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
Development Of Iron Complexes For The Treatment Of FriedreichÍs Ataxia & The Role Of Frataxin In Iron Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$616,143.00
Summary
Friedreich's ataxia (FA) is a neuro- & cardio-degenerative disease where there is an accumulation of toxic iron (Fe) in the mitochondrion. Work from our current NHMRC grant showed iron plays a significant role in FA pathology In fact, the CIs dissected the mechanisms of mitochondrial iron-loading & have published 8 papers in high impact journals with 3 papers in PNAS USA in the last 2 yrs Understanding of this process has led to the design of rationalised drugs for FA This work in this Renewal c ....Friedreich's ataxia (FA) is a neuro- & cardio-degenerative disease where there is an accumulation of toxic iron (Fe) in the mitochondrion. Work from our current NHMRC grant showed iron plays a significant role in FA pathology In fact, the CIs dissected the mechanisms of mitochondrial iron-loading & have published 8 papers in high impact journals with 3 papers in PNAS USA in the last 2 yrs Understanding of this process has led to the design of rationalised drugs for FA This work in this Renewal could lead to novel therapies for FARead moreRead less
Glycotherapeutics; A New Class Of Treatment For Alphavirus-induced Musculoskeletal Disease
Funder
National Health and Medical Research Council
Funding Amount
$449,868.00
Summary
The hallmark of alphavirus disease is crippling pain and joint arthritis, which often has an extended duration. Currently there is no licenced specific treatment for alphavirus disease and the increasing spread of infection highlights an urgent need for therapeutic intervention strategies. This grant looks at the potential of pentosan polysulfate as a promising drug-repurposing candidate for the treatment of alphavirus-induced arthritis.
Special Research Initiatives - Grant ID: SR1101002
Funder
Australian Research Council
Funding Amount
$21,000,000.00
Summary
Stem Cells Australia. Despite progress in stem cell research, scientists do not understand how stem cells “decide” what to become. Stem Cells Australia will draw upon strengths within Australia’s premier stem cell research universities and institutes. This collaboration between leading bioengineering, nanotechnology, stem cell and advanced molecular analysis experts, will fast-track efforts to deliver a fundamental understanding of the mechanisms of stem cell regulation and differentiation, and ....Stem Cells Australia. Despite progress in stem cell research, scientists do not understand how stem cells “decide” what to become. Stem Cells Australia will draw upon strengths within Australia’s premier stem cell research universities and institutes. This collaboration between leading bioengineering, nanotechnology, stem cell and advanced molecular analysis experts, will fast-track efforts to deliver a fundamental understanding of the mechanisms of stem cell regulation and differentiation, and the ability to control and influence this process. Stem Cells Australia will deliver new methods for stem cell propagation and manipulation, new translational technologies for therapeutic applications, and will prepare Australia’s future stem cell scientific leaders.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0667981
Funder
Australian Research Council
Funding Amount
$200,000.00
Summary
Kangaroo Genome Resource Management Facility. Increasingly, large Australian multicentre research programs in biological and medical sciences have a genomics component that involves integration of biological information with sequencing data. The success of these research programs depends on rapid internet access to the research information by all participating scientists. The universal design of the proposed information management system means that it can be easily adapted to support a broad ran ....Kangaroo Genome Resource Management Facility. Increasingly, large Australian multicentre research programs in biological and medical sciences have a genomics component that involves integration of biological information with sequencing data. The success of these research programs depends on rapid internet access to the research information by all participating scientists. The universal design of the proposed information management system means that it can be easily adapted to support a broad range of research programs. The development of this software program therefore has the potential to benefit research scientists, academics and students in many related fields, as well as the broader community, through enhancing research outcomes.Read moreRead less
New Insights Into Viral Inflammatory Disease Mechanisms And Approaches To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
This fellowship aims to establish how viruses cause disease, including how they evade the immune response to persist and cause disease for prolonged periods. My vision is that knowing how the virus and the immune system interact to determine disease severity will assist in devising new treatments and prevention programs to lessen the impact of viral diseases in Australia and worldwide.
ARC Centre of Excellence - Vision Science. This Centre will generate important new knowledge of the performance, logic and stability of vision and visual behaviour. This knowledge will help reduce the burden of vision impairment in Australia, increasing productivity, promoting healthy ageing and reducing the community costs of visual impairment (ca. $9.85 billion in 2004). The knowledge produced will also make possible world-class innovations in robotics, leading to novel automated vision system ....ARC Centre of Excellence - Vision Science. This Centre will generate important new knowledge of the performance, logic and stability of vision and visual behaviour. This knowledge will help reduce the burden of vision impairment in Australia, increasing productivity, promoting healthy ageing and reducing the community costs of visual impairment (ca. $9.85 billion in 2004). The knowledge produced will also make possible world-class innovations in robotics, leading to novel automated vision systems with applications in industry and national security. Other knowledge will develop novel diagnostic technologies, for application in health delivery.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989788
Funder
Australian Research Council
Funding Amount
$108,481.00
Summary
Nuclear Magnetic Resonance Microimaging and Relaxometry Facility. Many of the research projects to be supported by the facility are dedicated to improving our understanding of conditions and diseases that detrimentally affect many in our community. Projects investigating Alzheimer's disease, the central nervous system and its ability to repair, cancer and associated therapeutic treatments are some of the areas that will benefit from access to this equipment. The new facility will also provide un ....Nuclear Magnetic Resonance Microimaging and Relaxometry Facility. Many of the research projects to be supported by the facility are dedicated to improving our understanding of conditions and diseases that detrimentally affect many in our community. Projects investigating Alzheimer's disease, the central nervous system and its ability to repair, cancer and associated therapeutic treatments are some of the areas that will benefit from access to this equipment. The new facility will also provide unique insights into aspects of fundamental plant biology, with implications for improving crop productivity and better managing our natural ecosystems. The community will also benefit from the development and testing within the facility of new diagnostic tools and markers for a range of diseases.Read moreRead less
ARC Research Network for Enabling Human Communication. The Human Communication Network promotes interdisciplinary research in speech, language, and sound by and between humans and machines. The network connects leading and emerging researchers across disciplines, exploits previously unrecognised intersections, supports interdisciplinary graduate training and exchanges, provides database storage infrastructure, and consults with industry and government to set, not follow, research agendas. By ge ....ARC Research Network for Enabling Human Communication. The Human Communication Network promotes interdisciplinary research in speech, language, and sound by and between humans and machines. The network connects leading and emerging researchers across disciplines, exploits previously unrecognised intersections, supports interdisciplinary graduate training and exchanges, provides database storage infrastructure, and consults with industry and government to set, not follow, research agendas. By generating an explosion of new approaches and knowledge, the network will build Australia's reputation as a leader in communication science and technology via advances in automatic speech recognition, distress call monitoring, hearing prostheses, web interfaces, and data retrieval and data mining systems.Read moreRead less