Elucidating the mechanisms of mitochondrial DNA escape. The human body is powered by mitochondria, microscopic components of living cells that make the energy they need to function. Mitochondrial damage is linked to a wide spectrum of human diseases, from devastating syndromic illnesses to neurodegeneration and autoimmunity. This project is focused on 1) how stresses such as cancer therapy or infection cause mitochondrial damage, and 2) understanding the biological processes that are triggered i ....Elucidating the mechanisms of mitochondrial DNA escape. The human body is powered by mitochondria, microscopic components of living cells that make the energy they need to function. Mitochondrial damage is linked to a wide spectrum of human diseases, from devastating syndromic illnesses to neurodegeneration and autoimmunity. This project is focused on 1) how stresses such as cancer therapy or infection cause mitochondrial damage, and 2) understanding the biological processes that are triggered inside the cell as it tries to recover. It will give a much greater understanding of mitochondrial damage at the microscopic level, and has the potential to unlock new avenues of investigation into the causes of inflammatory and immune disorders.Read moreRead less
Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cel ....Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cell migration with relevance to the basic biology of inflammation, repair and regeneration and new innovations for cell imaging. Significant benefits are expected to arise from this new knowledge and from advanced skills training and improved national capabilities in bio-imaging and analysis.Read moreRead less
The structure of heteromeric amyloid fibrils with signaling activity. This project aims to determine the composition, structure and properties of important protein complexes involved in a newly identified cell death pathway known as necroptosis. This cell death pathway removes unwanted or damaged cells during development or infection. These necroptosis protein complexes are unusual because they have a fibrillar amyloid structure, contain more than one protein type in the fibrils and have a funct ....The structure of heteromeric amyloid fibrils with signaling activity. This project aims to determine the composition, structure and properties of important protein complexes involved in a newly identified cell death pathway known as necroptosis. This cell death pathway removes unwanted or damaged cells during development or infection. These necroptosis protein complexes are unusual because they have a fibrillar amyloid structure, contain more than one protein type in the fibrils and have a functional, signalling role. The research will determine how these fibrils form and how the structures confers biological function. It could identify features in these fibrils that can be targeted as a means of ultimately preventing tissue damage after heart attack and stroke.Read moreRead less
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.
Sugar transporters in coral symbiosis and origin of parasitism. We aim to identify how symbiotic algae feed sugar to their coral hosts. Corals need this algal sugar to exist, but no one knows how it is transferred, so understanding this crucial mechanism is hugely significant. The first benefit of this research will be a fundamental understanding about how two organisms (algae and coral) cooperate to build habitats like the Great Barrier Reef. We also aim to explore whether coral/algal coopera ....Sugar transporters in coral symbiosis and origin of parasitism. We aim to identify how symbiotic algae feed sugar to their coral hosts. Corals need this algal sugar to exist, but no one knows how it is transferred, so understanding this crucial mechanism is hugely significant. The first benefit of this research will be a fundamental understanding about how two organisms (algae and coral) cooperate to build habitats like the Great Barrier Reef. We also aim to explore whether coral/algal cooperation paved the way for the origin of parasitism. The second key outcome will be to identify the precise molecular mechanism that allowed parasitism to arise. This will benefit us through understanding the origins of important diseases such as human malaria and related infections of livestock and wildlife.
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ARC Centre of Excellence in Plant Cell Wall Biology. The ARC Centre for Plant Cell Wall Biology will define the regulatory mechanisms that control molecular, enzymic and cellular processes involved in the synthesis, deposition, re-modelling and depolymerisation of cell wall polysaccharides of cereals and grasses. Plant cell walls represent the world's largest renewable carbon resource, but the regulatory mechanisms responsible for their synthesis and assembly are not understood. Key distinguishi ....ARC Centre of Excellence in Plant Cell Wall Biology. The ARC Centre for Plant Cell Wall Biology will define the regulatory mechanisms that control molecular, enzymic and cellular processes involved in the synthesis, deposition, re-modelling and depolymerisation of cell wall polysaccharides of cereals and grasses. Plant cell walls represent the world's largest renewable carbon resource, but the regulatory mechanisms responsible for their synthesis and assembly are not understood. Key distinguishing features of the Centre will be the international, integrative, and multidisciplinary approach towards addressing major questions in plant biology, its strategy to leverage ARC funding, and its linkages with potential national and international end-users of the fundamental scientific discoveries.Read moreRead less
Investigating the dynamic nature of antibody stability. The aim of the project is to provide insights into the molecular mechanisms of antibody stability. Monoclonal antibodies have transformed the study of biological processes and represent blockbuster therapeutics for cancer and inflammation. Unfortunately, antibodies often display limited stability, which greatly hinders development. Mutations have recently been identified that render human antibodies resistant to aggregation, and high-resolu ....Investigating the dynamic nature of antibody stability. The aim of the project is to provide insights into the molecular mechanisms of antibody stability. Monoclonal antibodies have transformed the study of biological processes and represent blockbuster therapeutics for cancer and inflammation. Unfortunately, antibodies often display limited stability, which greatly hinders development. Mutations have recently been identified that render human antibodies resistant to aggregation, and high-resolution crystal structures are being used to identify function. Intriguingly, preliminary data indicates that the mutations do not affect the native antibody structure, but rather influence dynamic states. The project plans to use a combination of mutagenesis, molecular dynamics simulation and deuterium exchange to study antibody dynamics.Read moreRead less