Trace Element Regulation In Neurological Disease: From Molecular Pathogenesis To Translational Impact.
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Neurodegenerative diseases such as dementia and motor neuron disease are a major health burden for Australia and new approaches to treatment are urgently required. Essential trace elements such as copper, zinc and iron show major changes in neurodegneration, however, we do not understand how this drives disease processes. This proposal will develop an innovative 3D ‘brain on a chip’ cell model to probe the role of trace elements in brain pathology and identify exciting new treatments options.
Functional Copper Deficiency Models Of Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$454,691.00
Summary
Alzheimer's disease is a serious neurodegenerative disease which increases in incidence with age. It affects the quality of life and care required for approximately 160,000 Australians and costs the national economy 6.6 billion dollars per annum. Current therapy is of limited efficacy. Our studies are directed towards testing the hypothesis that a functional deficiency of the essential trace element, copper, occurs in the brain with ageing, and this leads to oxidative stress and death of neurons ....Alzheimer's disease is a serious neurodegenerative disease which increases in incidence with age. It affects the quality of life and care required for approximately 160,000 Australians and costs the national economy 6.6 billion dollars per annum. Current therapy is of limited efficacy. Our studies are directed towards testing the hypothesis that a functional deficiency of the essential trace element, copper, occurs in the brain with ageing, and this leads to oxidative stress and death of neurons associated with Alzheimer's disease. We will use animal and cell culture models to test this hypothesis which is based on promising preliminary data from such models. We believe that beta amyloid, which accumulates in Alzheimer's brains and is believed to be a major part of the pathological mechanism, has a normal role in maintaining copper balance and that this balance is disturbed by ageing or particular mutations. This research should lead to better treatments using drugs which mobilise copper entry into cells.Read moreRead less
Studies On Mechanisms Of Vesicular Trafficking And Catalysis For The Menkes (MNK) Copper-transporting P-type ATPase
Funder
National Health and Medical Research Council
Funding Amount
$363,757.00
Summary
Copper is an essential trace element for all organisms. Copper is needed for many processes including energy metabolism, the making and maintenance of strong bones and arteries with sufficient elasticity, the synthesis of chemical transmitters in the brain and for the reactions which remove toxic Ofree radicalsO. Copper is also used by the proteins involved in important neurological diseases including Alzheimers disease and Omad cowO disease. Menkes disease is an inherited and usually lethal cop ....Copper is an essential trace element for all organisms. Copper is needed for many processes including energy metabolism, the making and maintenance of strong bones and arteries with sufficient elasticity, the synthesis of chemical transmitters in the brain and for the reactions which remove toxic Ofree radicalsO. Copper is also used by the proteins involved in important neurological diseases including Alzheimers disease and Omad cowO disease. Menkes disease is an inherited and usually lethal copper deficiency disorder in humans, and the diverse and detrimental symptoms of this disease related to organs and tissues described above is a stark indicator of the essentiality of copper. We have carried out extensive research on Menkes disease and in particular the Menkes protein which in normal individuals plays a major role in maintaining the copper balance in cells, i.e. enough Cu to satisfy nutritional needs of cells but not too much which causes toxicity. The normal Menkes protein catalyses the transport of Cu across membranes of cells to the areas where it is needed by copper-dependent enzymes which themselves catalyse important chemical reactions. The normal Menkes protein functions as a molecular pump. We have discovered that this protein can OsenseO Cu concentrations in the cell and when these reach potentially toxic levels it can move (traffick) via small vesicles to the plasma membrane which surrounds cells. There it pumps the excess Cu out of the cell and returns to its original location. Our studies are directed to understanding the molecular mechanisms which permit this remarkable protein to achieve a copper balance in living cells. The findings will be of major significance in understanding and treating acquired and inherited diseases involving copper deficiency or copper toxicity.Read moreRead less
Validation Of Non-invasive Finite Element Method Based Localization Of Seizure Onset Zone In Epilepsy Using EEG-MEG
Funder
National Health and Medical Research Council
Funding Amount
$87,191.00
Summary
Epileptic seizures in the brain are often focal. If anti-epileptic drugs are ineffective, a deep brain stimulator may be implanted to abort seizures at their onset or the seizure tissue may be removed. This project aims to locate the seizure tissue from non-invasive EEG-MEG recordings of seizure-like brain activity using a realistic computer model of the electromagnetic fields in the brain. Knowing the location more exactly will improve the outcomes of deep brain stimulation and removal surgery.
Development And Validation Of A Finite Element Model For Orthopaedic Screw Insertion Into Trabecular Bone
Funder
National Health and Medical Research Council
Funding Amount
$420,454.00
Summary
Osteoporosis is a disease of the bones that results in reduced bone strength and susceptibility to fragility fractures. Due to the spongy nature of osteoporotic bone, surgeons face major difficulties in obtaining secure fixation of bone screws. Our aim is to develop and validate a computer model of orthopaedic screw insertion into trabecular bone based on micro-computed tomography image data. This will allow an assessment of the most appropriate screw designs for stable fixation of implants.