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The colour of cellular aging: a deep probe of cellular processes. Understanding why we age and whether aging is preventable are profound research challenges, which must be first tackled at a cellular level. Building on our advances in non-invasive colour monitoring of cell function, this project aims to uncover intimate links between cellular processes and aging in cells that must survive for many decades such as oocytes and neurons. We will explore the tantalising possibility to rejuvenate such ....The colour of cellular aging: a deep probe of cellular processes. Understanding why we age and whether aging is preventable are profound research challenges, which must be first tackled at a cellular level. Building on our advances in non-invasive colour monitoring of cell function, this project aims to uncover intimate links between cellular processes and aging in cells that must survive for many decades such as oocytes and neurons. We will explore the tantalising possibility to rejuvenate such aged cells by interfering with molecular master switches of aging. A unique machine learning approach will be applied for finding the most effective interventions. The results will have broad impact beyond the science of aging, in the areas of female fertility, neurodegeneration and immunity.
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Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor ....Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor of copper sensitivity proteins, that contribute to this key virulence trait. The expected outcomes will be fundamental new knowledge of metallo-protein diversity, bacterial virulence mechanisms, and membrane protein function with potential impact on health, environment, and biotechnology.Read moreRead less
Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our ....Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our new multi-layered systems biology strategy to elucidate the first comprehensive understanding of the cell biology that underlies cell state changes. These studies are a major step toward understanding the fundamentals of life. Read moreRead less
Elucidating the roles of steroid receptors in mitochondria. This project aims to elucidate the roles of newly discovered steroid receptors in the functions of mitochondria. The project will characterise their impact on cellular respiration, oxidative stress, and the induction of inflammation. By defining these processes in the healthy state and in response to common environmental challenges of infection and smoke exposure, the project will characterise the fundamental biology of entirely new pro ....Elucidating the roles of steroid receptors in mitochondria. This project aims to elucidate the roles of newly discovered steroid receptors in the functions of mitochondria. The project will characterise their impact on cellular respiration, oxidative stress, and the induction of inflammation. By defining these processes in the healthy state and in response to common environmental challenges of infection and smoke exposure, the project will characterise the fundamental biology of entirely new processes of how normal body hormones and administered steroids may function. This may eventually lead to new and more effective ways to control inflammation that will have significant benefits to mammalian health and improve health care and agriculture outcomes.Read moreRead less
How the red blood cell loses its nucleus. This project aims to provide insights into erythroid enucleation, the process by which red blood cells extrude their nucleus so that they can circulate through the microvasculature. Although the enucleated character of mammalian red blood cells has been known for more than 150 years, the mechanism underlying this process is virtually unknown. This project will use a live imaging approach to characterise in vivo the cellular interactions and molecular pat ....How the red blood cell loses its nucleus. This project aims to provide insights into erythroid enucleation, the process by which red blood cells extrude their nucleus so that they can circulate through the microvasculature. Although the enucleated character of mammalian red blood cells has been known for more than 150 years, the mechanism underlying this process is virtually unknown. This project will use a live imaging approach to characterise in vivo the cellular interactions and molecular pathways required for enucleation. The project will provide a molecular and cellular road map of enucleation that may be utilised to enhance the bulk therapeutic in vitro production of red blood cells for veterinary and human purposes.Read moreRead less
Molecular mechanisms of signalling by plant immune receptors. This project aims to understand how resistance proteins function and to find new sources of these proteins. Plant diseases account for 15% loss of global crop production, representing a threat to food security. Fungicides, one key form of protection, represent environmental concerns. The other key form of protection corresponds to resistance gene breeding, which is limited by lengthy breeding processes, restricted choice of genes from ....Molecular mechanisms of signalling by plant immune receptors. This project aims to understand how resistance proteins function and to find new sources of these proteins. Plant diseases account for 15% loss of global crop production, representing a threat to food security. Fungicides, one key form of protection, represent environmental concerns. The other key form of protection corresponds to resistance gene breeding, which is limited by lengthy breeding processes, restricted choice of genes from sexually compatible species and short effective time spans in the field. Building on previous research, this project aims to characterise the molecular basis of the Toll/interleukin-1 receptor domain-mediated nicotinamide adenine dinucleotide (NAD+) cleavage and the structural architecture of plant NLR complexes. This knowledge will support the long-term objective of protecting crops from pathogens.Read moreRead less
Unravelling the mechanisms of sodium-selectivity in biological ion channels. The aim of this project is to determine the origins of protein-mediated sodium ion transport across cell membranes. The project expects to reveal the mechanisms of selective ion conduction in different sodium-selective ion channels using advanced computer simulations, in concert with non-canonical mutation experiments that target the roles of protein chemistry. The expected outcome is improved understanding of how prote ....Unravelling the mechanisms of sodium-selectivity in biological ion channels. The aim of this project is to determine the origins of protein-mediated sodium ion transport across cell membranes. The project expects to reveal the mechanisms of selective ion conduction in different sodium-selective ion channels using advanced computer simulations, in concert with non-canonical mutation experiments that target the roles of protein chemistry. The expected outcome is improved understanding of how proteins discriminate between ion species, challenging theories that have stood for decades. The results should provide benefits in the form of basic understanding relevant to ion transport phenomena in biology and novel materials, with atomic-level views of nervous system function to guide future directions in drug development.
