The Role Of Corticothalamic Feedback On The Response Dynamics Of Thalamic Neurons
Funder
National Health and Medical Research Council
Funding Amount
$351,852.00
Summary
A fundamental question in neuroscience is how the brain selectively processes sensory information to generate a reliable representation of the world. Positioned in the centre of the brain, the thalamus plays a key role in sensory processing. This project investigates how the interaction between thalamus and cortex shapes the selection and gating of sensory information. This is a fundamental question in basic neuroscience with the potential to increase our knowledge about attentional deficits.
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100015
Funder
Australian Research Council
Funding Amount
$430,000.00
Summary
Australian Facility for Taphonomic Experimental Research . Australian facility for taphonomic experimental research: The aim of this project is to establish a unique Australian research facility dedicated to studying the physical, chemical, and biological processes of human decomposition. This facility will be the first of its kind in Australia and the Southern Hemisphere, drawing together a collaborative team of experts in a broad range of taphonomy disciplines. The results of the research are ....Australian Facility for Taphonomic Experimental Research . Australian facility for taphonomic experimental research: The aim of this project is to establish a unique Australian research facility dedicated to studying the physical, chemical, and biological processes of human decomposition. This facility will be the first of its kind in Australia and the Southern Hemisphere, drawing together a collaborative team of experts in a broad range of taphonomy disciplines. The results of the research are expected to advance our limited understanding of the taphonomic processes acting on remains in a natural Australian environment. The outcomes will assist police and forensic services to improve their procedures for searching, locating, recovering, and identifying missing persons, victims of homicide, and victims of disaster on both a national and international scale.Read moreRead less
Reducing flood loss - A data-assimilation framework for improving forecasting capability in sparsely gauged regions. Floods are the biggest and severest natural disaster we face year after year. Furthermore, there has been little improvement in our capability to prevent flood damage over past decades. This research proposes a paradigm shift in the way flood forecasting, warning and evacuation proceeds, using 21st century technologies for collecting and incorporating flood related data into exist ....Reducing flood loss - A data-assimilation framework for improving forecasting capability in sparsely gauged regions. Floods are the biggest and severest natural disaster we face year after year. Furthermore, there has been little improvement in our capability to prevent flood damage over past decades. This research proposes a paradigm shift in the way flood forecasting, warning and evacuation proceeds, using 21st century technologies for collecting and incorporating flood related data into existing modelling platforms. It is argued that assimilating real-time satellite soil moisture data into flood models can increase accuracy manifold, even if the images are uncertain. The understanding gained in course of the proposed project has the potential to significantly reduce the damage caused year after year, especially in the data poor regions of the world.Read moreRead less
Identifying and controlling the source of Campylobacter and Salmonella in Australia. This project will identify the source of foodborne illnesses due to Salmonella and Campylobacter in order to inform food regulatory policy. The ultimate aim is to reduce the amount of foodborne disease in Australia.