Structural and Functional Aspects of the Allosteric Regulation of Pyruvate Carboxylase by Acyl-CoA Compounds. Pyruvate carboxylase occupies a central location in intermediary metabolism catalysing the formation of oxaloacetate, a key component of the Krebs' tricarboxylic acid cycle especially in its synthetic modes in gluconeogenesis, lipogenesis and in the synthesis of neurotransmitters.
This project aims: (i) To produce crystals of pyruvate carboxylase for determining its structure by X-ra ....Structural and Functional Aspects of the Allosteric Regulation of Pyruvate Carboxylase by Acyl-CoA Compounds. Pyruvate carboxylase occupies a central location in intermediary metabolism catalysing the formation of oxaloacetate, a key component of the Krebs' tricarboxylic acid cycle especially in its synthetic modes in gluconeogenesis, lipogenesis and in the synthesis of neurotransmitters.
This project aims: (i) To produce crystals of pyruvate carboxylase for determining its structure by X-ray diffraction; (ii) To use affinity-labelling to determine the amino acid residues in the binding site of the enzyme's allosteric activator, acetyl-CoA; (iii) To construct chimeric enzymes from different species to define regions of the enzyme which affect its responses to its important allosteric activator, acetyl-CoA.
Read moreRead less
The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu pr ....The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu proteins of two proteins in the BMP pathway. Verification of a post-transcriptional regulatory mechanism for cell fate determination would be a major discovery, and may prompt investigation of how to harness the neuron-inducing function of the Hu proteins to address the therapeutic need for new neurons in neurologic diseases.Read moreRead less
Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests tha ....Truncating presenilin mutations and their effects on gamma-secretase activity, tau and beta-catenin - insights into Alzheimers disease and cancer. Cancer and dementia are primarily afflictions of the aged and are increasingly important in an aging Australian population. 95% of all Alzheimer's disease is spontaneous (not inherited) but we know little about the molecular mechanisms underlying it. Our discovery that truncated presenilin proteins potently inhibit normal protein function suggests that changes in presenilin function in aged cells might be a common molecular link between spontaneous and inherited Alzheimer's disease and could contribute to frontotemporal dementia and cancer. Our research will show whether this phenomenon might provide a breakthrough in our understanding of these diseases and be a productive area for research into their amelioration and/or prevention.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0347607
Funder
Australian Research Council
Funding Amount
$306,000.00
Summary
FishWorks - collaborative infrastructure for zebrafish research. Zebrafish have emerged as a powerful and cost-effective animal model for studying development, biology, and disease. FishWorks represents a large-scale co-operative initiative to develop state-of-the-art zebrafish housing, manipulation, genomics and screening infrastructure in Australia. This will both support and further enhance a core group of high quality researchers to engage in cutting-edge research in areas of acknowledged ex ....FishWorks - collaborative infrastructure for zebrafish research. Zebrafish have emerged as a powerful and cost-effective animal model for studying development, biology, and disease. FishWorks represents a large-scale co-operative initiative to develop state-of-the-art zebrafish housing, manipulation, genomics and screening infrastructure in Australia. This will both support and further enhance a core group of high quality researchers to engage in cutting-edge research in areas of acknowledged expertise as well as priority within their respective institutions. In addition, it will facilitate wide-ranging collaborative arrangements to further develop and exploit this research area.Read moreRead less
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
Left of centre: Attentional distortions in the mental representation of space in healthy and clinical populations. Stroke patients cost the Australian economy $1.3bn pa in addition to their social burden, but effective diagnosis and rehabilitation is impeded by a lack of fundamental research into the cognitive and neural mechanisms that underlie attentional disorders. Our research will provide significant new insights into how the brain deploys attention in external and imagined space and will l ....Left of centre: Attentional distortions in the mental representation of space in healthy and clinical populations. Stroke patients cost the Australian economy $1.3bn pa in addition to their social burden, but effective diagnosis and rehabilitation is impeded by a lack of fundamental research into the cognitive and neural mechanisms that underlie attentional disorders. Our research will provide significant new insights into how the brain deploys attention in external and imagined space and will lead to more effective management and treatment of stroke victims. Our new test of attentional disorders is independent of a patient's inability to see or move and will enable more effective diagnosis. Our research provides the fundamental knowledge base for our discipline and is vital for developing the next generation of Australia's cognitive neuroscientists. Read moreRead less
