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Regulation of Stress Hormone Receptors in the Brain. Our research will provide information on how the brain controls our response to stress and will allow the development of targeted strategies to reduce the possibility during chronic stress of the development of conditions such as anxiety and depression. This will improve mental health outcomes in Australia and add to Australia's economic and social stability.
Wiring the gut's nervous system: formation and maturation of synapses. This project aims to determine how nerve circuits controlling intestinal functions develop; specifically how communication between specific nerve cells is established once they appear in the embryonic gut. It will fill a major hole in existing knowledge of mechanisms regulating the development of normal digestive behaviours.
The role of copper in the early ubiquitination pathway. This project aims to explore the role of copper in ageing and protein turnover. The removal of damaged or excess proteins is achieved by ubiquitin-tagging in all kingdoms of life. It has recently been observed that one of the earliest steps of this process appears to be driven by copper. This project aims to elaborate the precise biochemical mechanisms by which copper regulates this important tagging and protein turnover system. It proposes ....The role of copper in the early ubiquitination pathway. This project aims to explore the role of copper in ageing and protein turnover. The removal of damaged or excess proteins is achieved by ubiquitin-tagging in all kingdoms of life. It has recently been observed that one of the earliest steps of this process appears to be driven by copper. This project aims to elaborate the precise biochemical mechanisms by which copper regulates this important tagging and protein turnover system. It proposes to characterise the structure and function of a newly identified copper-dependent form of cell enzyme which could be involved in amplifying ubiquitin-tagged protein breakdown. Copper is essential for life in all domains. Identifying copper as a major regulator in protein clearance is important in understanding this fundamental biological machinery.Read moreRead less
Understanding How the Hungry Brain Regulates Metabolism. Energy homeostasis is essential for life as it ensures an adequate supply of fuel to cells of the body. This process is orchestrated by neurons in the hypothalamus of the brain. This project aims to determine the role of the extracellular matrix that surrounds hypothalamic neurons and how this regulates energy homeostasis, an area of science that is completely unexplored. This project expects to identify the composition the extracellular m ....Understanding How the Hungry Brain Regulates Metabolism. Energy homeostasis is essential for life as it ensures an adequate supply of fuel to cells of the body. This process is orchestrated by neurons in the hypothalamus of the brain. This project aims to determine the role of the extracellular matrix that surrounds hypothalamic neurons and how this regulates energy homeostasis, an area of science that is completely unexplored. This project expects to identify the composition the extracellular matrix within the hypothalamus and discover how it regulates energy homeostasis. The outcomes of this project are to provide new knowledge in understanding how the brain regulates metabolism, to promote population health & wellbeing, develop new technologies and training the next generation of researchers.Read moreRead less
Investigating the neuroprotective actions of metallo-complexes. Metal-based drugs offer an exciting new approach to treatment of neurodegeneration. However, little is known about how cells metabolise these drugs: information that is critical for further drug development. This project will determine how metal-based drugs are metabolized by neuronal cells and how this may result in therapeutic benefit.
Functional characterisation of neurons derived from embryonic stem cells and NS cells. The ability to obtain specific neurons from NS cells will revolutionise the study of nerve function, will allow the establishment of much-improved models for discovery of new drugs, and will define how enriched populations of neural cells can be obtained for applications in treatment of neurodegenerative diseases. The project will provide vital data for the emerging biotechnology industry associated will appl ....Functional characterisation of neurons derived from embryonic stem cells and NS cells. The ability to obtain specific neurons from NS cells will revolutionise the study of nerve function, will allow the establishment of much-improved models for discovery of new drugs, and will define how enriched populations of neural cells can be obtained for applications in treatment of neurodegenerative diseases. The project will provide vital data for the emerging biotechnology industry associated will applications of stem cell biology, and will stimulate clinical researchers to investigate the therapeutic potential of cell derived from NS cells.Read moreRead less
Functional studies on a novel, brain-specific, Golgi ATP-binding protein in membrane trafficking. In cells specialised for communication such as neurones, protein transport constitutes a large part of total cellular activity. A primary pathway in protein transport is trafficking from the Golgi apparatus to the cell membrane; materials destined for the cell membrane and secretion are sorted, packed and transported from the Golgi apparatus. However, the mechanisms underlying these processes at the ....Functional studies on a novel, brain-specific, Golgi ATP-binding protein in membrane trafficking. In cells specialised for communication such as neurones, protein transport constitutes a large part of total cellular activity. A primary pathway in protein transport is trafficking from the Golgi apparatus to the cell membrane; materials destined for the cell membrane and secretion are sorted, packed and transported from the Golgi apparatus. However, the mechanisms underlying these processes at the Golgi remain largely unknown. We have recently cloned a novel ATP-binding protein specifically expressed at the Golgi apparatus in human brain, and hypothesise that this protein regulates Golgi protein trafficking by interacting with two other molecules, dynamin and calcium, during cell secretion.Read moreRead less
Characterisation of a novel neural-specific ATPase in cholesterol transport. Ageing is determined by both genetic and metabolic factors. To a large part, the detailed mechanisms of ageing remain to be unexplored. Genetically, the timing of cell ageing entails the loss of telomeres (tips of chromosomes). However, the buildup of metabolic wastes resets the timing prematurely. Metabolic products accumulate from excess production or a shortfall of removal activity, which occurs in the various parts ....Characterisation of a novel neural-specific ATPase in cholesterol transport. Ageing is determined by both genetic and metabolic factors. To a large part, the detailed mechanisms of ageing remain to be unexplored. Genetically, the timing of cell ageing entails the loss of telomeres (tips of chromosomes). However, the buildup of metabolic wastes resets the timing prematurely. Metabolic products accumulate from excess production or a shortfall of removal activity, which occurs in the various parts of ageing cells in tissues such as brain. Traffic jams of cholesterol transport in the secretory pathway induce early ageing of the nerve cells. We investigate a novel mechanism controlling cholesterol transport in nerve cell ageing.Read moreRead less
The Role of Metals in the Biology of the Ageing Brain. Aims
1.To advance basic understanding of the interactions between cellular proteins and biologically important metals
2. To learn how these interactions change as the organism ages
3. To study the pathological results of aberrant metal biology using animal and cellular models of major age-dependent neurodegenerative disease.
In a rapidly ageing society, neurodegenerative disorders such as Alzheimer's and Parkinson's diseases will presen ....The Role of Metals in the Biology of the Ageing Brain. Aims
1.To advance basic understanding of the interactions between cellular proteins and biologically important metals
2. To learn how these interactions change as the organism ages
3. To study the pathological results of aberrant metal biology using animal and cellular models of major age-dependent neurodegenerative disease.
In a rapidly ageing society, neurodegenerative disorders such as Alzheimer's and Parkinson's diseases will present a medical and economic challenge demanding novel and powerful science. This research will lead both to deeper understanding of the basic mechanisms underlying such disorders and to tools for designing new and effective treatments.
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Prevention of age-related learning and memory dysfunction with novel compounds. This project will illuminate the fundamental brain changes that lead to age-related cognitive decline and to then test the validity of this as a novel therapeutic target. The expected outcome of this work will be a unique approach to the treatment of cognitive decline that will fill a significant unmet need within the community.