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Unconventional Mechanisms For Activating The NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$747,031.00
Summary
Many inflammatory driven diseases such as arthritis, atherosclerosis and septic shock are also associated with cell death. This project will identify, at the molecular level, how cell death signalling specifically acts to trigger pathological inflammation. As such, it will identify novel targets for the development of next generation anti-inflammatory drugs.
S100A8/A9 As A Target In Metabolic Diseases To Inhibit The Acceleration Of Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$554,990.00
Summary
Obesity and diabetes are the leading cause of premature death, due to accelerated cardiovascular disease (CVD). The abundance of blood monocytes influences the progression and regression of CVD. We discovered that S100A8/A9 promotes monocyte production in obesity and diabetes. This project will explore how S100A8/A9 is produced in diabetes and obesity and if blocking its function using a novel drug will prevent obesity and diabetes associated CVD.
Macrophage Polarisation And Control Of Pulmonary Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$895,494.00
Summary
As key immune cells, macrophages are polarised to phenotypes that turn inflammation on or off. In cystic fibrosis, defective macrophage polarisation enhances inflammation and prevents lung repair. We are defining the molecules and cellular pathways that control this process and identifying targets for existing drugs that can be used to reprogram macrophages and restore lung repair to improve patient outcomes.
A New Master Adaptor Protein For Toll-like Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$869,288.00
Summary
Certain proteins on the surface of cells are able to sense danger and infection. These receptors use adaptor proteins to enable cells to respond appropriately. We have discovered a new adaptor that controls receptor signalling in inflammation. This new master adaptor likely has widespread roles in infection and inflammation. We aim to understand how this adaptor works, and to identify ways of blocking its actions. These studies may help us to control inflammation underpinning many diseases.
Innate Immune Signalling In Mycobacterium Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$562,857.00
Summary
Tuberculosis (TB) is a major global health threat that causes 1.5 million deaths every year. This study will characterise a new molecular control mechanism that optimises the immune response to the bacteria that cause TB and determine how it contributes to controlling the infection. Such knowledge is essential to help improve patient management and develop better treatments for this devastating disease.
Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$583,477.00
Summary
Ross River virus and chikungunya virus cause muscle and joint pain that can persist for a long time. This project looks at factors in the human host that affect the disease severity, with the aim of finding new treatments.
New Treatments For Epitheliod Inflammatory Myofibroblastic Sarcoma
Funder
National Health and Medical Research Council
Funding Amount
$647,267.00
Summary
Epithelioid Inflammatory myofibroblastic sarcoma (eIMS) is a rare aggressive cancer, most common in of childhood and young adults. This cancer has been scarcely studied due to its rarity and is not cured by standard chemotherapeutic regimes. Our investigations will extensively characterise eIMS samples from recently diagnosed patients, and apply a new laboratory model to discover more effective drugs and improve treatment outcomes.
How IsomiRs Expand The MicroRNA Functional Repertoire In Affecting Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$439,570.00
Summary
MicroRNAs function as regulators of gene expression. It is becoming appreciated that microRNAs are frequently expressed as variants with subtly different sequences. We find here that variation in one important cancer-associated microRNA, miR-222, promotes differences in the behaviour of cells expressing them. This work seeks to understand how microRNA variation confers such properties to cells, to identify the genes miR-222 variants regulate, and to examine how widespread it is that microRNA var ....MicroRNAs function as regulators of gene expression. It is becoming appreciated that microRNAs are frequently expressed as variants with subtly different sequences. We find here that variation in one important cancer-associated microRNA, miR-222, promotes differences in the behaviour of cells expressing them. This work seeks to understand how microRNA variation confers such properties to cells, to identify the genes miR-222 variants regulate, and to examine how widespread it is that microRNA variation contributes to cancer.Read moreRead less
Unlocking Hidden Cancer Drivers Using Transcriptome Data
Funder
National Health and Medical Research Council
Funding Amount
$700,473.00
Summary
New sequencing technologies allow us to get an unbiased look at the molecular signalling in a tumour. However this information is very complex and need specialised methods in statistic and computation in order to make new discoveries. Here will will develop analysis methods to find novel transcriptional variants in cancer and then test them in the lab in order to understand if our discoveries are responsible for causing cancer.
Plasmin is a complex enzyme that performs major roles in removal of blood clots, wound healing and in tumor metastasis. Here we will understand how plasmin function is regulated at the molecular level. These key insights will be of future use in the development of therapeutics targeting the plasmin system in cancer and clotting diseases.