The Role of Amyloid Protein Precursor in Mammalian Copper Transport. The knowledge gained from this investigation will help us to develop new medicines for the treatment of debilitating and ever more prevalent age-related neurodegenerative diseases and will help us to illuminate the role of metals in the ageing process itself. Apart from the obvious economic and social benefits in extending the productive lifetime of its citizens, the outcomes of this project have clear commercial applications. ....The Role of Amyloid Protein Precursor in Mammalian Copper Transport. The knowledge gained from this investigation will help us to develop new medicines for the treatment of debilitating and ever more prevalent age-related neurodegenerative diseases and will help us to illuminate the role of metals in the ageing process itself. Apart from the obvious economic and social benefits in extending the productive lifetime of its citizens, the outcomes of this project have clear commercial applications. We anticipate that there will be patents that will ensue from the programme, which will be licensed to Australian interests, and contribute to the national revenue in the biotechnology and pharmaceutical sector.Read moreRead less
Neural Copper Homeostasis: the role of the Alzheimer Amyloid-beta Precursor Protein. Alzheimer's disease (AD) is creating a growing burden upon Australian medical resources. Copper plays an important role in the development of AD, and drugs designed to adjust brain copper levels are being tested for AD treatment and show therapeutic benefits. This project will determine how copper is involved in AD so that more effective drugs can be developed. Focus will primarily be on copper-binding proteins ....Neural Copper Homeostasis: the role of the Alzheimer Amyloid-beta Precursor Protein. Alzheimer's disease (AD) is creating a growing burden upon Australian medical resources. Copper plays an important role in the development of AD, and drugs designed to adjust brain copper levels are being tested for AD treatment and show therapeutic benefits. This project will determine how copper is involved in AD so that more effective drugs can be developed. Focus will primarily be on copper-binding proteins central to AD, including amyloid-beta, and their role in AD development. Upon completion of this project, we expect to better understand neural copper metabolism in health and in AD pathology, with outcomes directly applicable to therapeutic AD intervention.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.
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
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
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100226
Funder
Australian Research Council
Funding Amount
$424,000.00
Summary
Advanced molecular discovery and characterisation facility. Natural product drug discovery in Australia requires access to high throughput functional assays to guide the separation and of novel bioactives with therapeutic potential. By establishing the advanced molecular discovery and characterisation facility in an academic environment across two institutions, research programs in early drug lead discovery and characterisation will be accelerated. It will provide unique capabilities not curren ....Advanced molecular discovery and characterisation facility. Natural product drug discovery in Australia requires access to high throughput functional assays to guide the separation and of novel bioactives with therapeutic potential. By establishing the advanced molecular discovery and characterisation facility in an academic environment across two institutions, research programs in early drug lead discovery and characterisation will be accelerated. It will provide unique capabilities not currently available in Australia, and help Australian researchers remain internationally competitive in breakthrough science and frontier technologies. The research enabled by this facility will lead to development of new drug candidates by the emerging Australian biotechnology industry.Read moreRead less