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
HARMONIC ANALYSIS AND BOUNDARY VALUE PROBLEMS FOR ELLIPTIC SYSTEMS. It is of the utmost necessity for Australia to develop the theoretical
expertise needed in the current era. The type of mathematics under
investigation here is closely allied to that needed in much of the
current boom in communication technology and medical research. The
training which would be provided to the research associates is
considerable, and would flow on to produce the expertise needed to
keep the coming gen ....HARMONIC ANALYSIS AND BOUNDARY VALUE PROBLEMS FOR ELLIPTIC SYSTEMS. It is of the utmost necessity for Australia to develop the theoretical
expertise needed in the current era. The type of mathematics under
investigation here is closely allied to that needed in much of the
current boom in communication technology and medical research. The
training which would be provided to the research associates is
considerable, and would flow on to produce the expertise needed to
keep the coming generation involved in modern technological development. I will maintain my large collaborative effort with
leading mathematicians from the US, France and other countries, thus
helping to keep Australia at the forefront of a significant field of
research.Read moreRead less
HARMONIC ANALYSIS OF ELLIPTIC SYSTEMS ON RIEMANNIAN MANIFOLDS. It is of the utmost necessity for Australia to develop the theoretical expertise needed in the current era. The type of mathematics under investigation here is closely allied to that needed in much of the current boom in communication technology and medical research. The training which would be provided to the research associates is considerable, and would flow on to produce the expertise needed to keep the coming generation invol ....HARMONIC ANALYSIS OF ELLIPTIC SYSTEMS ON RIEMANNIAN MANIFOLDS. It is of the utmost necessity for Australia to develop the theoretical expertise needed in the current era. The type of mathematics under investigation here is closely allied to that needed in much of the current boom in communication technology and medical research. The training which would be provided to the research associates is considerable, and would flow on to produce the expertise needed to keep the coming generation involved in modern technological development. I will maintain my active collaborative effort with leading mathematicians from the US, France and other countries, thus helping to keep Australia at the forefront of a significant field of research.Read moreRead less
Propagation of singularities for the Schrodinger equation. The time-dependent Schrodinger equation governs the evolution of quantum particles. In this project we aim to use new techniques from mathematical scattering theory to analyse solutions of the Schrodinger equation and obtain sharp bounds on their singularities. Controlling such singularities will allow us to deduce quantitative bounds on the number of eigenvalues in certain situations, and provide new techniques for studying nonlinear Sc ....Propagation of singularities for the Schrodinger equation. The time-dependent Schrodinger equation governs the evolution of quantum particles. In this project we aim to use new techniques from mathematical scattering theory to analyse solutions of the Schrodinger equation and obtain sharp bounds on their singularities. Controlling such singularities will allow us to deduce quantitative bounds on the number of eigenvalues in certain situations, and provide new techniques for studying nonlinear Schrodinger equations. Read moreRead less
Physics of Risk: new tools to survey the Australian market and beyond. The lives of most Australians depend on the dynamics of financial markets that affects investments, savings, business, employment, growth, wealth and -ultimately- the daily functioning of our society. Understanding, monitoring and managing the dynamics of financial markets is of crucial importance to policy-makers, financial institutions and businesses that are increasingly faced with managing risk, planning strategies and ta ....Physics of Risk: new tools to survey the Australian market and beyond. The lives of most Australians depend on the dynamics of financial markets that affects investments, savings, business, employment, growth, wealth and -ultimately- the daily functioning of our society. Understanding, monitoring and managing the dynamics of financial markets is of crucial importance to policy-makers, financial institutions and businesses that are increasingly faced with managing risk, planning strategies and taking decisions in an increasingly complex market-place. The project is also of importance to the continued evolution of physics in this country contributing to the emergence of a strong new area of statistical physics concerned with the ?real world? in a manner hitherto unknown.Read moreRead less
HARMONIC ANALYSIS, BOUNDARY VALUE PROBLEMS, AND MAXWELL'S EQUATIONS IN LIPSCHITZ DOMAINS. Boundary value problems for partial differential equations arise naturally when physical problems are expressed in mathematical terms. This project concerns the systematic development of the harmonic analysis of partial differential operators, and of the corresponding boundary integrals in order to solve such problems on irregular regions. Particular emphasis is given to studying the behaviour of electrom ....HARMONIC ANALYSIS, BOUNDARY VALUE PROBLEMS, AND MAXWELL'S EQUATIONS IN LIPSCHITZ DOMAINS. Boundary value problems for partial differential equations arise naturally when physical problems are expressed in mathematical terms. This project concerns the systematic development of the harmonic analysis of partial differential operators, and of the corresponding boundary integrals in order to solve such problems on irregular regions. Particular emphasis is given to studying the behaviour of electromagnetic waves both inside and outside irregularly shaped surfaces, and their propagation through it.Read moreRead less
Harmonic analysis of differential operators in Banach spaces. This proposal aims to develop harmonic analysis (the mathematical tools used in digital music and photography) in new contexts. It focuses on boundary value problems (the theory behind medical or geological imaging) and stochastic equations (which describe phenomena with random components such as the behaviour of financial markets).
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
Harmonic analysis in rough contexts. Harmonic analysis is a set of mathematical techniques aimed at decomposing complex signals into simple pieces in a way that is reminiscent of the decomposition of sounds into harmonics. It is highly efficient in analysing signals in homogeneous media such as wave propagation through the air that underpins wireless communication technology. However, wave propagation through inhomogeneous media, such as the human body in medical imaging or the Earth in geophysi ....Harmonic analysis in rough contexts. Harmonic analysis is a set of mathematical techniques aimed at decomposing complex signals into simple pieces in a way that is reminiscent of the decomposition of sounds into harmonics. It is highly efficient in analysing signals in homogeneous media such as wave propagation through the air that underpins wireless communication technology. However, wave propagation through inhomogeneous media, such as the human body in medical imaging or the Earth in geophysical imaging, is much harder to model. Phenomena with random components, as considered in finance for instance, are also problematic. This project is an important part of an intense international research effort to develop harmonic analysis in such rough contexts.Read moreRead less