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Characterisation Of Human Embryonic Stem Cell Differentiation To Haematopoietic Progenitors And Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$638,856.00
Summary
Blood stem cells, which are found in the bone marrow, are currently used for treating human blood disorders including leukemia and lymphoma. However, for the majority of bone marrow transplant candidates, suitable donors cannot be found. Using embryonic stem cells, this project aims to define the conditions required to generate blood stem cells in the laboratory. The aim of the work is to provide a new source of blood stem cells that could be used in place of donor derived bone marrow.
The Clinical Value Of Serology And Molecular Tests For Diagnosing Invasive Aspergillosis In At-risk Hematology Patients
Funder
National Health and Medical Research Council
Funding Amount
$1,095,500.00
Summary
Aspergillus is a fungus found in soil, on farms and on construction sites. In those whose immune system is impaired it causes severe infection. The people who are particularly at high-risk of Aspergillus infection (called Invasive Aspergillosis) are those with acute leukaemia on chemotherapy or post bone marrow transplantation. Currently 15% of those at high-risk get Invasive Aspergillosis and 58-93% of those infected die. The main reason for this high death rate is that our current diagnostic t ....Aspergillus is a fungus found in soil, on farms and on construction sites. In those whose immune system is impaired it causes severe infection. The people who are particularly at high-risk of Aspergillus infection (called Invasive Aspergillosis) are those with acute leukaemia on chemotherapy or post bone marrow transplantation. Currently 15% of those at high-risk get Invasive Aspergillosis and 58-93% of those infected die. The main reason for this high death rate is that our current diagnostic tests are not good at detecting infection or often only detect the infection at advanced stages when treatment is ineffective. Because of the limitations of current diagnostic tests the current practice is to give empiric antifungal therapy (EAFT) early to treat Invasive Aspergillosis. However studies have demonstrated that this therapy has only resulted in a minor reduction in the mortality rates and it causes significant drug toxicity. It is a suboptimal treatment modality. New tests have been developed to diagnose Invasive Aspergillosis. These tests are for the detection of an Aspergillus protein in blood and for the detection of Aspergillus DNA in the blood. Available data suggests that these new tests are sensitive in the detection of Invasive Aspergillosis. Also other studies suggest that these new tests make an early diagnosis and seem to be able to monitor responses to treatment. However no study has been performed to date which demonstrates that the use of these tests can impact on important patient outcomes. This trial is designed to determine whether the use of the new tests to guide therapy will help improve treatment of Invasive Aspergillosis, reduce drug toxicity and reduce the death rate in the high-risk patients as compared with the current standard method of diagnosis and treatment with EAFT. If the trial is successful then this represents a significant advancement in the treatment and survival of leukaemic and bone marrow transplantation patients.Read moreRead less
Why Is The Bone Marrow A “hot-spot” For Myeloma Plasma Cell Metastasis: Are There Gremlins In The System?
Funder
National Health and Medical Research Council
Funding Amount
$651,979.00
Summary
Most cancer patients die because their cancer spreads from a primary site to other tissues in the body. Once escaping the primary site, 70% of all tumours will spread to bone. This raises the question, why is bone a preferred destination for cancer cells? We provide evidence that Gremlin1, made by non-cancer cells within bone, is a key protein that supports cancer growth. This study will examine whether inhibiting Gremlin1 is a potential therapy to inhibit cancer spreading to bone.
Targeting Bone Marrow Mediated Angiogenesis And Metastasis In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$463,006.00
Summary
Despite advances in treatment and diagnostics breast cancer (BC) remains one of the leading causes of death in women. Metastases and tumour blood vessel recruitment are linked. Work by Dr Mellick and others has shown that host bone marrow contributes endothelial progenitor cells (EPCs) to tumour vasculature. The chemokines and their receptors, which differentiate EPCs from tumour vessels, will be knocked down in the tumour cells and EPC progenitors with the aim of preventing tumour spread.
