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Initiation And Diversification Of Systemic Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$200,749.00
Summary
One of the striking findings in autoimmune diseases such as systemic lupus erythematosus and Sjogren's syndrome is the presence in the blood of autoantibodies reacting with certain proteins or autoantigens. The best known autoantigens are termed La and Ro and are important diagnostic markers in these two common conditions. It appears that the immune response starts against Ro and then spreads to La over time, a process known as epitope spreading. There is emerging evidence in Sjogren's syndrome ....One of the striking findings in autoimmune diseases such as systemic lupus erythematosus and Sjogren's syndrome is the presence in the blood of autoantibodies reacting with certain proteins or autoantigens. The best known autoantigens are termed La and Ro and are important diagnostic markers in these two common conditions. It appears that the immune response starts against Ro and then spreads to La over time, a process known as epitope spreading. There is emerging evidence in Sjogren's syndrome that the severity of this condition is related to the degree of epitope spreading to Ro and La, which in turn is controlled by the genetic background of the individual. We therefore wish to study the initiation of the autoimmune response to Ro and the factors which influence spreading or diversification to La, using a mouse model of La-Ro autoimmunity which we have developed. In addition, we shall investigate the potential role of a recently identified gene in a large group of patients with Sjogren's syndrome. We believe this gene may control the epitope spreading and expression of disease. The role of other molecules called chaperones (which bind to Ro) and complement (involved in clearing dead cells which may trigger autoimmunity) will also be studied. The ultimate goal of the work is to develop ways of blocking the epitope spreading which should ameliorate the disase and patients' symtpoms.Read moreRead less
Sjogren's Syndrome As A Disorder Of Anti-receptor Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
A new approach to understanding Sjogren's syndrome Sjogren's syndrome (SS) is a frequent cause of illness predominantly in women, leading to frequent attendances to medical, dental and allied health practitioners. Historically considered a rarity, SS, in both its primary and secondary forms, is arguably the commonest manifestation of human systemic autoimmunity. Increasingly recognised by clinicians as the unifying diagnosis underlying a plethora of chronic disabling symptoms in women from the f ....A new approach to understanding Sjogren's syndrome Sjogren's syndrome (SS) is a frequent cause of illness predominantly in women, leading to frequent attendances to medical, dental and allied health practitioners. Historically considered a rarity, SS, in both its primary and secondary forms, is arguably the commonest manifestation of human systemic autoimmunity. Increasingly recognised by clinicians as the unifying diagnosis underlying a plethora of chronic disabling symptoms in women from the fourth decade and beyond, therapeutic options remain limited due to our primitive understanding of its cause. Emerging evidence suggests that rather than a consequence of physical destruction of salivary and tear glands by cells of the immune system, severe dryness of the mouth and eyes in SS might be caused by antibodies which block the transmission of signals from tiny nerves to receptors in these glands. We also have evidence that other symptoms experienced by patients with SS, including abnormal sweating, irritable bladder and bowel, and Raynaud's phenomenon, may also be the consequence of blockage of nerve supply. Furthermore, we have detected these blocking antibodies in patients with both primary SS and rheumatoid arthritis accompanied by secondary SS, pointing for the first time to a common underlying cause for SS in these two settings. We propose a new approach to understanding Sjogren's syndrome, as a disease of anti-receptor autoimmunity, akin to Graves disease of the thyroid gland. This opens up exciting possibilities for the development of new techniques for the diagnosis and treatment of SS.Read moreRead less
Patient-centred EHealth Approach To Improving Outcomes For Gout Sufferers
Funder
National Health and Medical Research Council
Funding Amount
$688,354.00
Summary
Gout, caused by excessive urate, can be controlled by prescribing medication and patients adhering to them. We will conduct a 2-year controlled trial in primary care to test an eHealth tool to significantly improve gout patient outcomes. This tool tracks patients plasma urate, medication adherence, gout attacks and provides education, interaction with gout experts and reminders of medical visits. Nationwide rollout of this gout management tool will occur after improved outcomes are proven.
