant's sleep in the second six months of life whilst 10-15% of Australian women will experience an episode of depression in the first year after their child is born. Both infant sleep problems and postnatal depression have been associated with serious outcomes including child abuse, child behaviour problems, maternal physical and emotional problems, fam ....Infant sleep problems and postnatal depression are common in the Australian community. Over a third of Australians report a problem with their infant's sleep in the second six months of life whilst 10-15% of Australian women will experience an episode of depression in the first year after their child is born. Both infant sleep problems and postnatal depression have been associated with serious outcomes including child abuse, child behaviour problems, maternal physical and emotional problems, family stress and family breakdown. This study builds on previous work conducted by researchers at the Centre for Community Child Health, Royal Children's Hospital, Melbourne. In this work, a brief behavioural intervention significantly decreased infant sleep problems and symptoms of maternal depression, particularly for depressed mothers. The intervention consisted of controlled crying and removal of sleep associations such as a dummy which the infant had become dependent upon to fall asleep. Mothers who received the intervention reported 20% fewer sleep problems and a 45% reduction in depression symptoms compared with mothers who did not receive the intervention. The interention also improved maternal sleep quality and quantity and reduced the need for professional sleep services. It was acceptable to mothers, of low cost and was minimally disruptive to families - in contrast to many current strategies directed primarily at postnatal depression. This trial aims to determine whther a similar intervention delivered by Victorian Maternal and Child health nurses within their usual practice settings can replicate these important benefits.Read moreRead less
Prevalence report by the Australian Advisory Board on Autism Spectrum Disorders (ASD) estimated that 1 child in every 160 children in the 6-12 year-old age group is affected by ASD. There is no cure for ASD and the causes are not understood. We propose that sex hormones may play a role in the development of these disorders. We will test this hypothesis using knockout and transgenic mouse models which have social interaction deficits and brain structure reminiscent of these disorders.
The Role Of The AMPK-ACC2 Signaling Axis In Metabolic Control During Exercise And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$540,973.00
Summary
Australian society is experiencing an epidemic of obesity that is contributing to diabetes, cardiovascular disease and premature death. This project is investigating how exercise might prevent obesity and type 2 diabetes by examining the major pathways that regulate fat metabolism.
Determinant Spreading And The Role Of The MHC Class II Region In Systemic And Organ-specific Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$140,570.00
Summary
Autoimmune diseases are among the most important group of disorders affecting the adult population. In these diseases the immune system damages organs and tissues producing widespread pathology (systemic autoimmunity such as Lupus erythematosus) or localised disease (organ-specific autoimmunity such as insulin dependent diabetes). We understand very little about how and why the immune system attacks the body's own tissues. This study examines how antibodies and T lymphocytes are formed against c ....Autoimmune diseases are among the most important group of disorders affecting the adult population. In these diseases the immune system damages organs and tissues producing widespread pathology (systemic autoimmunity such as Lupus erythematosus) or localised disease (organ-specific autoimmunity such as insulin dependent diabetes). We understand very little about how and why the immune system attacks the body's own tissues. This study examines how antibodies and T lymphocytes are formed against components located inside cells of the body. The study involves genetically modifying mice by introducing key human genes which influence the development of autoimmunity. In this way the role of these human genes can be examined experimentally without having to work exclusively on patients. We also hope that these mice might be important in creating new models of celiac disease and insulin dependent diabetes. The proposed experiments should tell us how these genes contribute to the development of autoimmune disease. This understanding could be relevant devising treatments and interventions to prevent autoimmune diseases.Read moreRead less