Understanding The Role And Mechanism Of Interaction Of Small Heat-shock Proteins In Age-related Disease
Funder
National Health and Medical Research Council
Funding Amount
$270,827.00
Summary
Protein precipitation is associated with a diversity of age-related diseases such as cataract and Alzheimer's. Within cells, a group of chaperones called the small heat-shock proteins (sHSPs) function by binding to destabilized proteins, however, common in vivo modifications can disrupt their cellular role leading to co-aggregation in a number of age-related diseases. This study will use state of the art mass spectrometry to examine the mechanism by which sHSPs interact with client proteins.
Investigating The Iron Proteome In Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$514,644.00
Summary
Iron is essential for brain function. When the delicate balance of metals in the brain is disturbed, neurodegenerative effects such as those seen in Alzheimer’s disease are observed. Although we know there is a link between iron and Alzheimer’s disease, we do not know which specific iron proteins are involved. This project will provide the first characterisation of different iron proteins in the brain to understand the mechanisms of disease and help in the search for new treatments.
Role of the proteasome in eradication of misfolded proteins in fungal cell factories. Filamentous fungi contribute to the well being of modern society as surrogate hosts for the synthesis of vaccines, hormones and enzymes for their application to health, agriculture, industry and the environment. However, attempts to express foreign proteins to the full potential of a given system have been disappointing. It is vital to understand unexplored molecular and physiological factors such as protein ....Role of the proteasome in eradication of misfolded proteins in fungal cell factories. Filamentous fungi contribute to the well being of modern society as surrogate hosts for the synthesis of vaccines, hormones and enzymes for their application to health, agriculture, industry and the environment. However, attempts to express foreign proteins to the full potential of a given system have been disappointing. It is vital to understand unexplored molecular and physiological factors such as protein quality control in the cell to take advantage of the global opportunities that recombinant gene expression indisputably offers in the form of unrestricted supply of proteins of social and economic value. The project will create novel IP and licensing opportunities for Australia.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561041
Funder
Australian Research Council
Funding Amount
$347,358.00
Summary
A New Generation Biosensor and Fluorescence Facility for Proteomics. The complete DNA sequence (the genome) is now known for many organisms and advances are being made to identify the complement of messenger RNA (the transcriptome) and the resultant collection of proteins (the proteome). The genome is largely fixed while the transcriptome and proteome differ between cell types in an organism and constantly vary to adapt the cell to changing conditions. The mediators of these variations are prote ....A New Generation Biosensor and Fluorescence Facility for Proteomics. The complete DNA sequence (the genome) is now known for many organisms and advances are being made to identify the complement of messenger RNA (the transcriptome) and the resultant collection of proteins (the proteome). The genome is largely fixed while the transcriptome and proteome differ between cell types in an organism and constantly vary to adapt the cell to changing conditions. The mediators of these variations are proteins, interacting with each other and with signal molecules. The next frontier in molecular biology is to identify and quantify these protein interactions. Our two institutions have a very large cohort of biologists whose research on proteins would be greatly facilitated by the Biacore 3000 and the ISS K2.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100125
Funder
Australian Research Council
Funding Amount
$330,000.00
Summary
Oxidative stress bioanalytical facility. The primary national benefit of this application is that it will provide a currently unavailable, state-of-the-art facility for Australian scientists to define precisely how changes in cellular redox state contribute to biological processes relevant to health and diseases. The facility will uniquely complement, and in many cases integrate with existing facilities in this area of research in Australia. It will act as a platform for major national and inter ....Oxidative stress bioanalytical facility. The primary national benefit of this application is that it will provide a currently unavailable, state-of-the-art facility for Australian scientists to define precisely how changes in cellular redox state contribute to biological processes relevant to health and diseases. The facility will uniquely complement, and in many cases integrate with existing facilities in this area of research in Australia. It will act as a platform for major national and international research collaborations, develop cutting-edge technology and unique local skills, and contribute to Australia maintaining a leading position in redox-related research in biology and medicine. In doing so, the facility will increase the likelihood of gaining future, value-adding funding.Read moreRead less
Identifying The Targets Of Myeloperoxidase-derived Oxidants In Plasma And Cells
Funder
National Health and Medical Research Council
Funding Amount
$237,258.00
Summary
