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The aim of this application is to find new therapeutic strategies for genetic epilepsy. "Disease in a dish" models as well as whole animal models will be generated that contain patient gene mutations and the underlying disease processes will be characterised. Using these models a range of existing and new drugs will be tested to select those that most completely reverse these disease processes. These results will feed into clinical trials in patients with appropriate genetic profiles.
Epilepsy is a devastating disease with many patients poorly treated. We have identified a novel ion channel target in the brain that reduces seizure susceptibility. The aim of this proposal is to fully explore this target in a number of epilepsy mouse models using both pharmacology and molecular techniques.
Dysferlin And The Emergency Vesicle Fusion Of Membrane Repair
Funder
National Health and Medical Research Council
Funding Amount
$481,496.00
Summary
Membrane repair is a vital cell survival mechanism of all eukaryotic cells, using calcium-triggered vesicle fusion to ‘patch’ membrane ruptures. The muscular dystrophy protein dysferlin is a key mediator of membrane repair, although, exactly how dysferlin mends membranes has been unclear. We show that the calcium that floods through membrane tears, activates a group of enzymes called calpains, that specifically cleave dysferlin to release a specialist vesicle-fusion module for membrane repair.
Acute Stroke: Imaging The Ischaemic Penumbra With Perfusion CT
Funder
National Health and Medical Research Council
Funding Amount
$243,000.00
Summary
The burden of stroke is large. Clot-dissolving medication (thrombolysis) may dramatically improve the outcome of many patients with severe stroke by unblocking the affected brain artery. However, very few patients receive this medication, as the current approval is restricted to treatment within 3 hours of stroke onset. The major aim of thrombolysis is to rescue brain tissue with reduced blood flow (the ischaemic penumbra) from becoming irreversibly damaged (infarcted). The penumbra progressivel ....The burden of stroke is large. Clot-dissolving medication (thrombolysis) may dramatically improve the outcome of many patients with severe stroke by unblocking the affected brain artery. However, very few patients receive this medication, as the current approval is restricted to treatment within 3 hours of stroke onset. The major aim of thrombolysis is to rescue brain tissue with reduced blood flow (the ischaemic penumbra) from becoming irreversibly damaged (infarcted). The penumbra progressively becomes infarcted over the next 48 hours if blood flow is not restored by the blood clot in the brain artery being dissolved. Penumbral brain tissue cannot be identified with clinical assessment or standard CT scanning. New generation CT scanners are capable of assessing brain blood flow. Perfusion CT imaging (CTP) is well tolerated and time-efficient, and can be integrated into the brain CT scanning process performed on all stroke patients. Preliminary evidence suggests that CTP can distinguish between tissue that represents the ischaemic penumbra, and tissue that is already permanently injured. This project aims to validate the use of CTP in imaging the ischaemic penumbra. This will be based on testing the accuracy of CTP tissue signatures of the penumbra in predicting clinical outcome and final stroke size. This is the only national collaborative study planned worldwide for this relatively new but increasingly accessible imaging technique. The ability to rapidly identify under-perfused but still viable brain with CTP would add new and exciting management options to the routine emergency assessment of stroke patients. The results of this unique study could have a significant impact on the management of acute stroke worldwide. If validated, it is anticipated that CTP would be widely used to improve patient selection for stroke thrombolysis, especially in safely extending the time window so that a greater number of patients can be treated with better outcomes.Read moreRead less
Structural And Functional Networks In The Human Brain: Disturbance In Disease And Influence Of Genes.
Funder
National Health and Medical Research Council
Funding Amount
$568,892.00
Summary
Professor Graeme Jackson is a Neurologist at the Austin Hospital whose research is dedicated to the problem of understanding how epilepsy occurs and devising strategies for successful treatment. He is Deputy Director and head of the epilepsy division of the Florey Neuroscience Institutes which has research dedicated advanced MR imaging systems and physics support largely dedicated to solving these problems in epilepsy. He has 170 plus papers, 10 cited over 200 times. Career citations exceed 6000 ....Professor Graeme Jackson is a Neurologist at the Austin Hospital whose research is dedicated to the problem of understanding how epilepsy occurs and devising strategies for successful treatment. He is Deputy Director and head of the epilepsy division of the Florey Neuroscience Institutes which has research dedicated advanced MR imaging systems and physics support largely dedicated to solving these problems in epilepsy. He has 170 plus papers, 10 cited over 200 times. Career citations exceed 6000.Read moreRead less
Structural Connectomes In Traumatic Brain Injury: Can Secondary Disease Progression Be Stopped And Cognitive Deficits Be Reversed?
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Many people with traumatic brain injury (TBI) experience cognitive problems, including poor memory and concentration. TBI is often referred to as a ‘hidden disability’ because the overwhelming majority of patients with TBI show no abnormalities on standard MRI or CT scans. In my project, I will delineate the mechanisms of secondary injury in finer detail through enhanced neuroimaging techniques, resulting in new assessment and treatment modalities for individuals with TBI.
Mechanisms Of Ion Channel Dysfunction In Hereditary And Acquired Neuropathies
Funder
National Health and Medical Research Council
Funding Amount
$404,869.00
Summary
Nerve function is dependent on ion channels, which provide the basis for neurotransmission. Inherited or acquired abnormalities in ion channel function are important in diseases including epilepsy, pain disorders, neuromuscular diseases and toxic neuropathy. This project will use a combination of techniques to study mechanisms underlying nerve dysfunction to compare genetic nerve problems and acquired nerve damage to understand how damage occurs and develop new therapies and diagnostic tests.
Implementation Of Quality Use Of Advanced CT Imaging In Acute Stroke
Funder
National Health and Medical Research Council
Funding Amount
$1,128,594.00
Summary
Many centres now use advanced CT scanning techniques to assess stroke patient suitability for clot-dissolving treatment. However, there is major variation across Australia in the clinical application of advanced CT scanning techniques, which is a barrier to the delivery of this treatment. This project addresses the variation in CT imaging techniques by developing, piloting and evaluating the implementation of a standardised advanced CT scanning strategy for acute stroke patients.
Dysferlinopathy: A Genetic Disease Sheds Light On Membrane Repair For Muscle And Cardiac Injury
Funder
National Health and Medical Research Council
Funding Amount
$782,806.00
Summary
Muscles are damaged all of the time, as we stretch and contract them, but we don't fully understand how they repair themselves. We are studying the molecular steps taken by a muscle cell to repair membrane damage. Our research will provide valuable insights into how to treat muscular dystrophy and other conditions characterised by membrane damage to cells, such as heart attack and stroke.
Dysferlin Coordinates Membrane Repair For Skeletal And Cardiac Injury
Funder
National Health and Medical Research Council
Funding Amount
$459,270.00
Summary
Muscles are damaged all of the time, as we stretch and contract them, but we don't fully understand how they repair themselves. We are studying the molecular steps taken by a muscle cell to repair membrane damage. Our research will provide valuable insights into how to treat muscular dystrophy and other conditions characterised by membrane damage to cells, such as heart attack and stroke.