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
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
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.
Read moreRead less
Engineering Articular Cartilage with Zonal Structure and Function. This project addresses the National Research Priority of Promoting and Maintaining Good Health and specifically the Priority Goal of Ageing well, ageing productively. Osteoarthritis, the most common cartilage-related disease, affects nearly 1.4 million Australians, resulting in 2 in 1000 Australians undergoing total joint replacement, annually. The incidence and impact of cartilage damage on the Australian health and economy is e ....Engineering Articular Cartilage with Zonal Structure and Function. This project addresses the National Research Priority of Promoting and Maintaining Good Health and specifically the Priority Goal of Ageing well, ageing productively. Osteoarthritis, the most common cartilage-related disease, affects nearly 1.4 million Australians, resulting in 2 in 1000 Australians undergoing total joint replacement, annually. The incidence and impact of cartilage damage on the Australian health and economy is expected to increase with the ageing population. This work leads to the development of a novel cartilage engineering technology platform that addresses Frontier Technologies and will thus provide the foundation for translation of this technology to the international marketplace. Read moreRead less
Advanced optical tweezers technologies for biophysical measurements. While much is understood about the fundamental unit of life, the living cell, such as their behaviour and their biochemistry and genetics, the interface between these two is only poorly known. We will use optical tweezers, which can trap and move microscopic objects without physical contact, to measure forces on the molecular and cellular scale to study the mechanical properties of cells and biomolecules, including molecular mo ....Advanced optical tweezers technologies for biophysical measurements. While much is understood about the fundamental unit of life, the living cell, such as their behaviour and their biochemistry and genetics, the interface between these two is only poorly known. We will use optical tweezers, which can trap and move microscopic objects without physical contact, to measure forces on the molecular and cellular scale to study the mechanical properties of cells and biomolecules, including molecular motors, which are Nature's own nanomachines, advanced our knowledge of the fundamental machinery of life.Read moreRead less
Noncanonical epitope recognition by CD8+ T lymphocytes. This proposed research program will provide significant fundamental insight in the areas of immunology and vaccine design. Vaccines for many diseases remain elusive, and this project aims to improve our understanding of the precise regions within pathogens that are the targets for the killer T cells of the immune system. These regions, called epitopes, are likely to be key ingredients in many future vaccines. Although immunologists have gat ....Noncanonical epitope recognition by CD8+ T lymphocytes. This proposed research program will provide significant fundamental insight in the areas of immunology and vaccine design. Vaccines for many diseases remain elusive, and this project aims to improve our understanding of the precise regions within pathogens that are the targets for the killer T cells of the immune system. These regions, called epitopes, are likely to be key ingredients in many future vaccines. Although immunologists have gathered much information about such epitopes, recent studies have shown that some unexpected regions of pathogens are targets for killer T cells. This project will break new ground by utilising unbiased procedures to assess the relative contribution of these noncanonical epitopes to immunity.Read moreRead less
Interspecies electron transfer in biotechnology. While the project is fundamental in nature, it has direct technological gains to a wide range of biotechnology processes, and in particular, mixed culture anaerobic biotechnology. It therefore promotes Australian bioenergy, biofuel, and commodity renewable chemicals industries, and contributes to the national research priority of an Environmentally Sustainable Australia. In addition, this is a fast moving, high impact area that will demonstrate e ....Interspecies electron transfer in biotechnology. While the project is fundamental in nature, it has direct technological gains to a wide range of biotechnology processes, and in particular, mixed culture anaerobic biotechnology. It therefore promotes Australian bioenergy, biofuel, and commodity renewable chemicals industries, and contributes to the national research priority of an Environmentally Sustainable Australia. In addition, this is a fast moving, high impact area that will demonstrate excellence in Australian research on an international scale. The exciting multidisciplinary nature of the project, excellent management team, and high-class partners will also provide for an excellent experience for the three PhD candidates to be educated through the project.Read moreRead less
Molecularly engineered cell-instructive hydrogels for enhanced tissue regeneration. The outcomes of this project will be relevant to range of wounds, including burns, bed-sores, and diabetic and venous ulcers. Clearly, innovation in wound healing is urgently required as the treatment of wounds represents a significant challenge at all levels of our society, in terms of cost (physical, emotional and financial) to patients, the economy and to the wider community. Despite this obvious and overwhelm ....Molecularly engineered cell-instructive hydrogels for enhanced tissue regeneration. The outcomes of this project will be relevant to range of wounds, including burns, bed-sores, and diabetic and venous ulcers. Clearly, innovation in wound healing is urgently required as the treatment of wounds represents a significant challenge at all levels of our society, in terms of cost (physical, emotional and financial) to patients, the economy and to the wider community. Despite this obvious and overwhelming need, research in wound healing is relatively under-developed and has yet to adopt modern biotechnology and biomaterials approaches. This project is therefore directed at generating cost-effective frontier wound dressing technologies that accelerate wound repair.Read moreRead less