Myeloperoxidase (MPO) is a haem enzyme, released by activated white blood cells, that catalyses the production of highly damaging chlorinated oxidants. These oxidants are known to play a major role in the human immune system by killing bacteria and other invading pathogens. However, excessive or misplaced generation of these oxidants results in tissue damage. This damage has been implicated in development of disease. For example, there is strong evidence for the involvement of MPO, and the oxida ....Myeloperoxidase (MPO) is a haem enzyme, released by activated white blood cells, that catalyses the production of highly damaging chlorinated oxidants. These oxidants are known to play a major role in the human immune system by killing bacteria and other invading pathogens. However, excessive or misplaced generation of these oxidants results in tissue damage. This damage has been implicated in development of disease. For example, there is strong evidence for the involvement of MPO, and the oxidants that it produces, in atherosclerosis. This disease is responsible for the death of around 40 % of the Australian population. There is no doubt that the oxidants produced by MPO cause major damage to tissues and extensive cell death. However, the mechanisms involved in this process remain to be established, due to a lack of sensitive and specific techniques for examining oxidant-mediated damage to individual target molecules. This study will identify the key targets of MPO-derived oxidants in plasma and cells using novel labelling techniques. This will provide valuable information about the mechanisms of oxidative damage and cytotoxicity. This will be important in the design of potential therapeutic agents to modulate and prevent the progression of degenerative diseases, such as atherosclerosis, that are linked with MPO.Read moreRead less
From genotype to phenotype - systems biology bridging the gap. This project is basic research at the forefront of international science and deals with a fundamental question of modern biology: 'How do genes determine the makeup of an organism?' The main outcome will be a deeper understanding of the internal working mechanisms of a higher organism. The project combines some of the most advanced systems technologies - genomics, proteomics, metabonomics, fluxomics and computational biology in a nov ....From genotype to phenotype - systems biology bridging the gap. This project is basic research at the forefront of international science and deals with a fundamental question of modern biology: 'How do genes determine the makeup of an organism?' The main outcome will be a deeper understanding of the internal working mechanisms of a higher organism. The project combines some of the most advanced systems technologies - genomics, proteomics, metabonomics, fluxomics and computational biology in a novel and unique way. This combination is in itself a major advancement of scientific methods that will accelerate discovery in the field of systems biology. In this respect, the project is a premier example of the priority goal Breakthrough Science and of the national research priority Frontier Technologies.Read moreRead less
Multi-functional probes for global analysis of proteome stress in cells. This project aims to create a suite of multi-functional chemical probes to identify damaged proteins that undergo unfolding or specific modifications in cells under stress. These probes will not only generate fluorescence responses to reflect on protein quality control capacity but allow associated proteins and their networks to be identified in complex cellular environments, which is difficult to achieve by current methods ....Multi-functional probes for global analysis of proteome stress in cells. This project aims to create a suite of multi-functional chemical probes to identify damaged proteins that undergo unfolding or specific modifications in cells under stress. These probes will not only generate fluorescence responses to reflect on protein quality control capacity but allow associated proteins and their networks to be identified in complex cellular environments, which is difficult to achieve by current methods. The expected outcome is to deliver new methodology for a comprehensive understanding of the correlation between quality control machinery, stress responses and cell functions. This should provide significant benefits, including contributing to fundamental knowledge on the molecular causes of neurodegenerative diseases.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0237729
Funder
Australian Research Council
Funding Amount
$735,000.00
Summary
A proteomics facility for Queensland researchers. The successful completion of sequencing of the genomes of many organisms, including man, has thrown emphasis back on the identification of proteins involved in the complex events that sustain cellular life. Our aim is to set up a world-class facility for proteomics research which will allow a large cohort of scientists at several institutions to identify individual proteins in vanishingly small samples of very complex mixtures. This facility wi ....A proteomics facility for Queensland researchers. The successful completion of sequencing of the genomes of many organisms, including man, has thrown emphasis back on the identification of proteins involved in the complex events that sustain cellular life. Our aim is to set up a world-class facility for proteomics research which will allow a large cohort of scientists at several institutions to identify individual proteins in vanishingly small samples of very complex mixtures. This facility will enable investigation of the control of gene expression, the intricate organisation of proteins within cells, and proteins which are potential drug targets. This equipment is an essential resource for Queensland research groups.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100080
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Examining lipid transport by direct visualisation and quantification. This project aims to investigate the least understood aspect of plasma triglyceride metabolism; mechanisms of transport across capillary endothelial cells. This transport regulates plasma triglyceride levels, which are an important factor in determining risk for coronary diseases. An improved understanding of these mechanisms will lead in the long term to better understandings of both heart failure and atherosclerotic heart di ....Examining lipid transport by direct visualisation and quantification. This project aims to investigate the least understood aspect of plasma triglyceride metabolism; mechanisms of transport across capillary endothelial cells. This transport regulates plasma triglyceride levels, which are an important factor in determining risk for coronary diseases. An improved understanding of these mechanisms will lead in the long term to better understandings of both heart failure and atherosclerotic heart diseases.Read moreRead less