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Undermining fungal defences by targeting their functional amyloid armour. This project will determine how a protective protein coating forms on the surface of fungal spores and infectious structures. This coating is comprised of amyloid protein fibrils and is used by fungi to improve efficiency of infection and to avoid detection by the host plant or animal. We have discovered novel small molecules that prevent the fibrils from forming. This project will use these molecules to reveal the details ....Undermining fungal defences by targeting their functional amyloid armour. This project will determine how a protective protein coating forms on the surface of fungal spores and infectious structures. This coating is comprised of amyloid protein fibrils and is used by fungi to improve efficiency of infection and to avoid detection by the host plant or animal. We have discovered novel small molecules that prevent the fibrils from forming. This project will use these molecules to reveal the details of the fibril assembly mechanism and find the best way to undermine this fungal defence system. This knowledge will enable the development of potent small molecule inhibitors to treat fungal infections that blight crops and harm animals, and the production of new layered biomaterials for nanotechnology applications.Read moreRead less
The effect of methylation and phosphorylation on ribosome function. This project aims to discover how cells regulate ribosome function and selectivity, by modifying their ribosomal proteins. This affects protein synthesis, a process which is central to the growth of all living things. Expected outcomes include new knowledge on the regulation of protein synthesis, improved techniques for the study of this process and an enhanced capacity for international collaboration. New avenues for the artifi ....The effect of methylation and phosphorylation on ribosome function. This project aims to discover how cells regulate ribosome function and selectivity, by modifying their ribosomal proteins. This affects protein synthesis, a process which is central to the growth of all living things. Expected outcomes include new knowledge on the regulation of protein synthesis, improved techniques for the study of this process and an enhanced capacity for international collaboration. New avenues for the artificial regulation of the ribosome may also emerge, relevant to synthetic biology and the engineering of industrial yeasts. The project should provide significant new findings for the research community, generate research citations and contribute to a highly skilled workforce by the training of staff and students.Read moreRead less
Determining how the soluble dietary fibre beta-glucan is made in cereals. This Project aims to define the molecular mechanisms that control the processes involved in the biosynthesis and regulation of mixed linkage glucan, a major soluble dietary fibre in the cell walls of cereal grains. Plant cell walls determine the quality of most plant-based products used in modern human societies, yet the regulatory mechanisms responsible for their modulation are not well understood. Key distinguishing feat ....Determining how the soluble dietary fibre beta-glucan is made in cereals. This Project aims to define the molecular mechanisms that control the processes involved in the biosynthesis and regulation of mixed linkage glucan, a major soluble dietary fibre in the cell walls of cereal grains. Plant cell walls determine the quality of most plant-based products used in modern human societies, yet the regulatory mechanisms responsible for their modulation are not well understood. Key distinguishing features of the Project will be the international, integrative, and multidisciplinary approach towards addressing this major challenge in plant biology and the potential of the fundamental scientific discoveries to benefit end-users in the food, feed and beverage industries.Read moreRead less