The role of the protease inhibitor Serpinb9 in antigen cross-presentation by dendritic cells. This project will provide fundamental new insights into antigen cross-presentation, a crucial facet of the immune system's response to viral infection or neoplastic cells. It will also provide a basis for future studies into mechanisms of immune tolerance and enhance our understanding of autoimmune disease.
Investigation of a Phagocytic Synapse in the Uptake of Apoptotic Cells. Rapid clearance of cells that die by apoptosis is crucial for embryonic development, tissue turnover, and after inflammatory events. Specialised phagocytes engulf the apoptotic cell corpses in a way that minimises inflammation and prevents autoimmunity. Genetic studies have identified the key evolutionary receptors involved, but the molecular basis of this phagocytosis is still poorly understood. We have developed, and seek ....Investigation of a Phagocytic Synapse in the Uptake of Apoptotic Cells. Rapid clearance of cells that die by apoptosis is crucial for embryonic development, tissue turnover, and after inflammatory events. Specialised phagocytes engulf the apoptotic cell corpses in a way that minimises inflammation and prevents autoimmunity. Genetic studies have identified the key evolutionary receptors involved, but the molecular basis of this phagocytosis is still poorly understood. We have developed, and seek to establish, an integrated model that incorporates new findings to explain how the distinctive functions of specialised receptors can be orchestrated to achieve this function. A successful outcome to the project will provide new knowledge of value to human health.Read moreRead less
Nano-scale organisation of cellular adhesions. Cell migration is a key aspect of many normal processes but also of diseases such as cancers. This project will use a novel fluorescence microscope that can see single proteins to identify how cell adhesions are formed, remodelled and disassembled. This knowledge will help to design better drugs against cancers and novel implantable materials.
Versatile elastin based hybrid hydrogels for chondrocyte transplantation and repair. Cartilage repair is often limited after significant trauma, sports injury and disease. This project will generate a new family of hybrid biomaterials constructed by precisely blending natural and synthetic components. These novel biomaterials will establish the foundation for manufactured prefabrication and in situ injection to promote healing.
Lipid raft and cyotoskeleton organization: How membrane domains give cells direction. For a large number of cells in our body it is imperative that they are able to orientate themselves relative to their environment, sense direction and translate incoming signals. To do so it is hypothesised that lipids on the cell surface are redistributed to form specialized domains. An asymmetric distribution of membrane domains can provide cells with a front and rear end and can further concentrate and co-or ....Lipid raft and cyotoskeleton organization: How membrane domains give cells direction. For a large number of cells in our body it is imperative that they are able to orientate themselves relative to their environment, sense direction and translate incoming signals. To do so it is hypothesised that lipids on the cell surface are redistributed to form specialized domains. An asymmetric distribution of membrane domains can provide cells with a front and rear end and can further concentrate and co-ordinate signalling molecules to a specific site. The project will determine the role of lipid domain in stabilizing cell shape and their remodelling during cell migration, the digestion of foreign particles and the formation of cell-cell contacts.Read moreRead less
Heparan sulfate complexes with VEGF for control of angiogenesis in tissue engineered constructs. The national/community benefits that will arise from this work include, the generation of knowledge related to the growth of blood vessels in the presence of a synthetic polymer that has been made to look like the natural polymers present in the body. This will lead to an understanding of the underlying mechanisms involved that may have down stream effects relevant to the replacement of many types o ....Heparan sulfate complexes with VEGF for control of angiogenesis in tissue engineered constructs. The national/community benefits that will arise from this work include, the generation of knowledge related to the growth of blood vessels in the presence of a synthetic polymer that has been made to look like the natural polymers present in the body. This will lead to an understanding of the underlying mechanisms involved that may have down stream effects relevant to the replacement of many types of tissues being generated for clinical applications, including possible applications in the treatment of heart disease, the largest killer of people in the Western world. Read moreRead less
Nuclear plasticity during neutrophil migration and function. This project aims to discover how nuclear shape affects neutrophil function. Cell migration needs overall cellular plasticity and plasticity of internal structures such as the nucleus. The neutrophil, one of the most peripatetic cell types, has a specialised lobulated nucleus, thought to facilitate its mobility and function. Using zebrafish reporter lines that concurrently display the nucleus and cytoplasm, this project will display th ....Nuclear plasticity during neutrophil migration and function. This project aims to discover how nuclear shape affects neutrophil function. Cell migration needs overall cellular plasticity and plasticity of internal structures such as the nucleus. The neutrophil, one of the most peripatetic cell types, has a specialised lobulated nucleus, thought to facilitate its mobility and function. Using zebrafish reporter lines that concurrently display the nucleus and cytoplasm, this project will display the dynamic plasticity of neutrophil nuclei during neutrophil migration and function in vivo. This project seeks to use the spatiotemporal resolution of a lattice light sheet microscope to examine this further, and explore its effect on neutrophil function. The project seeks to establish morphological and mechanical principles applying not just to neutrophils, but to all migratory cell types.Read moreRead less
Biochemistry of tropoelastin: functional analysis of an essential cell-interactive domain. Elastin is ten times more durable than the best man-made synthetic rubbers because our bodies need to control life-threatening rips in skin, artery and lung. Warm-blooded animals use elastin to build diversely shaped elastic materials for multiple biological environments in these tissues. In this project, we will learn a lot more about the most preserved and functional part of elastin. These discoveries wi ....Biochemistry of tropoelastin: functional analysis of an essential cell-interactive domain. Elastin is ten times more durable than the best man-made synthetic rubbers because our bodies need to control life-threatening rips in skin, artery and lung. Warm-blooded animals use elastin to build diversely shaped elastic materials for multiple biological environments in these tissues. In this project, we will learn a lot more about the most preserved and functional part of elastin. These discoveries will increase our understanding of the grand architectural rules by which elastic protein-based structures are made. We will learn new ways to manage cell interactions in an elastic environment and define design rules to assist in the future design of new cell-binding, elastic, composite materials.Read moreRead less
Dissecting a hematopietic transcription factor complex. The development of mature active cells is a highly complex and coordinated process that is controlled largely by groups of interacting regulatory proteins. We are trying to understand, at a very detailed level, how a specific group of these proteins interact to regulate both normal blood cell development and the onset of childhood leukemias. Using this information we will try to develop reagents that can be used to inhibit these interaction ....Dissecting a hematopietic transcription factor complex. The development of mature active cells is a highly complex and coordinated process that is controlled largely by groups of interacting regulatory proteins. We are trying to understand, at a very detailed level, how a specific group of these proteins interact to regulate both normal blood cell development and the onset of childhood leukemias. Using this information we will try to develop reagents that can be used to inhibit these interactions and be used as lead compounds for treatments for disease.Read moreRead less
Cell-cell signaling in the regulation of cell polarity in plants. This project aims to investigate how plants cells communicate with each other to coordinate their growth and directionality. The project is expected to generate new knowledge in the area of plant developmental biology. Expected outcomes include a new mechanistic framework, built from the cellular level, for understanding and manipulating plant growth and the building of new international collaborations. The project should provide ....Cell-cell signaling in the regulation of cell polarity in plants. This project aims to investigate how plants cells communicate with each other to coordinate their growth and directionality. The project is expected to generate new knowledge in the area of plant developmental biology. Expected outcomes include a new mechanistic framework, built from the cellular level, for understanding and manipulating plant growth and the building of new international collaborations. The project should provide an enhanced ability to modify crop architecture to improve agricultural output.Read moreRead less