The Mechanisms Of Epithelial Cell Survival That Govern Thymus Function
Funder
National Health and Medical Research Council
Funding Amount
$620,967.00
Summary
The thymus is an organ dedicated to the production of crucial immune cells, called T lymphocytes. Cancer treatments, such as radiation or chemotherapy, destroy thymic function and impair immune recovery in patients. We aim to uncover molecular processes that govern the life and death decisions of cells in the thymus. Our goal is to then use this information to develop treatments to protect this critical organ from damage and improve immune recovery following radiation or chemotherapy.
Tyrosine Kinase Receptor C-ros-oncogene 1 Mediates Twist-1 Haploinsufficiency Induced Craniosynostosis In Children: A Novel Therapeutic Target
Funder
National Health and Medical Research Council
Funding Amount
$562,863.00
Summary
Children with Saethre-Chotzen syndrome exhibit premature fussed coronal sutures, and other skull/ skeletal malformations. Surgical intervention is the only treatment option to ensure optimal cognitive and skeletal development. Our studies have identified a candidate molecular pathway that regulates bone formation by cranial bone cells from these patients. Targeting these key molecular signalling components with chemical inhibitors will help prevent the premature fusion of cranial sutures.
Gene Mining For Novel Molecular Determinants Of The Skeleton
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
Musculoskeletal conditions affect over 6 million Australians and research has shown that genetic background strongly influences development of these disorders. This project will identify genes that have a role in controlling bone and joint architecture. Identification of these genes will assist in the development of treatments targeting bone disorders and allow screening for these genes to provide an opportunity for people to take preventative action to improve bone and joint health.
Histone Demethylase KDM6A Is A Novel Target For Treating Craniosynostosis In Children With Saethre-Chotzen Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$548,854.00
Summary
Children with Saethre-Chotzen syndrome exhibit premature fused coronal sutures, and other skull/ skeletal malformations. Surgical intervention is the only treatment option to ensure optimal cognitive and skeletal development. Our studies have identified a candidate molecular pathway that regulates bone formation by cranial bone cells from these patients. Targeting this key molecular regulator with chemical inhibitors will help prevent the premature fusion of cranial sutures.
GENETIC PREDICTION OF FRACTURE IN A RISK-STRATIFIED POPULATION
Funder
National Health and Medical Research Council
Funding Amount
$363,000.00
Summary
Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of indivi ....Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of individuals with osteoporosis (e.g., low BMD) did not sustain a fracture, while approximately 60% of fracture cases had BMD above the high risk levels. Thus, BMD alone is not a good discriminant of fracture versus non-fracture cases. It is widely known that the liability to fracture is determined in part by genes. Previous studies, including from our group, have suggested a number of candidate genes that are associated with fracture risk. The fundamental issue that this study is concerned is that how and whether genetic markers could be used to facilitate case finding. It is proposed that common variations of certain genes are associated with fracture risk independent of BMD. That is, they can identify individuals at relatively high and low fracture risk after stratification for BMD. Hence, some markers may identify those individuals likely (and unlikely) to fracture even with low (osteoporotic) BMD. Similarly, some, possibly the same, markers may identify individuals at high risk of fracture despite relatively good (ie non-osteoporotic) BMD. It is further proposed that no single gene will achieve this outcome, but rather a small set of such gene polymorphisms will provide clinically useful risk information. This effect is entirely analogous to the use of clinical risk indicators (eg, age, weight, sex, family history, etc) to assess the risk of future fracture.Read moreRead less
The Role Of Osteocytes In Particle Induced Osteolysis
Funder
National Health and Medical Research Council
Funding Amount
$457,196.00
Summary
Hip replacements often fail due to the loss of adjacent bone. Metal or polyethylene particles are produced as the prosthesis bearing surface wears but how do these particles lead to bone loss? Our work suggests involvement of osteocytes within the bone mineral, which are increasingly understood to drive bone physiology and pathology. We will explore the role of the osteocytes by examining their response to particles, which may identify a new target to prevent particle-induced bone loss.