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Endothelial Dysfunction As A Therapeutic Target In Severe Malaria
Funder
National Health and Medical Research Council
Funding Amount
$842,329.00
Summary
Even with very best drugs to kill malaria parasites, over 15% of patients with severe malaria still die. Their blood vessels are clogged up by malaria parasites. We have shown that the cells lining their blood vessels can't make enough nitric oxide to keep them non-sticky and allow blood through. We want to test whether giving arginine can 1) increase nitric oxide, 2) open up the clogged blood vessels and 3) dampen down other processes that clog up blood vessels in severe malaria.
Targeted Inhibition Of Polyamine Synthesis For Treatment Of Childhood Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$576,605.00
Summary
The childhood cancer, neuroblastoma, frequently has a dismal outcome despite the use of intensive therapy. Polyamines are molecules that are essential for cell survival and these are increased in aggressive neuroblastoma. Using pre-clinical models, we have shown that inhibiting polyamine production can significantly delay neuroblastoma growth. This project aims to improve the overall efficacy of this treatment by targeting multiple steps in polyamine synthesis in combination with chemotherapy.
Wnt-5a Signalling - A Novel Therapy For Triple Negative And Tamoxifen Resistant Breast Cancer Patients
Funder
National Health and Medical Research Council
Funding Amount
$330,534.00
Summary
Breast cancer is the most common cancer in women. Commonly used drugs target the estrogen receptor (ER). However, one third of breast cancer patients lack ER, and do not respond to treatment. Cancers that lack ER also lack a gene called Wnt5a, which is linked to better prognosis. We have shown that fixing Wnt5a can restore ER allowing cells to respond to Tamoxifen. We would now test this in animals, in the hope of developing a new drug for breast cancer patients currently with limited options.
Nuclear Functions Of Dengue NS5 Protein: Role In Disease
Funder
National Health and Medical Research Council
Funding Amount
$736,953.00
Summary
Our work indicates that the NS5 protein from Dengue virus (DV) has distinct sequences that enable it to traffic into and out of the host cell nucleus to exert pathogenic effects on transcription and thereby impair the host cell anti-viral and immune responses. We aim to characterise these properties in detail, and demonstrate their importance to DV pathogenicity using a novel animal model of the disease.
The Mechanism Of Action Of IVIg In Inflammatory Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$452,141.00
Summary
Intravenous immunoglobulin (IVIg) is the major therapy used for the inflammatory neuropathies GBS, CIDP and for multifocal neuropathy. The cost of IVIg for these neuropathies in Australia is approximately 60 million dollars per year. As new indications for IVIg continue to be developed the resource becomes more valuable. We plan to explore the mechanism of action of IVIg with the aim of saving this precious resource and providing significant financial savings to the health service.
Inhibition Of Bone Resorption Increases Skeletal Mechanical Strength By Thickening Trabecular Structures
Funder
National Health and Medical Research Council
Funding Amount
$175,648.00
Summary
This project will identify the basis by which a number of therapies for osteoporosis decrease the risk of bone fractures. Currently at least four classes of these compounds in current use for the treatment of osteoporosis. Some of them have been found to have a very marked beneficial effect by halving the risk of fracture. This study will determine if each of these classes of compounds have the ability to increase the mechanical strength of bone to the same level and if each of these compounds h ....This project will identify the basis by which a number of therapies for osteoporosis decrease the risk of bone fractures. Currently at least four classes of these compounds in current use for the treatment of osteoporosis. Some of them have been found to have a very marked beneficial effect by halving the risk of fracture. This study will determine if each of these classes of compounds have the ability to increase the mechanical strength of bone to the same level and if each of these compounds has the same effects on bone structure. Further the effects of stimulating bone formation by subjecting the skeletal to mechanical stress, on the efficacy of each of the therapies will be established. Conversely the effect of aging, which imposes a limitation on bone formation, will be studied.Read moreRead less
Two Recently Identified Calcium Transporters In Lactation And During Mammary Epithelial Cell Apoptosis.
Funder
National Health and Medical Research Council
Funding Amount
$465,115.00
Summary
The transport of calcium into milk is a key event in human health. In addition to its importance in neonatal nutrition, the way breast cells regulate calcium also has implications in breast cancer, as well as the modification of proteins important in immunity, and the activity of biopharmaceuticals. This grant will determine how two specific calcium transporters regulate calcium levels in the breast and their respective roles in cellular processes important in normal function and in disease.
Tailored Treatments For Premenopausal Patients With Endocrine Responsive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$257,250.00
Summary
For women under 50 years with hormone receptor positive (ER+) breast cancer, adjuvant treatment with chemotherapy, tamoxifen and ovarian ablation are each effective and reduce recurrence. Combining two treatments is more effective than one, although it is uncertain if combining three provides extra benefit. Ovarian ablation by surgery or radiation is permanent, but reversible ovarian suppression by injections is now available. Three international trials called SOFT, TEXT and PERCHE have been des ....For women under 50 years with hormone receptor positive (ER+) breast cancer, adjuvant treatment with chemotherapy, tamoxifen and ovarian ablation are each effective and reduce recurrence. Combining two treatments is more effective than one, although it is uncertain if combining three provides extra benefit. Ovarian ablation by surgery or radiation is permanent, but reversible ovarian suppression by injections is now available. Three international trials called SOFT, TEXT and PERCHE have been designed for adjuvant therapy of premenopausal women with ER+ breast cancer. These trials take into account regional-country variations in medical practice and different patient choices in this setting. SOFT is for very young women and tests the benefit of adding ovarian suppression in a woman who has received chemotherapy, with tamoxifen planned, but who has not gone into menopause after chemotherapy. The trial also tests if substituting a newer drug called exemestane for tamoxifen, combined with ovarian function suppression is more effective. TEXT is for women who would ordinarily be treated with ovarian suppression plus tamoxifen. The TEXT trial also tests substitution of exemestane for tamoxifen. Exemestane is an aromatase inhibitor. Aromatase inhibitors lower oestrogen levels, but only work if the ovaries are inactive. Recent trials in post menopausal women show aromatase inhibitors are more effective than tamoxifen, and we aim to replicate that improvement in younger women by combining exemestane with ovarian suppression. PERCHE is for women in whom the benefit of chemotherapy is uncertain, for example those with limited or no spread to lymph nodes. All women receive combined endocrine treatment with ovarian suppression plus tamoxifen, and are randomised to receive in addition, either chemotherapy or no chemotherapy, to see if results differ.Read moreRead less
Tailored Treatments For Premenopausal Women With Endocrine Responsive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$299,213.00
Summary
For women <50yrs with ER+ breast cancer adjuvant treatment (AT) with chemotherapy (CT), tamoxifen and ovarian function suppression (OFS) are each effective and reduce recurrence. Combining 2 treatments is more effective than 1, but it is unclear if combining 3 provides any extra benefit. 2 trials,SOFT and TEXT, aim to answer this question. SOFT tests the benefit of adding OFS for very young women who remain premenopausal after CT, TEXT is for women who should receive OFS from the start of AT.
Regulatory Mechanisms Of Antibody Cytotoxicity For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$566,087.00
Summary
Use of antibodies for cancer therapy, where a protein is made in the laboratory to recognize and act on cancer cells that have a target antigen, has emerged as an important therapeutic area in oncology. The lewis-y (Ley) antigen is found in over 70% of epithelial cancers. We have developed an antibody against Ley (hu3S193) which can target cancer cells. Our research is aimed at developing optimal cancer cell killing by our anti-Ley antibody.