Role Of Transition Metal Ions And Redox Activity In The Development Of Atherosclerotic Plaques
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability ....Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability to generate free radicals is controversial. This study will employ a novel, minimally-invasive, technique to assess the nature and quantity of metal ions present in well-defined human and animal lesions at different stages of lesion development. The ability of these metal ions to catalyse free radical formation from components present in the artery wall will also be assessed. The release of these metal ions from the artery wall to added organic molecules will be assessed as this might minimise their potential to cause damage, and provide a possible therapeutic strategy. These studies will therefore provide valuable information as to the significance and role of reactive metal ions in the development of human artery disease and the possible prevention, or minimisation, of such processes.Read moreRead less
Mitochondrial Iron Overload And Friedreich's Ataxia: The Role Of Frataxin In Iron And Haem Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$606,000.00
Summary
Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. A variety of studies using Baker's yeast and conditional frataxin knockout (KO) mice have shown that deletion of frataxin leads to the accumulation of toxic iron in their mitochondrion. More recently, a variety of studies have shown that FA patients have iron-loading within their mitochondrion. Iron in the highly redox active environment of the mitochondrion could contribute to the generation of cytotoxic radicals that c ....Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. A variety of studies using Baker's yeast and conditional frataxin knockout (KO) mice have shown that deletion of frataxin leads to the accumulation of toxic iron in their mitochondrion. More recently, a variety of studies have shown that FA patients have iron-loading within their mitochondrion. Iron in the highly redox active environment of the mitochondrion could contribute to the generation of cytotoxic radicals that cause severe damage. Further, cells deficient in frataxin are sensitive to oxidant stress and Fe chelators rescue oxidant-mediated death of cells from FA patients. Indeed, free radical scavengers have shown to be of use in the treatment of this disease. Studies in DR's lab during this NHMRC grant have shown that frataxin is down-regulated by erythroid differentiation or the haem precursor, protoporphyrin IX (BLOOD 2002;99:3813-22). These data indicate a role for frataxin in Fe metabolism and the pathogenesis of FA. In this study we will continue to examine the role of frataxin in the way cells handle Fe using experimental models developed under the current NHMRC grant. These include transfected cell lines with low frataxin expression generated using an expression vector containing anti-sense frataxin cDNA. Further we obtained the frataxin conditional KO mouse and generated a breeding colony. These animals display many of the pathological features of FA and are the best current model of the disease. Indeed, they will be critical for assessing the role of frataxin in Fe metabolism and as a model to test the ability of Fe-binding drugs to prevent the pathology observed. We designed lipid-soluble chelators that can enter the mitochondrion to bind Fe (Biochim Biophys Acta 2001;1536:133-140) and these ligands will be tested to prevent disease progression in the KO mice. This exciting research is crucial for understanding the pathogenesis of FA and in creating new therapies.Read moreRead less
Rubisco for all climates: unlocking the enzyme's structure-function relations for more efficient photosynthesis. This projects biotechnological research will identify structural features in the carbon dioxide (CO2)-capturing enzyme from plants that improve its performance, particularly at warmer temperatures. This knowledge is vital for predicting the influence of climate change on crop productivity and paving the way for supercharging photosynthesis to boost crop performance.
The role of neutral amino acid transport in normal physiology. Future benefits of these studies include the Promotion and Maintenance of Good Health achieved by providing: (1) a better understanding of brain and balance disorders; (2) insights into the damaging effects of the sun and; (3) existing neonatal screening programmes for Hartnup disorder with greater scientific foundation regarding the implications of inheriting this condition, including dietary advce. We will be able to provide Austr ....The role of neutral amino acid transport in normal physiology. Future benefits of these studies include the Promotion and Maintenance of Good Health achieved by providing: (1) a better understanding of brain and balance disorders; (2) insights into the damaging effects of the sun and; (3) existing neonatal screening programmes for Hartnup disorder with greater scientific foundation regarding the implications of inheriting this condition, including dietary advce. We will be able to provide Australians who inherit Hartnup disorder with a better understanding of this disease by enabling individuals and families to make choices that lead to healthy, productive and fulfilling lives.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE170100192
Funder
Australian Research Council
Funding Amount
$450,000.00
Summary
Deep Protein Sequencing, Structure and Quantification Facility. This project aims to establish state-of-the-art complementary mass spectrometers to help research into molecular structure and interactions, post-translational modifications, compound stability and availability within complex biological samples. The facility’s complementary mass spectrometers combine high specificity with high sensitivity and ultrafast scanning, and are expected to rapidly discover, identify and characterise biomole ....Deep Protein Sequencing, Structure and Quantification Facility. This project aims to establish state-of-the-art complementary mass spectrometers to help research into molecular structure and interactions, post-translational modifications, compound stability and availability within complex biological samples. The facility’s complementary mass spectrometers combine high specificity with high sensitivity and ultrafast scanning, and are expected to rapidly discover, identify and characterise biomolecules including peptides, proteins and small molecules. The discovery of unknown compounds is expected to improve fundamental understanding of molecular structure and function, provide opportunities for new bio-industries in health and the environment, and generate commercial opportunities through spin-off companies, patents and licensing.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100142
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
An integrated liquid chromatography mass spectrometry nuclear magnetic resonance (LC-MS-NMR) facility for applications in proteomics and organic chemistry. This application completes the requested liquid chromatography mass spectrometry nuclear magnetic resonance (LCMS-NMR) facility and will allow the training of over 150 researchers, significantly enhancing their research productivity and translation of outcomes in areas of national importance. New breakthroughs in drug development, smart mate ....An integrated liquid chromatography mass spectrometry nuclear magnetic resonance (LC-MS-NMR) facility for applications in proteomics and organic chemistry. This application completes the requested liquid chromatography mass spectrometry nuclear magnetic resonance (LCMS-NMR) facility and will allow the training of over 150 researchers, significantly enhancing their research productivity and translation of outcomes in areas of national importance. New breakthroughs in drug development, smart materials, organic electronic materials and biomedical research require routine access to cutting edge technology. The LCMS-NMR augments the capabilities of our research teams at the forefront of these efforts. These include understanding the impact of the environment on plant and animal development, pest animal control, development of new biotechnology tools, new drugs and new methods for the detection of narcotics and explosives.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100078
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
Establishment of a comprehensive regional biophysical analysis facility. Interactions between molecules are needed for cells to function correctly. This facility will permit comprehensive molecular characterisation as well as research into the fundamentals of how molecules interact.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100174
Funder
Australian Research Council
Funding Amount
$800,000.00
Summary
Innovative synchrotron science - program for access to the Australian National Beamline Facility and cutting-edge beamlines at international synchrotrons. Synchrotron science dramatically affects the community through the innovative scientific, engineering and medical research outcomes it produces. This program for access to synchrotron beamlines is aimed at enhancing Australia's high international standing in synchrotron science and will have many flow-on effects in areas such as health and ind ....Innovative synchrotron science - program for access to the Australian National Beamline Facility and cutting-edge beamlines at international synchrotrons. Synchrotron science dramatically affects the community through the innovative scientific, engineering and medical research outcomes it produces. This program for access to synchrotron beamlines is aimed at enhancing Australia's high international standing in synchrotron science and will have many flow-on effects in areas such as health and industry.Read moreRead less