The Role Of Melanoma Tumour Antigen P97 (Melanotransferrin) In Melanoma Tumourigenesis.
Funder
National Health and Medical Research Council
Funding Amount
$563,242.00
Summary
The Role of Melanoma Tumour Antigen p97 (Melanotransferrin) in Melanoma Tumourigenesis Melanotransferrin (MTf) is a homologue of the iron transport protein, transferrin, and was one of the first well characterised melanoma tumour antigens. Our published studies have shown that MTf plays an important role in melanoma tumourigenesis in vivo. In this proposal, we will assess if it is associated with melanoma progression in patient samples and examine its role in melanoma growth and metastasis.
Investigating The Cellular Response To Iron-Depletion: The Trilogy Of ASK1, Thioredoxin And Ribonucleotide Reductase
Funder
National Health and Medical Research Council
Funding Amount
$552,572.00
Summary
Iron is crucial for many essential biological processes. Recently, we demonstrated that iron-depletion can affects important signalling pathways (e.g., JNK and p38) that play important roles in growth arrest and apoptosis. This study is designed to investigate the cellular and molecular effects of iron depletion which currently remains unclear. The research is crucial for understanding: (1) the effects of iron deficiency and (2) for understanding the effects of iron chelators that are used for t ....Iron is crucial for many essential biological processes. Recently, we demonstrated that iron-depletion can affects important signalling pathways (e.g., JNK and p38) that play important roles in growth arrest and apoptosis. This study is designed to investigate the cellular and molecular effects of iron depletion which currently remains unclear. The research is crucial for understanding: (1) the effects of iron deficiency and (2) for understanding the effects of iron chelators that are used for treating various diseases.Read moreRead less
Improving neuronal cell function with cell permeable copper complexes. Metal-based drugs offer an exciting new approach to treatment of neurodegeneration. However, little is known about how cells metabolise these drugs and this information is critical for further drug development. This project will determine how metal-based drugs are metabolised by neuronal cells and how this may result in therapeutic benefit.
Electrical properties of human dendrites. This project aims to determine the electrical properties of dendrites in human neurons. Dendrites are the primary site of synaptic input to neurons and their electrical properties play a key role in information processing in the brain. While we know much about the electrical properties of dendrites in other species, primarily rodents, little is known about the electrical properties of human dendrites. This project aims to address this gap in knowledge fo ....Electrical properties of human dendrites. This project aims to determine the electrical properties of dendrites in human neurons. Dendrites are the primary site of synaptic input to neurons and their electrical properties play a key role in information processing in the brain. While we know much about the electrical properties of dendrites in other species, primarily rodents, little is known about the electrical properties of human dendrites. This project aims to address this gap in knowledge for the first time. The results obtained will shed light on the mechanisms the brain uses to process information, and therefore will bring us a step closer to truly understanding ourselves.Read moreRead less
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
Tailoring cellulose properties by manipulating cellulose synthase. Cellulose, a highly abundant polymer produced by plants, has many existing uses in Australian fibre and polymer industries and potential uses as, for example, an abundant feedstuff for biomass conversion into ethanol and other high value products. The optimal properties for different applications vary so that, for example, high crystallinity cellulose gives strong fibres whereas low crystallinity cellulose dissolves in gentler so ....Tailoring cellulose properties by manipulating cellulose synthase. Cellulose, a highly abundant polymer produced by plants, has many existing uses in Australian fibre and polymer industries and potential uses as, for example, an abundant feedstuff for biomass conversion into ethanol and other high value products. The optimal properties for different applications vary so that, for example, high crystallinity cellulose gives strong fibres whereas low crystallinity cellulose dissolves in gentler solvents on the way to producing cellulose-based polymers. By exploring ways to adjust the properties of celluloses for use in different applications, we can deliver potential benefits to primary producers, industries and the environment.
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Role of the superior colliculus in sensory processing. The ability of an organism to attend to, and orient towards, stimuli in the environment is critical for survival. In the mammalian brain, the principal brain region performing this function is the superior colliculus. Despite its importance, little is known about the role the superior colliculus plays in sensory perception. This project addresses this issue by leveraging revolutionary new recording techniques to determine how the superior co ....Role of the superior colliculus in sensory processing. The ability of an organism to attend to, and orient towards, stimuli in the environment is critical for survival. In the mammalian brain, the principal brain region performing this function is the superior colliculus. Despite its importance, little is known about the role the superior colliculus plays in sensory perception. This project addresses this issue by leveraging revolutionary new recording techniques to determine how the superior colliculus codes sensory information and ultimately drives behaviour. The outcomes will be of immediate benefit to scientists studying sensory processing and perceptual decision making, and will help keep Australia at the forefront of brain-inspired engineering and the neuroscience-based knowledge economy.Read moreRead less
Coding of olfactory information in the piriform cortex. This project aims to understand how electrical activity in the primary olfactory (piriform) cortex enables mice to recognise and remember odours. By using optical recording techniques together with genetic tools, the project expects to generate new knowledge about how the mammalian brain builds internal representations of the external world. Specific outcomes of the project include new insights into the functional architecture of the pirifo ....Coding of olfactory information in the piriform cortex. This project aims to understand how electrical activity in the primary olfactory (piriform) cortex enables mice to recognise and remember odours. By using optical recording techniques together with genetic tools, the project expects to generate new knowledge about how the mammalian brain builds internal representations of the external world. Specific outcomes of the project include new insights into the functional architecture of the piriform cortex and fresh understanding of how olfactory information is encoded and stored in neural circuits. More broadly, the project aims to advance our understanding of how the brain works, with benefits for future improvements in artificial intelligence and brain-machine interfaces.Read moreRead less