Movement of mitochondria between cells. This project aims to characterise how mitochondria move between cells into grafted cells with dysfunctional mitochondrial function. How mitochondria reach the acceptor cell and how they move from the donor cell is not known. The project will use a 'bottom-up' approach, starting from a reconstituted system, via in vitro, co-culture stage to a relevant biological model, increasing complexity and biological relevance. It will document that the process of mito ....Movement of mitochondria between cells. This project aims to characterise how mitochondria move between cells into grafted cells with dysfunctional mitochondrial function. How mitochondria reach the acceptor cell and how they move from the donor cell is not known. The project will use a 'bottom-up' approach, starting from a reconstituted system, via in vitro, co-culture stage to a relevant biological model, increasing complexity and biological relevance. It will document that the process of mitochondrial intercellular movement is dependent on intercellular bridges and a specific mobility system. The project is of high relevance for cell biology.Read moreRead less
Mixing the jigsaw pieces of natural products: new molecules-new properties. This project aims to examine the capacity of exploiting the bacterial biosynthetic machinery to fast-track access to analogues of natural products. Due to increased drug resistance, new reservoirs of natural products are needed for evaluation as future drugs. Desferrioxamine B will be used as a model natural product to establish the biosynthesis of new analogues in bacterial culture supplemented with unsaturated, fluorin ....Mixing the jigsaw pieces of natural products: new molecules-new properties. This project aims to examine the capacity of exploiting the bacterial biosynthetic machinery to fast-track access to analogues of natural products. Due to increased drug resistance, new reservoirs of natural products are needed for evaluation as future drugs. Desferrioxamine B will be used as a model natural product to establish the biosynthesis of new analogues in bacterial culture supplemented with unsaturated, fluorinated or deuterated building blocks. The intended outcomes are to deliver advances in methods for generating structurally diverse pools of natural products, new label-free probes, knowledge of natural product biosynthesis, and excellence in training research students in frontier methods in chemical biology and drug discovery.Read moreRead less
Control of actin assembly by cell-cell adhesion: molecular effectors and higher order function. Functional cooperation between the actin cytoskeleton and cadherin cell-cell adhesion molecules plays critical roles during development and morphogenesis. This proposal builds on my lab's recent discovery that E-cadherin interacts with and regulates the Arp2/3 actin nucleator complex, a central determinant of actin assembly in cells. We will explore key implications of this finding, concentrating on d ....Control of actin assembly by cell-cell adhesion: molecular effectors and higher order function. Functional cooperation between the actin cytoskeleton and cadherin cell-cell adhesion molecules plays critical roles during development and morphogenesis. This proposal builds on my lab's recent discovery that E-cadherin interacts with and regulates the Arp2/3 actin nucleator complex, a central determinant of actin assembly in cells. We will explore key implications of this finding, concentrating on defining the molecular mechanisms that regulate Arp2/3 and actin assembly in cadherin-based adhesion. Our work combines molecular characterization of regulatory mechanisms and proteomic searches for new regulators, with tests of the higher-order function of this novel process in cell adhesion and recognition.Read moreRead less
Balancing cadherin-actin cooperation: the key regulatory role of Ena/VASP proteins. This project analyses a fundamental mechanism of how cells work together in tissues. Understanding the fundamental mechanisms of how cells work will provide important basic scientific information to enrich the scientific expertise in Australia and its part in the international community, generate insights relevant for understanding human disease and physical degeneration, and support the training of young scienti ....Balancing cadherin-actin cooperation: the key regulatory role of Ena/VASP proteins. This project analyses a fundamental mechanism of how cells work together in tissues. Understanding the fundamental mechanisms of how cells work will provide important basic scientific information to enrich the scientific expertise in Australia and its part in the international community, generate insights relevant for understanding human disease and physical degeneration, and support the training of young scientists in Australia.Read moreRead less
New antibiotics: engaging microbial chemical diversity. This project will explore Australian microbial biodiversity, to detect, isolate and identify new natural chemicals with potent and selective antibacterial properties. Knowledge of these molecules will inspire and inform the development of new classes of antibiotic, effective against multi-drug resistant infections.
