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
The bHLH.PAS transcription factors: Determinants of dimerization specificity and high affinity DNA binding. This program of fundamental research will advance our knowledge of the way essential proteins act to correctly regulate critical biological processes. A detailed understanding of these processes at the molecular level has the potential to contribute to the design of pharmaceutical compounds to assist in the treatment of diseases such as ischaemia, myocardial infarction and tumour progress ....The bHLH.PAS transcription factors: Determinants of dimerization specificity and high affinity DNA binding. This program of fundamental research will advance our knowledge of the way essential proteins act to correctly regulate critical biological processes. A detailed understanding of these processes at the molecular level has the potential to contribute to the design of pharmaceutical compounds to assist in the treatment of diseases such as ischaemia, myocardial infarction and tumour progression. The work will contribute to the training of one or more graduate students in a technologically advancing and internationally competitive field.Read moreRead less
New mechanisms regulating the biogenesis of extracellular vesicles. Extracellular vesicles are small packages that contain active components derived from the cell of origin. These vesicles, released by most cell types, are critical for communication between cells. However, the processes of their formation and release remain poorly understood. This project aims to explore how ubiquitination, a type of protein modification system, controls the production of extracellular vesicles. Using a strong c ....New mechanisms regulating the biogenesis of extracellular vesicles. Extracellular vesicles are small packages that contain active components derived from the cell of origin. These vesicles, released by most cell types, are critical for communication between cells. However, the processes of their formation and release remain poorly understood. This project aims to explore how ubiquitination, a type of protein modification system, controls the production of extracellular vesicles. Using a strong collaborative team and highly innovative approaches, the project will generate new knowledge to inform how cells communicate. Expected outcomes include knowledge of broad significance to cell biology, that can be leveraged to develop extracellular vesicles as tools for various biotechnology applications in the future.Read moreRead less
Development of novel therapies for the treatment of cancer. Both aging and obesity are significant risk factors for cancer and are becoming a burden on the health care budget. The proposed novel cancer therapy will improve current cancer treatments by enhancing their efficacy, thereby reducing the required dose and minimizing side effects. Such an outcome would not only benefit the well being of the individual but would achieve significant health care cost savings.
Investigation of the fundamental roles of class Ib MHC (major histocompatibility complex) molecules in immunity. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide insight into the roles of a poorly understood class of immune molecules. This will improve our understanding of the regulation of immunity, and the knowledge gained will increase Australia's international research profile.
Small heat-shock molecular chaperone proteins and amyloid fibrils. This proposal addresses the fundamental mechanisms of protein aggregation associated with debilitating age-related diseases, e.g. Alzheimer's, Parkinson's and cataract, and the prevention of aggregation via the action of a group of molecular chaperone proteins known as small heat-shock proteins. With the ageing population, the prevalence of these diseases will increase significantly over the next 20 years. Understanding and treat ....Small heat-shock molecular chaperone proteins and amyloid fibrils. This proposal addresses the fundamental mechanisms of protein aggregation associated with debilitating age-related diseases, e.g. Alzheimer's, Parkinson's and cataract, and the prevention of aggregation via the action of a group of molecular chaperone proteins known as small heat-shock proteins. With the ageing population, the prevalence of these diseases will increase significantly over the next 20 years. Understanding and treating these diseases will therefore have significant long-term health benefits. Furthermore, the highly structured protein aggregates that form as hallmarks of many of these diseases have potential wide ranging applications in the emerging field of bionanotechnology, e.g. as nanowires and biofilms.Read moreRead less
Use of mitochondrial electron transport chain mutants to evaluate how non-phosphorylating respiration influences plant metabolite profiles and stress tolerance. This project uses transgenic plant technology to elucidate how mitochondrial function impacts on the profile of metabolites in plant cell and tissues and whether altering these profiles influences a plant's ability tog row in harsh conditions. It will contribute to our fundamental knowledge of plant metabolism using a metabolomic anaylsi ....Use of mitochondrial electron transport chain mutants to evaluate how non-phosphorylating respiration influences plant metabolite profiles and stress tolerance. This project uses transgenic plant technology to elucidate how mitochondrial function impacts on the profile of metabolites in plant cell and tissues and whether altering these profiles influences a plant's ability tog row in harsh conditions. It will contribute to our fundamental knowledge of plant metabolism using a metabolomic anaylsis of plant stress response. This will be achieved using new high-throughput technologies, allowing reliable qualitative and quantitative analysis of large numbers of samples. This approach will compliment existing genomic and proteomic analyses of plants exposed to abiotic stress.Read moreRead less
Interactions of Insulin-like Growth Factors and their Binding Proteins with Vitronectin: a structural basis for antagonist design and development. Tissue Therapies Ltd has shown that a patented combination of three biosynthetic molecules, VitroGroR, can promote tissue repair effectively. This project will use biophysical and biochemical techniques to investigate precisely how these molecules interact, and hence provide a rational basis for future developments and improvements of this exciting n ....Interactions of Insulin-like Growth Factors and their Binding Proteins with Vitronectin: a structural basis for antagonist design and development. Tissue Therapies Ltd has shown that a patented combination of three biosynthetic molecules, VitroGroR, can promote tissue repair effectively. This project will use biophysical and biochemical techniques to investigate precisely how these molecules interact, and hence provide a rational basis for future developments and improvements of this exciting new therapeutic strategy.
Conversely, this information would also facilitate the development of antagonists to VitroGroR complexes would provide novel opportunities to treat diseases such as cancer and atherosclerosis that involve excessive production of its component molecules.Read moreRead less
Determining the regulation of vitamin D metabolism. The proposed project will lead to a better understanding of factors that influence the biological function of vitamin D. This will impact in several areas of human health and will provide new avenues for the development of preventative approaches and treatment of cancer. This project is based on the use of 'Frontier Technologies' that will be applied to elucidate basic biological questions.
Structural studies of the interactions of actinin-4 and intracellular signalling proteins. The intracellular signalling cascade plays important roles in cellular processes such as growth and differentiation by exerting changes in gene expression or remodelling of the intracellular protein framework. The actin-based cytoskeleton is one such network of proteins responsible for a number of processes including cell division, migration and adhesion to other cells and tissues. This proposal aims to un ....Structural studies of the interactions of actinin-4 and intracellular signalling proteins. The intracellular signalling cascade plays important roles in cellular processes such as growth and differentiation by exerting changes in gene expression or remodelling of the intracellular protein framework. The actin-based cytoskeleton is one such network of proteins responsible for a number of processes including cell division, migration and adhesion to other cells and tissues. This proposal aims to understand how actinin-4, a component of the actin cytoskeleton in non-muscle tissues, interacts with and is stimulated by proteins of the intracellular signalling cascade.Read moreRead less