A microfluidic approach to study the mechanobiology of ageing blood vessels. This project aims to study the effect of the stiffening of ageing arteries in endothelial cells. It explores the changes that occur in endothelial cells using a unique microfluidic technology with tuneable wall stiffness to mimic the biophysical and biochemical properties of ageing arteries. The expected outcome is the identification of the cellular mechanisms that control endothelial responses to arterial stiffening. T ....A microfluidic approach to study the mechanobiology of ageing blood vessels. This project aims to study the effect of the stiffening of ageing arteries in endothelial cells. It explores the changes that occur in endothelial cells using a unique microfluidic technology with tuneable wall stiffness to mimic the biophysical and biochemical properties of ageing arteries. The expected outcome is the identification of the cellular mechanisms that control endothelial responses to arterial stiffening. This should provide the fundamental knowledge required to assist in the development of new therapies to tackle age-related conditions such as cardiovascular disease and dementia.Read moreRead less
Function and evolution of insect odorant receptors. This project aims to shed light on how insect odorant receptors function by using comparative genomic studies between the genetic model insect Drosophila melanogaster and a pest species, the Australian sheep blowfly. This project expects to generate knowledge of how specific chemicals activate specific receptors in order to excite sensory neurons and drive behaviour, which is not well understood. Expected outcomes include increased understandin ....Function and evolution of insect odorant receptors. This project aims to shed light on how insect odorant receptors function by using comparative genomic studies between the genetic model insect Drosophila melanogaster and a pest species, the Australian sheep blowfly. This project expects to generate knowledge of how specific chemicals activate specific receptors in order to excite sensory neurons and drive behaviour, which is not well understood. Expected outcomes include increased understanding of olfaction in insects, increased national and international collaboration, and outstanding graduate student training. This research will be of significant future benefit in deriving methods to modify the behaviour of insects of agricultural or medical importance, for example the sheep blowfly. Read moreRead less
Discovering novel allosteric probes of muscarinic acetylcholine receptors. This project aims at fostering novel approaches to selectively target vital receptors in the human body, the muscarinic acetylcholine receptors (mAChRs). By harnessing the design of receptor mutations, compounds synthesis and fluorescent imaging, the project expects to develop new pharmacological tools for a family of receptors essential for the life of all vertebrates. By enriching our understanding of this family of rec ....Discovering novel allosteric probes of muscarinic acetylcholine receptors. This project aims at fostering novel approaches to selectively target vital receptors in the human body, the muscarinic acetylcholine receptors (mAChRs). By harnessing the design of receptor mutations, compounds synthesis and fluorescent imaging, the project expects to develop new pharmacological tools for a family of receptors essential for the life of all vertebrates. By enriching our understanding of this family of receptor, the project expects to provide significant benefits to the research field by impacting on future drug discovery efforts, not only at mAChRs, but at other structurally related receptors.Read moreRead less
A novel axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Person ....A novel axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Personnel will be trained in cutting-edge techniques. The project will expand knowledge on basic immunology and cell-cell cooperation. It will generate intellectual property for the biotechnology sector to develop new commercial products that might improve the health of humans and also animals of economic importance.Read moreRead less
Mechanisms of itch - from endosomal signalling to neural circuits. This project aims to investigate the cellular and circuit mechanisms of itch transmission in the spinal cord by defining the activation and propagation of itch-specific signals. This project expects to generate new knowledge in the area of neuronal signalling and circuitry using novel electrophysiological approaches that target and manipulate specific nerves and cellular components. The project will characterise signalling within ....Mechanisms of itch - from endosomal signalling to neural circuits. This project aims to investigate the cellular and circuit mechanisms of itch transmission in the spinal cord by defining the activation and propagation of itch-specific signals. This project expects to generate new knowledge in the area of neuronal signalling and circuitry using novel electrophysiological approaches that target and manipulate specific nerves and cellular components. The project will characterise signalling within specific spinal subcircuits in order to understand the mechanisms of receptor activation and signalling, and investigate how circuit activity is regulated. This project expects to advance fundamental understanding of itch signalling in the nervous system and provide avenues for future therapeutics.Read moreRead less
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.
Read moreRead less
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
The Role of Lck/CD8 Association in Negatively Regulating T cell Activation. This proposal aims to advance our fundamental understanding of how T cell recognition of antigens translates into a T cell activating signal. The proposal will establish whether the major T cell coreceptor also acts as a negative regulator of T cell activation in vivo when antigen recognition is unorthodox. It will also determine whether certain subsets of T cells naturally lack coreceptors in order to facilitate unortho ....The Role of Lck/CD8 Association in Negatively Regulating T cell Activation. This proposal aims to advance our fundamental understanding of how T cell recognition of antigens translates into a T cell activating signal. The proposal will establish whether the major T cell coreceptor also acts as a negative regulator of T cell activation in vivo when antigen recognition is unorthodox. It will also determine whether certain subsets of T cells naturally lack coreceptors in order to facilitate unorthodox antigen recognition. Thus, the proposal will significantly advance our understanding of, and establish new paradigms around, the regulation of T cell activation. Expected long term benefits outside the scope of this proposal include improved immunotherapies and vaccines designed to elicit or suppress T cell responses.Read moreRead less
Elucidating the determinants of cation import across the kingdoms of life. The metal ion manganese is essential to all forms of life. This project aims to investigate how this poorly abundant cation is selectively acquired from the chemical complexity of the environment for import into cells by using state-of-the-art biochemical and microbiological techniques. This project expects to define the fundamental basis for how bacterial, archaeal and eukaryotic plastid cation-selective importers can di ....Elucidating the determinants of cation import across the kingdoms of life. The metal ion manganese is essential to all forms of life. This project aims to investigate how this poorly abundant cation is selectively acquired from the chemical complexity of the environment for import into cells by using state-of-the-art biochemical and microbiological techniques. This project expects to define the fundamental basis for how bacterial, archaeal and eukaryotic plastid cation-selective importers can discriminate manganese from chemical similar cations to achieve selective uptake. The expected outcomes of this work will be an understanding of the fundamental basis for selective metal import in biological systems. This should provide benefits for industry through synthetic biological applications of this knowledge. Read moreRead less
How do cytokine receptors transmit signals? This project aims to determine the mechanisms of signal transmission by cytokine receptors using state-of-the-art microscopy techniques. Cytokines are small proteins that act as messengers between cells and play fundamental roles in biology. Cytokines bind to receptors on the surface of cells, producing a response within the cells. Yet, how the message is transmitted across the cell membrane is not well understood. Expected outcomes of this project inc ....How do cytokine receptors transmit signals? This project aims to determine the mechanisms of signal transmission by cytokine receptors using state-of-the-art microscopy techniques. Cytokines are small proteins that act as messengers between cells and play fundamental roles in biology. Cytokines bind to receptors on the surface of cells, producing a response within the cells. Yet, how the message is transmitted across the cell membrane is not well understood. Expected outcomes of this project include discovery of mechanisms general to cytokine signalling and new approaches to investigate cytokine biology. This new knowledge will benefit efforts to understand and modulate cytokine signalling in animals and humans, with future impacts in the agriculture, veterinary, and health sectors.Read moreRead less