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GM-CSF Regulation Of Preimplantation Embryo Development
Funder
National Health and Medical Research Council
Funding Amount
$481,320.00
Summary
Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be ov ....Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be overcome simply by the transfer of a single embryo. However, patient and clinical expectations are that single embryo transfer should be achieved with little to no reduction in pregnancy rate, and currently this is not possible because our methods for culturing embryos are inadequate. Studies in animals suggest that laboratory growth of mammalian embryos can lead to small-for-gestational age babies (even when the effect of multiple births is taken into consideration). This backed by recent studies which agree that babies born from IVF are smaller than expected. This might lead to health problems in later life, as smallness at birth is associated with higher risks of cardiovascular disease and diabetes, especially as age progresses beyond 40 years. However, the oldest IVF child is currently 23 years of age. Previously we have shown that a protein growth factor, called granulocyte-macrophage colony-stimulating factor (GM-CSF), found normally in the reproductive tract, has dramatic beneficial effects on human and mouse embryos grown in the laboratory. Furthermore, we have shown in mice that embryo exposure to GM-CSF alleviates the detrimental side effects of in vitro culture on foetal growth and body structure after birth. Our research is now focussed on understanding why this protein is beneficial to embryo growth and to test if we can increase pregnancy rates and produce normal healthy infants from the transfer of single embryos treated with GM-CSF.Read moreRead less
Cellular And Molecular Mechanisms Of Transcutaneous Immunisation
Funder
National Health and Medical Research Council
Funding Amount
$190,490.00
Summary
Vaccines are among the most effective medical interventions. The recent discovery that cholera toxin, when applied to the normal skin of humans and laboratory animals, stimulates powerful and protective immune responses to itself, and to other proteins has opened up the possibility of needle-free vaccines in the form of skin patches. How CT brings about this effect is currently unknown. We have discovered that the immune stimulating effect of CT depends upon the production of an immune protein ( ....Vaccines are among the most effective medical interventions. The recent discovery that cholera toxin, when applied to the normal skin of humans and laboratory animals, stimulates powerful and protective immune responses to itself, and to other proteins has opened up the possibility of needle-free vaccines in the form of skin patches. How CT brings about this effect is currently unknown. We have discovered that the immune stimulating effect of CT depends upon the production of an immune protein (cytokine) called tumour necrosis factor (TNF). TNF is known to activate specialised immune cells within the skin (Langerhan's Cells ) and we hypothesise that the interaction beween CT and LC via TNF is the pathway to the potent immune response. In this project we propose to investigate the cells and molecules involved in the immune effects of CT in the skin with a view to the development of new skin based vaccine strategies.Read moreRead less
Preclinical Development Of A Humanised Antibody To C5aR.
Funder
National Health and Medical Research Council
Funding Amount
$124,875.00
Summary
Complement factor C5a is one of the most potent inflammatory mediators in the body. We have developed a monoclonal antibody that blocks the C5a receptor in vitro, and completely shuts down disease in a mouse model of rheumatoid arthritis. We plan to develop this promising new antibody into a potent therapy to treat a range of chronic and acute inflammatory diseases. The antibody has been humanised and this will be tested in three models of inflammation (rheumatoid arthritis, sepsis and colitis) ....Complement factor C5a is one of the most potent inflammatory mediators in the body. We have developed a monoclonal antibody that blocks the C5a receptor in vitro, and completely shuts down disease in a mouse model of rheumatoid arthritis. We plan to develop this promising new antibody into a potent therapy to treat a range of chronic and acute inflammatory diseases. The antibody has been humanised and this will be tested in three models of inflammation (rheumatoid arthritis, sepsis and colitis) to determine the efficacy of the antibody, safety, the most effective dose, timing and route of administration. These studies are a necessary prelude to human clinical trials, which we hope to perform in approximately 24 months.Read moreRead less
Development Of Anti-CXCR2 Monoclonal Antibodies For Tumour Therapy
Funder
National Health and Medical Research Council
Funding Amount
$174,867.00
Summary
New therapies to treat cancers and inflammatory diseases are urgently required. Our aim is to develop a new treatment for cancer and inflammation, by blocking the chemokine receptor CXCR2 which is central to angiogenesis (blood vessel growth) and inflammation. We have produced a highly effective monoclonal antibody (mAb) inhibitor of CXCR2, that is suitable for preclinical and clinical development. The project aims to examine the efficacy of this mAb in mouse tumour models and inflammation.
Ocular Implant For The Treatment Of Bacterial Endophthalmitis
Funder
National Health and Medical Research Council
Funding Amount
$483,446.00
Summary
We seek to develop an ocular implant for the treatment of bacterial endophthalmitis. The implant will be a small device that can be administered directly to the affected ocular cavity to release an antibiotic in a controlled manner to clear any infection. The implant will erode and leave no residue. It will be produced from a novel drug-polymer conjugate technology that allows polymer devices that comprise >50% drug to be made.
Development And Evaluation Of Novel Anti-inflammatory Products Derived From An Indigenous Medicinal Plant
Funder
National Health and Medical Research Council
Funding Amount
$276,598.00
Summary
This collaborative project between researchers at the University of South Australia and Indigenous traditional owners from Northern Kaanju homelands (Cape York Peninsula, Qld) will develop and evaluate products derived from the Northern Kaanju medicinal plant Dodonaea polyandra. Extracts of the plant and novel compounds isolated from it have anti-inflammatory activity. These have the potential to be used in inflammatory diseases such as dermatitis, arthritis and inflammatory bowel disease.
Development Of Inhibitors Of PKCzeta For Targeting Vascular Leak
Funder
National Health and Medical Research Council
Funding Amount
$335,113.00
Summary
Vascular leak (permeability) is a chief pathophysiological mechanism of many inflammatory diseases and cancer. Effective methods of reducing vascular permeability are likely to reduce or prevent morbidity. At present there are no potent broad spectrum inhibitors of vascular permeability. This application focuses on the development of such inhibitors.
Development Of Anti-CXCR7 MAbs For The Treatment Of Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$399,998.00
Summary
Fibrosis is a serious biological process that occurs in many disease conditions, including cancer, inflammation and infections. We have produced antibodies to CXCR7, and these antibodies completely inhibit fibrosis in a mouse model. We plan to develop these antibodies in to a suitable drug for human clinical trials.
Protease Activated Receptor 2 Antagonist In Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$621,347.00
Summary
The immune response to infection involves a network of proteins that produce an inflammatory response. Sometimes this response is prolonged or uncontrolled and can lead to a large number of inflammatory and other diseases. We have discovered a class of drugs that can bind to a particular protein on the surface of human cells and control this inflammatory response. This property has the potential to treat a wide range of inflammatory and other diseases in humans.