Communication and information storage mechanisms in complex dynamical brain networks. Recordings of electrical activity in the brain often cycle repetitively. The aim of this research is to explain how these brain rhythms assist the brain to coordinate simultaneous activity in several regions. Australian socioeconomic benefits include: (i) contributions to the knowledge base of theoretical neuroscience, enhancing Australia's reputation for cutting-edge research; (ii) strengthening of internation ....Communication and information storage mechanisms in complex dynamical brain networks. Recordings of electrical activity in the brain often cycle repetitively. The aim of this research is to explain how these brain rhythms assist the brain to coordinate simultaneous activity in several regions. Australian socioeconomic benefits include: (i) contributions to the knowledge base of theoretical neuroscience, enhancing Australia's reputation for cutting-edge research; (ii) strengthening of international collaborations with Europe and Japan; (iii) outcomes will ultimately impact on improved medical bionics and future interfaces between brain activity and machines or computers; and (iv) commercialization and technology transfer opportunities, via the transfer of results to biologically inspired engineering.Read moreRead less
Identifying novel roles of disease-related proteins in the regulation of exocytosis and nervous communication. This research aims to identify new molecules involved in regulating nerve communication and hormone secretion and which are relevent to human diseases and conditions including Type 2 Diabetes, Down Syndrome, Alzheimer's Disease and Huntington's Disease. The findings may provide new targets in the treatments of such conditions. This research is therefore of special relevance to National ....Identifying novel roles of disease-related proteins in the regulation of exocytosis and nervous communication. This research aims to identify new molecules involved in regulating nerve communication and hormone secretion and which are relevent to human diseases and conditions including Type 2 Diabetes, Down Syndrome, Alzheimer's Disease and Huntington's Disease. The findings may provide new targets in the treatments of such conditions. This research is therefore of special relevance to National Research Priority 2: Promoting and Maintaining Good Health and especially to the sub-areas of this Research Priority 2: Ageing well, ageing productively and Preventative healthcare.Read moreRead less
Ultradian rhythms in basal metabolism; relationship to thermoregulation, cardiovascular function and behavioural arousal. Results from this project will be of basic theoretical biological importance, and may well provide a foundation for understanding basal metabolic regulation and its link with cardiovascular function. Our findings may provide a new foundation for discovering strategies that alter basal metabolic rate in a manner that improves health and reduces the incidence of obesity related ....Ultradian rhythms in basal metabolism; relationship to thermoregulation, cardiovascular function and behavioural arousal. Results from this project will be of basic theoretical biological importance, and may well provide a foundation for understanding basal metabolic regulation and its link with cardiovascular function. Our findings may provide a new foundation for discovering strategies that alter basal metabolic rate in a manner that improves health and reduces the incidence of obesity related disease such as heart attack and stroke. Thus this research proposal is of special relevance to National Research Priority 2: Promoting and Maintaining Good Health. Obesity and obesity-related medical conditions particularly affect older people, so that our research is also highly relevant to National Research Priority 2 sub-areas: Ageing well, Ageing productively.Read moreRead less
Single and dual process models of recognition memory: Reconciliation of behavioural, electrophysiological, and neuroimaging data. Advanced brain scanning technologies are increasingly used to study human memory. As well as being important for our basic understanding of memory, they also tell us how memory is affected by normal development, ageing, disease, and injury. Unfortunately, because these technologies are so new, a gap has opened up between our psychological understanding of memory and t ....Single and dual process models of recognition memory: Reconciliation of behavioural, electrophysiological, and neuroimaging data. Advanced brain scanning technologies are increasingly used to study human memory. As well as being important for our basic understanding of memory, they also tell us how memory is affected by normal development, ageing, disease, and injury. Unfortunately, because these technologies are so new, a gap has opened up between our psychological understanding of memory and the physiological events measured by the scanning technologies. This has created a problem for how we should interpret the results that are found. The present project aims to close this gap by applying new research methodologies and theoretical insights based on our previous research.Read moreRead less