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Dynamics of mitochondrial cristae in life and death . This application seeks to use innovative approaches to address how massive structural arrangements in mitochondria are dealt with during normal cell function, and modulated during cell death. The study builds on discoveries made by a team with world-leading expertise in mitochondrial biology and cell death – and brings innovative, cutting-edge techniques in cell biology, proteomics and imaging. The findings will provide new fundamental insig ....Dynamics of mitochondrial cristae in life and death . This application seeks to use innovative approaches to address how massive structural arrangements in mitochondria are dealt with during normal cell function, and modulated during cell death. The study builds on discoveries made by a team with world-leading expertise in mitochondrial biology and cell death – and brings innovative, cutting-edge techniques in cell biology, proteomics and imaging. The findings will provide new fundamental insights into cellular organisation and uncover new principles of communication. Trainees will gain skills in technologies that are highly translatable and in demand in other areas of scientific endeavours. As such the expertise obtained will expand Australian research capabilities.
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Understanding T cell trafficking and function during antigenic interference. Science generally studies antigenic stimulation in isolation, by measuring immunity towards antigens derived from a single pathogen. However, as mammals can harbour more than one infection at any given time, we established a model of antigenic interference using different antigens derived from two unrelated pathogens, influenza A (IAV) and Semliki Forest virus (SFV). Our data show that prior exposure to either IAV or SF ....Understanding T cell trafficking and function during antigenic interference. Science generally studies antigenic stimulation in isolation, by measuring immunity towards antigens derived from a single pathogen. However, as mammals can harbour more than one infection at any given time, we established a model of antigenic interference using different antigens derived from two unrelated pathogens, influenza A (IAV) and Semliki Forest virus (SFV). Our data show that prior exposure to either IAV or SFV greatly perturbs T cell dynamics. This proposal will study, at cellular and molecular levels, T cell trafficking, function and clonal distribution during antigenic interference, thus advance fundamental knowledge on T cell immunity during antigenic competition, and provide a new paradigm on how we research T cell immunity.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100830
Funder
Australian Research Council
Funding Amount
$464,928.00
Summary
Elucidating the genesis of MAIT cell-mediated immunity. T cells develop in the thymus and proceed to survey our body probing molecules that signal if anything is abnormal. A specialised subset of T cells, mucosal associated invariant T (MAIT) cells are crucial in detecting microbial molecules and infection, yet their numbers vary widely between individuals. A key problem is that the factors controlling their development and function are poorly understood. This proposal aims to decode this critic ....Elucidating the genesis of MAIT cell-mediated immunity. T cells develop in the thymus and proceed to survey our body probing molecules that signal if anything is abnormal. A specialised subset of T cells, mucosal associated invariant T (MAIT) cells are crucial in detecting microbial molecules and infection, yet their numbers vary widely between individuals. A key problem is that the factors controlling their development and function are poorly understood. This proposal aims to decode this critical issue in MAIT cell biology, using innovative tools to investigate the molecular basis underpinning their development in the thymus. This work will provide vital, fundamental discoveries into how MAIT cells are produced and regulated, as we ultimately wish to harness MAIT cells to improve human health. Read moreRead less
Understanding how mitochondria divide. This project aims to investigate the molecular mechanism by which mitochondria divide. Mitochondria are the powerhouse within our cells, and they grow and divide in our cells to ensure that they are transferred to daughter cells and also so that older mitochondria can be turned over. The project plans to build on the discovery of mitochondrial membrane proteins that are involved in fission. The results of the project could provide fundamental new knowledge ....Understanding how mitochondria divide. This project aims to investigate the molecular mechanism by which mitochondria divide. Mitochondria are the powerhouse within our cells, and they grow and divide in our cells to ensure that they are transferred to daughter cells and also so that older mitochondria can be turned over. The project plans to build on the discovery of mitochondrial membrane proteins that are involved in fission. The results of the project could provide fundamental new knowledge into how the mitochondrial division machine assembles and how mitochondrial fate is determined.Read moreRead less
Aurora Kinase: Molecular, Cellular And Functional Studies Deciphering Its Role In Stroke Injury
Funder
National Health and Medical Research Council
Funding Amount
$580,993.00
Summary
In stroke patients, oxygen deprivation indirectly induces massive nerve cell death by activating an enzyme called aurora kinase A (AURKA). We aim at unravelling (i) how AURKA is activated by oxygen deprivation, (ii) where the activated AURKA is localised in cells, and (iii) how the activated AURKA induces nerve cell death.The study will benefit development of therapeutic strategies to protect against brain damage in stroke since this is novel and different target for drug targeting.
