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
Oxidation Of Arterial Extracellular Matrix By Myeloperoxidase-derived Oxidants
Funder
National Health and Medical Research Council
Funding Amount
$183,266.00
Summary
It is well established that changes occur in the composition and nature of the extracellular matrix present in the artery wall during the development of atherosclerosis. The changes that occur in this matrix affect both the mechanical and physical properties of the arterial wall (e.g. its ability to cope with the high pressures genrated by the pumping of blood from the heart) and the adhesion of cells. It is well established that certain key cell types do not adhere well, or grow properly, on al ....It is well established that changes occur in the composition and nature of the extracellular matrix present in the artery wall during the development of atherosclerosis. The changes that occur in this matrix affect both the mechanical and physical properties of the arterial wall (e.g. its ability to cope with the high pressures genrated by the pumping of blood from the heart) and the adhesion of cells. It is well established that certain key cell types do not adhere well, or grow properly, on altered or damaged matrix and this can result in either the loss of key cell types from the artery wall (e.g. loss of endothelial cells) and - or the proliferation and invasion of cells from other sources (e.g. smooth muscle cell invasion into the intimal space). There is circumstantial evidence that some of these changes occur via the formation of oxidants by the heme enzyme myeloperoxidase which is released from activated white cells. In this study we will employ recently developed analytical techniques to examine the nature of the alterations that are present in atherosclerotic plaques in comparison to normal human artery samples, and investigate the mechanisms by which such alterations arise. We will seek evidence for, or against, the involvement of myeloperoxidase-derived oxidants in the observed changes using specific markers which we have developed for the presence of such damage. This information will allow the rational design of strategies to interfere with the progression of atherosclerosis, which is the major killer of Australians.Read moreRead less
Identifying novel salinity tolerance mechanisms by spatial and temporal analysis of lipids in barley. Agrifood production faces the dual challenges of an increasing world population and the threats of abiotic stresses arising from climate change and the erosion of arable land. Cereals, the major food crops, are poorly adapted to tolerate most abiotic stresses, including salinity. This project applies new technologies investigating spatial and temporal biochemical mechanisms a model cereal, Horde ....Identifying novel salinity tolerance mechanisms by spatial and temporal analysis of lipids in barley. Agrifood production faces the dual challenges of an increasing world population and the threats of abiotic stresses arising from climate change and the erosion of arable land. Cereals, the major food crops, are poorly adapted to tolerate most abiotic stresses, including salinity. This project applies new technologies investigating spatial and temporal biochemical mechanisms a model cereal, Hordeum vulgare (barley), utilises to adapt and tolerate salinity. The aims are to investigate the role of specifically plasma membrane lipids modulating either signalling pathways or membrane fluidity that impacts on adaptation during salinity. The results will provide new leads for the development of cereal germplasm with increased salt tolerance.Read moreRead less
All-in-vitro engineering and single molecule analysis of protein complexes. The production and engineering of proteins are key methodologies in life sciences. The current project aims to develop new approaches to accelerate the production and analysis of proteins and to apply them to increase our understanding of the basic mechanisms of cell self-maintenance.
Regulation of proteolysis by specialised adaptor proteins. Training research scientists of the future forms an integral part of this research program and this collaboration will provide an excellent opportunity for young Australian scientists to be exposed to the very professional and competitive environment of basic research, as it exists in Germany. It will expose early career researchers to new ideas and emerging methodologies arming them with valuable skills, which they will transfer to Aust ....Regulation of proteolysis by specialised adaptor proteins. Training research scientists of the future forms an integral part of this research program and this collaboration will provide an excellent opportunity for young Australian scientists to be exposed to the very professional and competitive environment of basic research, as it exists in Germany. It will expose early career researchers to new ideas and emerging methodologies arming them with valuable skills, which they will transfer to Australia. The involvement of Prof. Turgay in the Deutsche Forschungsgemeinschaft (DFG) Priority Programme: Proteolysis in Prokaryotes also provides a unique opportunity for these young researchers to interact with several of the worlds leading scientists in the area of proteolysis, enhancing Australia's reputation at the forefront of science.Read moreRead less
Carbon flux and its regulation in metabolic networks. Allocation of photo-assimilates throughout metabolic networks are central to a plants ability to cope with changes in its environment. This project will combine the use of quantitative molecular, chemical and imaging techniques to characterise the flux of resources and its regulation through metabolic networks of Australian native and crop plants.
