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A National Resource For Mouse Models Of Mesothelioma
Funder
National Health and Medical Research Council
Funding Amount
$483,643.00
Summary
Mouse models of mesothelioma have led to a greater understanding of the disease and the identification of potential drug therapies some of these have now been translated into clinical trials. In the existing models, mesothelioma cells that have been grown in the laboratory are transplanted into animals by injecting the cells under the skin. Different cell lines with different properties are used in different experimental protocols. This application will fund the establishment of a central resour ....Mouse models of mesothelioma have led to a greater understanding of the disease and the identification of potential drug therapies some of these have now been translated into clinical trials. In the existing models, mesothelioma cells that have been grown in the laboratory are transplanted into animals by injecting the cells under the skin. Different cell lines with different properties are used in different experimental protocols. This application will fund the establishment of a central resource to maintain and distribute these cell lines. In addition, we describe a new transgenic mouse model in which mesotheliomas are rapidly induced in the peritoneal cavity after exposure to asbestos, recreating the natural tumour development much more accurately. These mice have been engineered to express the cancer causing protein of a monkey virus (SV40 large T antigen) in their mesothelial cells because it has been suggested that the virus has a role in the development of mesothelioma. This application also seeks funding to use the MexTAg mice to test the usefulness of different therapies for the prevention or treatment of mesothelioma. These animals give us the ability to investigate the disease in a more realistic environment than previous models. In parallel collaborative studies with other groups investigating different aspects of the biology of this cancer, we plan to analyze the earliest changes in the development of the disease and search for early markers using proteomics and gene expression studies. We anticipate that this model will generate information more directly relevant to understanding the human disease and will provide essential experimental data for clinical trials.Read moreRead less
In type 1 diabetes the body becomes deficient in insulin production from pancreatic b cells because the immune system mistakenly attacks and destroys b cells as if they were an invading infection. Recurrence of autoimmune destruction of b cells also occurs following transplantation of whole pancreas or islet cells and may occur in the future when other engineered insulin producing cells are transplanted. The focus of this program is to better understand how b cells are killed by the immune syste ....In type 1 diabetes the body becomes deficient in insulin production from pancreatic b cells because the immune system mistakenly attacks and destroys b cells as if they were an invading infection. Recurrence of autoimmune destruction of b cells also occurs following transplantation of whole pancreas or islet cells and may occur in the future when other engineered insulin producing cells are transplanted. The focus of this program is to better understand how b cells are killed by the immune system and to test ways of protecting beta cells from these mechanisms. Because of the inaccessibility of the pancreas to study (particularly biopsy) in humans with diabetes, much of the proposed work will be carried out in b cells derived from non-obese diabetic (NOD) mice, the best available mouse model of type 1 diabetes. It is clear from the literature that a molecule called perforin found in cytoxic T lymphocytes (CTL) is a major, if not the major, mechanism the immune system uses against b cells. For this reason we will try to better understand the interaction between b cells and perforin and ultimately design ways of them from perforin-mediated cell death. It is equally clear that there are other mechanisms besides perforin that can cause b cell death and the program will also address discovery of these mechanisms and new ways to block them. Beta cells in NOD mice will be protected from perforin or other mechanisms by the addition of protective genes or removal of harmful genes using transgenic knockout technology. Addition or removal of genes involved in cell death can be done systematically and each protocol tested using NOD mouse model. The process of cell death that b cell undergo in type 1 diabetes is called apoptosis. Apoptosis is a general mechanism by which cells of all types die. Experts in the biology of apoptosis and perforin are important members of the program, providing the opportunity to translate the latest advances in cell death research to diabetes. This research addresses several of the specific research areas of interest to JDRF. It focuses on the prevention of b cell death in individuals with type 1 diabetes receiving islet transplants. It may be applicable in the future to protection of stem or precursor cells that have been differentiated into b cells or even to devising strategies to prevent the development of diabetes.Read moreRead less