New mechanisms regulating the biogenesis of extracellular vesicles. Extracellular vesicles are small packages that contain active components derived from the cell of origin. These vesicles, released by most cell types, are critical for communication between cells. However, the processes of their formation and release remain poorly understood. This project aims to explore how ubiquitination, a type of protein modification system, controls the production of extracellular vesicles. Using a strong c ....New mechanisms regulating the biogenesis of extracellular vesicles. Extracellular vesicles are small packages that contain active components derived from the cell of origin. These vesicles, released by most cell types, are critical for communication between cells. However, the processes of their formation and release remain poorly understood. This project aims to explore how ubiquitination, a type of protein modification system, controls the production of extracellular vesicles. Using a strong collaborative team and highly innovative approaches, the project will generate new knowledge to inform how cells communicate. Expected outcomes include knowledge of broad significance to cell biology, that can be leveraged to develop extracellular vesicles as tools for various biotechnology applications in the future.Read moreRead less
Molecular mechanisms of cyclic Adenosine Monophosphate (AMP) induced apoptosis. Cyclic Adenosine Monophosphate (cAMP) is an important cellular chemical necessary for cell growth. However, de-regulated cAMP production in response to altered physiology can result in cellular death or apoptosis. This is attributed to the development of certain human diseases and this project aims to understand the molecular mechanism behind this process.
Purinergic signalling in placentation and vascular adaptation in pregnancy. Our traditional understanding of purinergic signalling in the placenta is significantly outdated and incomplete. The placenta is critical for reproduction in all eutherian mammals, delivering critical nutrition and oxygen to the developing fetus. This project aims to define the role of purinergic signalling as a critical mechanism driving placentation and angiogenesis. This is the first study of its kind and will use sop ....Purinergic signalling in placentation and vascular adaptation in pregnancy. Our traditional understanding of purinergic signalling in the placenta is significantly outdated and incomplete. The placenta is critical for reproduction in all eutherian mammals, delivering critical nutrition and oxygen to the developing fetus. This project aims to define the role of purinergic signalling as a critical mechanism driving placentation and angiogenesis. This is the first study of its kind and will use sophisticated models to improve our fundamental understanding and ability to manipulate mammalian reproduction via the purinoreceptors. This proposal builds on my skills and expertise; improving our knowledge of the processes driving placental and vascular morphogenesis and offers important discoveries for reproductive science.Read moreRead less
Only recently has it emerged that our cells have a built-in backup mechanism that instructs cells to die in extreme cases, such as when viruses have hijacked a cell. A misfiring backup mechanism is thought to underlie a number of human diseases, including inflammatory disease. Our investigation will establish a starting point for the development of novel anti-inflammatory drugs.
A New Function For An Old Enzyme: Src Protein Kinase Directs Excitotoxic Neuronal Death In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$513,975.00
Summary
In our previous investigation of how brain cells die in patients suffering from stroke, we found that stroke causes aberrant activation of an enzyme called Src in the affected brain cells. Furthermore, this aberrantly activated Src directs the brain cells to undergo cell death. Our proposal, which aims to decipher this neurotoxic mechanism of the aberrantly activated Src will benefit development of new therapeutic strategies to reduce brain damage in stroke patients.