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
Industrial Transformation Research Hubs - Grant ID: IH220100017
Funder
Australian Research Council
Funding Amount
$4,808,669.00
Summary
ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals. Radiopharmaceuticals are emerging as next generation medical technologies for addressing complex health challenges, and their manufacture offers significant economic benefit to Australia. The ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals (AMTAR) aims to establish a manufacturing platform for new medical technologies combining innovations in biotechnology and pharmaceutical science. The progra ....ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals. Radiopharmaceuticals are emerging as next generation medical technologies for addressing complex health challenges, and their manufacture offers significant economic benefit to Australia. The ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals (AMTAR) aims to establish a manufacturing platform for new medical technologies combining innovations in biotechnology and pharmaceutical science. The program addresses industry-led challenges for translation of biologics as molecular radiopharmaceuticals, building capacity in biomanufacturing, radiobiology and radiochemistry. The program establishes a dedicated manufacturing pipeline, future-proofing production and securing supply chain of next generation medical technologies.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
ARC Centre of Excellence in Plants for Space. ARC Centre of Excellence in Plants for Space. This Centre aims to create on-demand, zero-waste, high-efficiency plants and plant products to address grand challenges in sustainability for Space and on Earth. Significant advances in plant, food, and sensory science; process and systems engineering; law and policy; and psychology are expected to deliver transformative solutions for Space habitation – and create enhanced plant-derived food and bioresour ....ARC Centre of Excellence in Plants for Space. ARC Centre of Excellence in Plants for Space. This Centre aims to create on-demand, zero-waste, high-efficiency plants and plant products to address grand challenges in sustainability for Space and on Earth. Significant advances in plant, food, and sensory science; process and systems engineering; law and policy; and psychology are expected to deliver transformative solutions for Space habitation – and create enhanced plant-derived food and bioresources to capitalise upon emergent and rapidly expanding domestic and global markets. Anticipated outcomes include industry uptake of innovative plant forms, foods, technologies, and commodities; and an ambitious education and international co-ordination agenda to position Australia as a global leader in research supporting Space habitation.Read moreRead less
ARC Centre of Excellence for Innovations in Peptide and Protein Science. The ARC Centre of Excellence for Innovations in Peptide and Protein Science (CIPPS) strives to build a critical understanding of peptides and proteins in order to unleash the potential of these biomolecules for human benefit. We will discover nature’s untapped reservoir of peptides and proteins, decode their structures and functions, and
develop enhanced synthetic technologies to address biology’s next grand challenge—the d ....ARC Centre of Excellence for Innovations in Peptide and Protein Science. The ARC Centre of Excellence for Innovations in Peptide and Protein Science (CIPPS) strives to build a critical understanding of peptides and proteins in order to unleash the potential of these biomolecules for human benefit. We will discover nature’s untapped reservoir of peptides and proteins, decode their structures and functions, and
develop enhanced synthetic technologies to address biology’s next grand challenge—the design of peptides and proteins for targeted scientific, agricultural, biotechnology, animal health and pharmaceutical applications. CIPPS will assemble leading researchers from diverse disciplines to create a sustainable national entity that will drive new Australian industries and train next generation researchers.Read moreRead less
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