The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and ....The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and damaged proteins. This work is important because some diseases (eg, Alzheimers disease) involve the toxic effects of abnormal protein precipitation. Understanding how clusterin works may help in developing better treatments for these diseases.Read moreRead less
Androgen receptor: A master regulator of lipid metabolism. This project aims to understand how male sex hormones, or androgens, affect the amount and metabolism of fats in normal body tissues. By integrating our multi-disciplinary expertise in androgen action, molecular biology, metabolism and bioinformatics with novel techniques and instrumentation, this collaboration expects to generate the first detailed picture of how fat metabolism is controlled by androgens in humans, and how closely this ....Androgen receptor: A master regulator of lipid metabolism. This project aims to understand how male sex hormones, or androgens, affect the amount and metabolism of fats in normal body tissues. By integrating our multi-disciplinary expertise in androgen action, molecular biology, metabolism and bioinformatics with novel techniques and instrumentation, this collaboration expects to generate the first detailed picture of how fat metabolism is controlled by androgens in humans, and how closely this relates to mice. Expected outcomes and benefits will be a new understanding of which aspects of fat metabolism are most influenced by androgens, and an ability to anticipate potential metabolic impacts of natural or pharmacological fluctuations in androgen levels in humans, laboratory animals and livestock.Read moreRead less
Rejuvenating adult stem cells. This project aims to uncover intimate links between metabolic regulation and longevity in adult stem cells, the source of all cells in the body. Understanding why we age and whether ageing is preventable are research challenges which must be first attacked at a cellular level. This project will try to rejuvenate aged stem cells by interfering with a prospective molecular master switch of aging and also develop an approach to identify and select youthful stem cells. ....Rejuvenating adult stem cells. This project aims to uncover intimate links between metabolic regulation and longevity in adult stem cells, the source of all cells in the body. Understanding why we age and whether ageing is preventable are research challenges which must be first attacked at a cellular level. This project will try to rejuvenate aged stem cells by interfering with a prospective molecular master switch of aging and also develop an approach to identify and select youthful stem cells. The results are expected to be important beyond informing the science of ageing, in the areas of tissue engineering, wound healing, embryology and cancer.Read moreRead less
How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.Read moreRead less
Defining the spatial and temporal regulation of neurite branching. This project aims to identify mechanisms via which the cytoskeleton regulates the branching of nerve cell extensions. The formation of branched cell extensions is essential for establishing a complex network of connecting and communicating nerve cells in all higher organisms. This project expects that by combining advanced light microscopy technology and recently developed tools for the study of the cell architecture in vitro and ....Defining the spatial and temporal regulation of neurite branching. This project aims to identify mechanisms via which the cytoskeleton regulates the branching of nerve cell extensions. The formation of branched cell extensions is essential for establishing a complex network of connecting and communicating nerve cells in all higher organisms. This project expects that by combining advanced light microscopy technology and recently developed tools for the study of the cell architecture in vitro and in vivo, we will be able to define the molecular changes in neurites that control neurite branching. This should provide significant benefits, such as gaining crucial insights into the mechanisms of forming complex neuronal networks.Read moreRead less
Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innov ....Mechanisms of memory function involving site-specific tau phosphorylation. This project aims to understand the molecular principles that facilitate encoding, maintenance and retrieval of memories in the brain. To store memories in brain circuits, electrical and chemical signals are crucial. Brain cells can integrate signals into biochemical modifications of intracellular proteins. The nature of the protein modifications that represent memory within brain cells is unknown. This project uses innovative genome editing, mathematical modelling and proteomic approaches, to study how biochemical modifications of a key protein called tau help encode and retrieve memories. These molecular insights will make a significant advance in the current understanding of a brain function that is essential to all human activities.Read moreRead less
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
Discovery and directed evolution of small molecule biosensors. This project aims to address the need for novel small molecule biosensing capability in diverse fields including food and wine production, environmental monitoring, biocatalysis, and diagnostics using a synthetic biology approach. The significance of this work is the development of new biosensors by a strong interdisciplinary team contributing bioinformatics to identify new biosensors, innovative protein engineering approaches, and c ....Discovery and directed evolution of small molecule biosensors. This project aims to address the need for novel small molecule biosensing capability in diverse fields including food and wine production, environmental monitoring, biocatalysis, and diagnostics using a synthetic biology approach. The significance of this work is the development of new biosensors by a strong interdisciplinary team contributing bioinformatics to identify new biosensors, innovative protein engineering approaches, and cutting-edge directed evolution methodologies. Intended outcomes include enhanced institutional capacity for interdisciplinary collaboration; discovery of fundamentally important bacterial sensors; and development of synthetic regulatory circuits enabling outgrowth of non-biological biocatalysis industries.Read moreRead less
The fate of dietary selenium in vivo; a direct approach to linking chemical form with biological activity. Dietary selenium supplementation has great potential as a preventative treatment for a range of human health conditions, including cancer, that widely affect the Australian population. However, the adverse effects of such treatments are not fully recognised. This project will increase our knowledge of how selenium compounds are stored and utilised in the body and relate the information to c ....The fate of dietary selenium in vivo; a direct approach to linking chemical form with biological activity. Dietary selenium supplementation has great potential as a preventative treatment for a range of human health conditions, including cancer, that widely affect the Australian population. However, the adverse effects of such treatments are not fully recognised. This project will increase our knowledge of how selenium compounds are stored and utilised in the body and relate the information to clinical observations regarding dietary intake of selenium and other compounds. The new understanding generated will delineate the conditions for safe intake, so that the beneficial effects associated with selenium supplementation may be harnessed more effectively.Read moreRead less
Development of Pyrrolopyrimidines as Inhibitors of ATP-Binding Proteins. This project seeks to generate analogues of natural products that have been found to be active against cancer cells and tropical parasites. The new materials produced by this project will aid in the study of biochemical processes involved in diseases such as cancer and lymphatic filariasis, thus leading the way to development of these compounds as potential treatments for such diseases.