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
Molecular Investigations into Polyglutamine Repeat Proteins. The proposed research program, will provide significant fundamental insight into the processes that control protein aggregation and disease. Investigating processes central to protein aggregation is important, as it will further our understanding of these critically-important events and our understanding of disease processes. Such knowledge will increase Australia's international research standing, as well as having the potential to ....Molecular Investigations into Polyglutamine Repeat Proteins. The proposed research program, will provide significant fundamental insight into the processes that control protein aggregation and disease. Investigating processes central to protein aggregation is important, as it will further our understanding of these critically-important events and our understanding of disease processes. Such knowledge will increase Australia's international research standing, as well as having the potential to generate novel therapies, that prevent neurodegeneration.Read moreRead less
Analysing the detrimental effects of polyglutamine expansion. The proposed research program, will provide significant fundamental insight into the processes that control protein aggregation and its link with disease. Investigating processes central to protein aggregation is important as it will deepen our understanding of how proteins inappropriately change shape and our understanding of disease processes. Such knowledge will increase Australia's international research standing, as well as ha ....Analysing the detrimental effects of polyglutamine expansion. The proposed research program, will provide significant fundamental insight into the processes that control protein aggregation and its link with disease. Investigating processes central to protein aggregation is important as it will deepen our understanding of how proteins inappropriately change shape and our understanding of disease processes. Such knowledge will increase Australia's international research standing, as well as having the potential to generate novel therapies, that prevent neurodegeneration.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100036
Funder
Australian Research Council
Funding Amount
$470,000.00
Summary
A protein molecular interaction and localization facility. This proposal will address a major gap in our mass spectrometry capabilities and aid in our understanding of protein interactions and tissue distribution in areas such as neuroscience, microbiology, immunology, and botany, as well as enhance our understanding of fundamental gas phase chemistry of protein molecules. It brings together a highly successful multidisciplinary team of high-profile researchers with a track record of collaborati ....A protein molecular interaction and localization facility. This proposal will address a major gap in our mass spectrometry capabilities and aid in our understanding of protein interactions and tissue distribution in areas such as neuroscience, microbiology, immunology, and botany, as well as enhance our understanding of fundamental gas phase chemistry of protein molecules. It brings together a highly successful multidisciplinary team of high-profile researchers with a track record of collaboration and delivering outcomes from shared facilities. In addition to these key scientific outcomes this project will also facilitate the training of several new personnel in a skill area for which there is a critical shortage (mass spectrometry) and promote true cross-disciplinary skills.Read moreRead less
O-GlcNAc-phosphorylation: a novel post-translational modification regulating vesicle recycling. We will determine a biological role for our discovery of a hybrid protein modification (both carbohydrate and phosphate) on a brain protein that is involved in nerve cell communication. If this modification is more widespread, then we will have discovered a new level of cellular regulation. This discovery is likely to have a broad benefit. It will advance the understanding of carbohydrate and phosphat ....O-GlcNAc-phosphorylation: a novel post-translational modification regulating vesicle recycling. We will determine a biological role for our discovery of a hybrid protein modification (both carbohydrate and phosphate) on a brain protein that is involved in nerve cell communication. If this modification is more widespread, then we will have discovered a new level of cellular regulation. This discovery is likely to have a broad benefit. It will advance the understanding of carbohydrate and phosphate modified proteins. For example, there may be consequences for the model of hyperphosphorylated and carbohydrate modified proteins involved in neurodegeneration. There will also be a targeted benefit. An improved understanding of the mechanism of neurotransmission will benefit in designing compounds to fight diseases of neurotransmission.Read moreRead less
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
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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Biological probes for understanding mammalian cellular transport mechanisms. Cellular components are moved around within cells by molecular motors. This fundamental transport mechanism depends on a network of tracks. Blocks in this cellular transport can result in a number of mammalian diseases, particularly within nerve cells. This project will increase our understanding of the mechanisms of cellular transport and, in particular, how molecular motors engage their cargo. This is essential ground ....Biological probes for understanding mammalian cellular transport mechanisms. Cellular components are moved around within cells by molecular motors. This fundamental transport mechanism depends on a network of tracks. Blocks in this cellular transport can result in a number of mammalian diseases, particularly within nerve cells. This project will increase our understanding of the mechanisms of cellular transport and, in particular, how molecular motors engage their cargo. This is essential groundwork for the development of drugs that target this transport mechanism.Read moreRead less
Role of the GxxxG domain in the function of mammalian prion proteins. Prion proteins have been associated with a number of diseases of humans and animals (such as Creutzfeldt-Jakob Disease in humans and BSE, or 'mad-cow' disease in cattle) which have had major public health, social and economic consequences in countries where they have been detected. This project will identify mechanisms by which a highly conserved region of the prion protein plays a role in the conversion to the disease associa ....Role of the GxxxG domain in the function of mammalian prion proteins. Prion proteins have been associated with a number of diseases of humans and animals (such as Creutzfeldt-Jakob Disease in humans and BSE, or 'mad-cow' disease in cattle) which have had major public health, social and economic consequences in countries where they have been detected. This project will identify mechanisms by which a highly conserved region of the prion protein plays a role in the conversion to the disease associated form. This will provide avenues for identifying the normal function of the prion protein, and increase our knowledge of prion biology. This will benefit both in terms of healthy ageing and in protecting the agriculture sector from prion diseases in farmed animals.Read moreRead less
Cracking the LIM-code: Transcription factor networks in developmental biology. Our current inability to stimulate the regeneration of nervous tissue is frustrated by a lack of detailed knowledge of the complex processes that take place at the molecular and cellular levels during development. We are determining how a group of cellular proteins that have key roles in neural development interact with each other and with DNA. With this information we are developing reagents that can be used to probe ....Cracking the LIM-code: Transcription factor networks in developmental biology. Our current inability to stimulate the regeneration of nervous tissue is frustrated by a lack of detailed knowledge of the complex processes that take place at the molecular and cellular levels during development. We are determining how a group of cellular proteins that have key roles in neural development interact with each other and with DNA. With this information we are developing reagents that can be used to probe the fundamental process of cell differentiation in the central nervous system.Read moreRead less