Unravelling transthyretin amyloid, bounding ahead using wallabies. Each protein in our body has a unique shape that enables it to function correctly. For unknown reasons, some proteins can change their shape, aggregate with other proteins and stick to the outside of cells of major organs or nerves. This prevents those cells from working properly and results in disease. Transthyretin is a protein that changes shape and aggregates in the heart of most people over the age of 70. The disease is call ....Unravelling transthyretin amyloid, bounding ahead using wallabies. Each protein in our body has a unique shape that enables it to function correctly. For unknown reasons, some proteins can change their shape, aggregate with other proteins and stick to the outside of cells of major organs or nerves. This prevents those cells from working properly and results in disease. Transthyretin is a protein that changes shape and aggregates in the heart of most people over the age of 70. The disease is called Senile Systemic Amyloidosis (SSA). It is not known how or why this happens. There is no cure or therapy. This project will use transthyretins from human and wallaby to explore a possible cause of SSA. If our hypothesis is correct, we will propose preventative actions to reduce the incidence of SSA in the future.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE200100183
Funder
Australian Research Council
Funding Amount
$950,000.00
Summary
Protein Quantitation Centre of South Australia renewal for Systems Biology. This application aims to renew Mass Spectrometry (MS) instrumentation to characterise and quantify Biomolecules towards a better understanding of biological processes. UniSA, Uni Adelaide, Flinders have established the Protein Quantitation Centre of South Australia (PQCSA) in 2013 through an ARC LIEF lead by CI Hoffmann and this application will renew and expand MS capacity towards metabolites, glycans and lipids. This ....Protein Quantitation Centre of South Australia renewal for Systems Biology. This application aims to renew Mass Spectrometry (MS) instrumentation to characterise and quantify Biomolecules towards a better understanding of biological processes. UniSA, Uni Adelaide, Flinders have established the Protein Quantitation Centre of South Australia (PQCSA) in 2013 through an ARC LIEF lead by CI Hoffmann and this application will renew and expand MS capacity towards metabolites, glycans and lipids. This will enable researchers in South Australia to work towards a full understanding of biological processes and towards expanding their knowledge to Systems Biology. Expected outcome of the projects are multiple interdisciplinary collaborations between the CI's and should provide significant benefits in research outputs.Read moreRead less
Metalloproteomics: A new piece of the systems biology puzzle. Systems biology uses advanced analytical technology to study the complex chemistry of the living cell. Many cellular functions are the result of chemical reactions involving metalloproteins, which are notoriously difficult to study due to the weak bonds between metal and protein that is not normally amenable to traditional proteomic approaches. In partnership with the leading analytical manufacturer Agilent Technologies, this project ....Metalloproteomics: A new piece of the systems biology puzzle. Systems biology uses advanced analytical technology to study the complex chemistry of the living cell. Many cellular functions are the result of chemical reactions involving metalloproteins, which are notoriously difficult to study due to the weak bonds between metal and protein that is not normally amenable to traditional proteomic approaches. In partnership with the leading analytical manufacturer Agilent Technologies, this project aims to adapt and apply advanced mass spectrometry to the study of metalloproteins, developing new methods for studying hundreds of molecules in single experiments. Using the C. elegans model organism the project aims to showcase the importance of metals in biology and develop new solutions for the $2.9 billion proteomics industry.Read moreRead less
Function and modulation of the protein quality control network in mammalian mitochondria. This project has potential technological benefit in the areas of biotechnology and molecular medicine especially in relation to age-related cellular degeneration. As a result of our research outputs, strategies could be developed to either delay the onset or reduce the severity of diseases related to mitochondrial dysfunction. Training research scientists of the future, forms an integral part of our researc ....Function and modulation of the protein quality control network in mammalian mitochondria. This project has potential technological benefit in the areas of biotechnology and molecular medicine especially in relation to age-related cellular degeneration. As a result of our research outputs, strategies could be developed to either delay the onset or reduce the severity of diseases related to mitochondrial dysfunction. Training research scientists of the future, forms an integral part of our research program and our association with world leaders in the field provide excellent opportunity for exchange of personnel, ideas and emerging methodologies. This project will lead the way in this field and consequently will expand Australia's reputation at the forefront of scientific advancement. Read moreRead less