DCIS Management Since Publication Of Clinical Practice Recommendations: Surgeons' Practices And Women's Experiences
Funder
National Health and Medical Research Council
Funding Amount
$360,783.00
Summary
Ductal Carcinoma in Situ of the breast (DCIS) now represents 15% of all new cases of breast cancer. Although a benign disease, its diagnosis increases a woman's risk of developing invasive breast cancer and the goal of treatment is prevention of invasive disease. However the characteristics that predict this progression have not been clearly identified. Consequently women are confused about their diagnosis and both clinicians and women are faced with complex treatment decisions. The National Bre ....Ductal Carcinoma in Situ of the breast (DCIS) now represents 15% of all new cases of breast cancer. Although a benign disease, its diagnosis increases a woman's risk of developing invasive breast cancer and the goal of treatment is prevention of invasive disease. However the characteristics that predict this progression have not been clearly identified. Consequently women are confused about their diagnosis and both clinicians and women are faced with complex treatment decisions. The National Breast Cancer Centre (NBCC) published a set of eight clinical practice recommendations for the management of DCIS in September 2003 and a guide for consumers in 2004. Currently there is no information regarding how the treatment recommendations have been received by surgeons, the extent management of DCIS now follows these recommendations or the impact of the treatment recommendations on the medical experiences of women with DCIS. This project will fill this gap. The project aims to: 1. Examine the impact of clinical practice recommendations for the management of Ductal Carcinoma in Situ (DCIS) of the breast on clinical practice 2. Determine awareness of and attitudes towards the recommendations among surgeons treating DCIS and to examine the relationship between these attitudes and clinical practice 3. Examine women's experience of a DCIS diagnosis, their understanding of its prognosis and involvement in treatment decisions after release of a consumer guide in 2004 This research will determine whether the publication of the treatment recommendations in 2003 influenced the medical care women with DCIS recieve and identify the factors associated with surgeons and women that facilitate or prevent the uptake of these recommendations. This information will be used to develop strategies increase surgeons' adoption of the treatment recommendations in order to ensure that all women with DCIS have access to the best care possible.Read moreRead less
Hydatid disease is caused by a parasitic infection that is transmitted to people by animals. The disease causes substantial human morbidity and mortality worldwide, and is endemic in Australia. Currently available drugs are poorly effective against the parasite and treatment of the disease relies mainly on surgical removal of often large parasitic cysts, where this is possible. Blood tests to identify people who are infected rely on the use of parasite samples obtained from animals, which leads ....Hydatid disease is caused by a parasitic infection that is transmitted to people by animals. The disease causes substantial human morbidity and mortality worldwide, and is endemic in Australia. Currently available drugs are poorly effective against the parasite and treatment of the disease relies mainly on surgical removal of often large parasitic cysts, where this is possible. Blood tests to identify people who are infected rely on the use of parasite samples obtained from animals, which leads to difficulties with adequate supply of material and quality control. Research in this laboratory discovered that the hydatid parasite produces a protein that binds the drug cyclosporin A and that specific antibodies are made to this protein in hydatid patients. Preliminary research by others found that cyclosporin A had anti-parasitic effects on hydatid disease in an animal model system. This research project will examine in detail the characteristics of the cyclophilin protein and related proteins, in the hydatid parasite, their interaction with cyclosporin A, the effects of cyclosporin A on the parasite in defined culture conditions, the mechanism by which cyclosporin A exerts anti-parasitic effects and the prospects for use of cyclophilin in tests for the diagnosis of human hydatid disease. The research will contribute to a better understanding of the basic biology of this pathogen and may identify improved methods for the chemotherapy and diagnosis of infection.Read moreRead less
Can unloading footwear improve clinical care of people with knee osteoarthritis? Osteoarthritis is a public health problem imposing major economic and personal burden. It is the fourth highest cause of morbidity in Australia and national health expenditure in 2007 was $2.03 billion. Footwear can reduce knee load which is linked to disease pathogenesis. Specially-designed unloading shoes will be evaluated in a clinical trial and biomechanical studies to determine their efficacy at reducing sympto ....Can unloading footwear improve clinical care of people with knee osteoarthritis? Osteoarthritis is a public health problem imposing major economic and personal burden. It is the fourth highest cause of morbidity in Australia and national health expenditure in 2007 was $2.03 billion. Footwear can reduce knee load which is linked to disease pathogenesis. Specially-designed unloading shoes will be evaluated in a clinical trial and biomechanical studies to determine their efficacy at reducing symptoms, mechanical mechanism of pain relief, patient sub-groups that best respond to treatment and whether combined treatment with medial arch supports changes knee biomechanics. Outcomes will impact clinical practice and relieve suffering of people with knee osteoarthritis. Findings will also guide future shoe developments for arthritis. Read moreRead less
Genetic Dissection Of The Biogenesis And Function Of Type IV Fimbriae Of Pseudomonas Aeruginosa
Funder
National Health and Medical Research Council
Funding Amount
$407,545.00
Summary
Pseudomonas aeruginosa is a common bacterium which causes serious life-threatening infections of individuals with cystic fibrosis, AIDS or who have suffered severe burns or are undergoing cancer chemotherapy. This pathogen, and a number of other important infectious bacteria use surface filaments, called fimbriae, like grappling hooks to attach to the cells of the body and to move across host tissues. These fimbriae are produced in response to environmental conditions, and are assembled by a pro ....Pseudomonas aeruginosa is a common bacterium which causes serious life-threatening infections of individuals with cystic fibrosis, AIDS or who have suffered severe burns or are undergoing cancer chemotherapy. This pathogen, and a number of other important infectious bacteria use surface filaments, called fimbriae, like grappling hooks to attach to the cells of the body and to move across host tissues. These fimbriae are produced in response to environmental conditions, and are assembled by a process that is also used in the export of toxins and other pathogenic molecules. This project will characterise genes which specify and control this system, as a means to design better treatments against such bacteria, many of which are resistant to antibiotic treatment.Read moreRead less