Tissue tension homeostasis by junctional mechanosensing. This project examines how tissues use mechanical tension to preserve their integrity. This comes from the recent appreciation that cells pull on the connections between each other to generate tension. Further, molecular mechanisms exist for cells to sense changes in this tension and then to enlist the appropriate responses to restore tension. The project aims to test how local changes in tension are detected and corrected, when tissue inte ....Tissue tension homeostasis by junctional mechanosensing. This project examines how tissues use mechanical tension to preserve their integrity. This comes from the recent appreciation that cells pull on the connections between each other to generate tension. Further, molecular mechanisms exist for cells to sense changes in this tension and then to enlist the appropriate responses to restore tension. The project aims to test how local changes in tension are detected and corrected, when tissue integrity is compromised by very different causes. The project endeavours to establish a new conceptual paradigm for understanding tissue homeostasis, based on cell biology and biomechanics, with implications for developmental biology and tissue engineering.Read moreRead less
Understanding the molecular mechanisms regulating neuronal fusion. Neurons are tightly connected individual cells that communicate through chemical and electrical signals, and this project aims to discover the key molecules that allow these cells to remain as individual units without fusing with each other. The nervous system, unlike other tissues, is made of discrete individual cells, connected by chemical and electrical synapses but not by cytoplasmic continuity. However, how this is achieved ....Understanding the molecular mechanisms regulating neuronal fusion. Neurons are tightly connected individual cells that communicate through chemical and electrical signals, and this project aims to discover the key molecules that allow these cells to remain as individual units without fusing with each other. The nervous system, unlike other tissues, is made of discrete individual cells, connected by chemical and electrical synapses but not by cytoplasmic continuity. However, how this is achieved and how neurons maintain their individuality during development, remodelling and ageing is unknown. The project aims to address this gap using a genetic approach and the nematode Caenorhabditis elegans as an experimental system. The results may provide insights into how the nervous system develops and functions.Read moreRead less
Developing a multicomponent platform for targeted gene delivery. Gene delivery systems are important tools in biological research and offer many exciting future prospects. Delivering gene material is very difficult in practice: rapid deterioration, poor cell uptake, and reaching the right tissue and cell types are major obstacles. Ways to overcome each barrier individually have been suggested in existing research but these components have not yet been combined in a single solution, which this pr ....Developing a multicomponent platform for targeted gene delivery. Gene delivery systems are important tools in biological research and offer many exciting future prospects. Delivering gene material is very difficult in practice: rapid deterioration, poor cell uptake, and reaching the right tissue and cell types are major obstacles. Ways to overcome each barrier individually have been suggested in existing research but these components have not yet been combined in a single solution, which this project will tackle. This proposal aims to create a technology to stabilise and deliver active gene material to target cells. The gene delivery tool developed in this project will advance biological research greatly with many potential future applications.Read moreRead less
Chemical probes to dissect the cell cycle of globally important parasites . This project aims to develop new reagents, called chemical probes, to visualise key biological events in globally important pathogens. We will use innovative chemistry to modify the building blocks of DNA and provide researchers with essential tools to 'see' DNA synthesis in order to study growth and replication of pathogens in combination with microscopy. This project expects to support a major technical advance that wi ....Chemical probes to dissect the cell cycle of globally important parasites . This project aims to develop new reagents, called chemical probes, to visualise key biological events in globally important pathogens. We will use innovative chemistry to modify the building blocks of DNA and provide researchers with essential tools to 'see' DNA synthesis in order to study growth and replication of pathogens in combination with microscopy. This project expects to support a major technical advance that will address important gaps in our understanding of many pathogens (e.g. those that cause malaria and tuberculosis), at both the cellular and molecular levels. This should provide significant benefits by enabling researchers worldwide to identify new intervention opportunities that target unique aspects of pathogen biology.Read moreRead less
CX3C chemokine signalling in the olfactory epithelium and its role in the self regeneration of the olfactory system. The current proposal will explore new venues in adult neural stem cell research and contribute to the further development of molecular biology and neuroscience research in Western Australia and Australia. The use of neural stem cells holds therapeutic promise for the treatment of a wide variety of neurological conditions, including neurotrauma and stroke. The proposed research wil ....CX3C chemokine signalling in the olfactory epithelium and its role in the self regeneration of the olfactory system. The current proposal will explore new venues in adult neural stem cell research and contribute to the further development of molecular biology and neuroscience research in Western Australia and Australia. The use of neural stem cells holds therapeutic promise for the treatment of a wide variety of neurological conditions, including neurotrauma and stroke. The proposed research will provide new data on the fundamental cellular and molecular events that are required to trigger the birth, differentiation and conditions for growth of new neurons in the adult nervous system. The generation of such insights will be critical for any translational research.
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