Osteoporosis is a common condition in which bone strength is reduced due to reduced amount and quality of bone. Reduced bone strength means an increased risk of fracture. Osteoporotic fractures occur in 1 in 2 women and 1 in 3 men in their lifetime, and the likelihood of suffering osteoporotic fracture increases with age. Most of the risk of developing osteoporosis is genetic, but few of the genes involved have been identified. Our goal is to identify those genes. We will complete recruitment an ....Osteoporosis is a common condition in which bone strength is reduced due to reduced amount and quality of bone. Reduced bone strength means an increased risk of fracture. Osteoporotic fractures occur in 1 in 2 women and 1 in 3 men in their lifetime, and the likelihood of suffering osteoporotic fracture increases with age. Most of the risk of developing osteoporosis is genetic, but few of the genes involved have been identified. Our goal is to identify those genes. We will complete recruitment and assessment of a cohort of 1500 postmenopausal women with either low or high bone mineral density from pre-existing population cohorts in Australia. A genomewide association study will then be performed on these cases. Associated genes in different datasets will then be investigated further in our cohort, and high-density SNP mapping performed to identify true associated variants. These studies should identify most genetic variants associated with BMD variation and low trauma fracture in the general community, allowing development of diagnostic-disease predictive genetic tests, and informing development of novel therapeutic agents for osteoporosis.Read moreRead less
Gene Based Treatment Strategies For Diabetic Retinopathy
Funder
National Health and Medical Research Council
Funding Amount
$2,630,000.00
Summary
Diabetic retinopathy is the leading cause of blindness in the working population of developed countries and it is an increasing problem in the developing world. Present therapy involves extensive laser destruction of the light-detecting part of he retina. In addition, it is not only effective when administered at an appropriate stage in the disease process. Consequently, there is an urgent need for the development of better, prophylactic, easily administrable and cheaper therapies. This project ....Diabetic retinopathy is the leading cause of blindness in the working population of developed countries and it is an increasing problem in the developing world. Present therapy involves extensive laser destruction of the light-detecting part of he retina. In addition, it is not only effective when administered at an appropriate stage in the disease process. Consequently, there is an urgent need for the development of better, prophylactic, easily administrable and cheaper therapies. This project aims to develop a potentially permanent solution to alleviate diabetes-related blindness in the world. The project combines several very recent scientific advances into one strategy to combat diabetic retinopathy at a molecular level. Vision is our most important sensory organ that cannot be replaced. Thus, human trials can only be conducted following extensive animal safety and efficacy trials. To date the development of new therapies has been seriously hampered by the lack of appropriate, easy to reproduce animal models for different stages of diabetic retinopathy. In addition, it aims to identify new therapeutic agents from molecules that are naturally produced by the retina while fighting the disease. Finally, tested and evaluated in the animal models. The most successful therapeutic candidates will then be further developed for human trials.If successful, our approach will potentially have a major impact on the treatment of diabetic retinopathy and possibly on all diabetic vascular diseases. A single injection might only be necessary to prevent the development of diabetic retinopathy, which would represent a significant weapon in the management of patients. In addition, successful application of secretion gene therapy in the eye might open up the possibility to introduce the same concept for the treatment of larger organs undergoing microvascular changes as a result of diabetes.Read moreRead less
A Randomised Controlled Trial Of The Cost-effectiveness Of Supportive Care Coordination For Advanced Cancer
Funder
National Health and Medical Research Council
Funding Amount
$147,269.00
Summary
The study will test the cost-effectiveness of two models of supportive care coordination for advanced cancer against usual care: a Telephone Caseworker model and an Oncologist-GP model. Both models are aimed at improving patients' and their informal caregivers' health and psychosocial status; are patient-centred, evidence based and readily transferable across health care settings. The Telephone Caseworker model has the additional advantage of reaching people isolated through geography, physical ....The study will test the cost-effectiveness of two models of supportive care coordination for advanced cancer against usual care: a Telephone Caseworker model and an Oncologist-GP model. Both models are aimed at improving patients' and their informal caregivers' health and psychosocial status; are patient-centred, evidence based and readily transferable across health care settings. The Telephone Caseworker model has the additional advantage of reaching people isolated through geography, physical disability or age.Read moreRead less
Development Of A Palliative Care Service For Rural And Remote Communities
Funder
National Health and Medical Research Council
Funding Amount
$150,000.00
Summary
This project will develop, implement and evaluate a new model of providing palliative care to individuals in rural and remote communities that will utilise existing health and community resources to provide palliative care. As the number of patients requiring palliation in rural and remote communities is small, the service may not function at all times but come together (pop-up) as required. Evaluation of the model in three different types of rural communities will be undertaken in three states ....This project will develop, implement and evaluate a new model of providing palliative care to individuals in rural and remote communities that will utilise existing health and community resources to provide palliative care. As the number of patients requiring palliation in rural and remote communities is small, the service may not function at all times but come together (pop-up) as required. Evaluation of the model in three different types of rural communities will be undertaken in three states (New South Wales, Queensland and West Australia). Phase I will develop a framework to assist rural communities undertake a critical palliative care service review. Phase II will implement and evaluate the model, leading to recommendations for provision of best practice palliative care more generally in rural communities.Read moreRead less
Confirming The Burden Of Disease Associated With Dementia Using New Empirically Driven Australian Based Disability Rati
Funder
National Health and Medical Research Council
Funding Amount
$138,084.00
Summary
The amount of burden the population experiences as a result of individual diseases influences health policy. The Australian Burden of Disease project quantifies the relative burden associated with each disease. New estimates are to be released this year will outline the magnitude of burden associated with dementia now and estimate that for the year 2023. Although the projections use the best data available, three improvements to the methodology would improve the accuracy of the dementia burden e ....The amount of burden the population experiences as a result of individual diseases influences health policy. The Australian Burden of Disease project quantifies the relative burden associated with each disease. New estimates are to be released this year will outline the magnitude of burden associated with dementia now and estimate that for the year 2023. Although the projections use the best data available, three improvements to the methodology would improve the accuracy of the dementia burden estimates. First, the dementia calculations currently use a “disability weight” metric derived from a Dutch study. This is problematic in that the weights do not reflect an Australian experience of dementia, nor do they reflect the preferences of people closely affected by the disease (e.g. carers). Second, the dementia estimates do not include cases of mild cognitive impairment (considered a precursor state of dementia). Hence the dementia estimates may not estimate the full impact of dementia in Australia. Finally, there is no evidence that the method used by the Burden of Disease study to account for the impact of disease comorbidity adequately deals with the comorbidity associated with dementia. Consequently, there is need to develop a new and comprehensive set of disability weights for dementia that are Australian-based, include all stages of dementia severity and account for comorbidity. The proposed project aims to develop a new set of empirically derived Australian-based disability weights for dementia. The project will entail three studies. The first study will generate empirically based case vignettes that describe a range of dementia case scenarios. These descriptions will then be used in rating exercises (Study 2) to develop new disability weights. The second study involves Australian health practitioners, carers and lay persons reading case vignettes and completing health valuation rating exercises to generate new disability weights for dementia. The third study uses the new disability weights to re-calculate the burden of disease estimates for dementia. The new estimates will be compared to those reported by the 2007 Australian Burden of Disease project. In knowing the accuracy of the estimates, policy makers can use the burden data for dementia with confidence when engaging in service planning for the future.Read moreRead less
Identifying EHealth Literacy And Readability Issues For Palliative Care Consumers
Funder
National Health and Medical Research Council
Funding Amount
$29,375.00
Summary
Access and use of health information can affect a patient’s health experience and potentially their health outcomes. Increasingly health information is being provided and sought through the internet and online resources. Palliative care patients and their carers have specific information needs relating to the nature and progress of their disease, their symptoms and their current and pending quality of life. However, their ability to find and use information relies on many factors such as individ ....Access and use of health information can affect a patient’s health experience and potentially their health outcomes. Increasingly health information is being provided and sought through the internet and online resources. Palliative care patients and their carers have specific information needs relating to the nature and progress of their disease, their symptoms and their current and pending quality of life. However, their ability to find and use information relies on many factors such as individual skills and experiences and how information is presented and made available. eHealth literacy is a measure of the mix of skills required by consumers to successfully access and understand palliative care information. Readability is one aspect of eHealth literacy and readability scales can be used to identify how effective websites are in providing appropriate written information for palliative care consumers. This research will help assess eHealth literacy levels and hence potential intervention needs of palliative care patients and carers as well as determining whether the readability requirement of palliative care websites and information is too high.Read moreRead less