The Effects Of Human Epilepsy Mutations On Synaptic GABA-A Receptors Studied By Localization-based Superresolution Microscopy
Funder
National Health and Medical Research Council
Funding Amount
$524,215.00
Summary
The genetic epilepsies are debilitating neurological disorders that are frequently associated with mutations in genes encoding neurotransmitter-gated receptors in the brain. The goal of this project is to understand mechanisms that cause changes in neuronal communication and lead to epilepsy on a single receptor level. This will lead to an improved understanding of the mechanisms of epileptogenesis and new insights into ways of treating different epilepsies.
The Role Of Force-sensing Ion Channels In Melanoma Migration
Funder
National Health and Medical Research Council
Funding Amount
$553,848.00
Summary
Metastasis of melanoma cells away from the primary tumour site carries a very poor patient prognosis.This research aims to characterise a novel signalling pathway that can regulate the migration (movement) of melanoma cells. This signalling pathway depends on force-sensing platforms that can rapidly convert physical inputs from the environment into an electrical signal within the cell. We are working to understand how these force-sensors function.
The cells that produce and maintain our cartilage, known as chondrocytes, do so by sensing changes in the mechanical environment, but precisely how chondrocytes detect these changes is not known. We are investigating the role of ion channels that are opened in direct response to mechanical movements within the cartilage.This project plans to identify the specific molecules that are participating in this process and to determine if they are therapeutic targets for treatment of osteoarthritis
How Does Sudden Cardiac Death Occur In Familial Hypertrophic Cardiomyopathy?
Funder
National Health and Medical Research Council
Funding Amount
$1,312,606.00
Summary
Familial hypertrophic cardiomyopathy is a leading cause of sudden cardiac death but the mechanisms for the induction of arrhythmia are unknown. This proposal has the potential to impact sudden death in the young and enable significant expansion of Australia’s research capacity into the treatment of familial hypertrophic heart disease in humans.
Nerve Excitability Assessment: A Novel Biomarker For The Early Detection Of Diabetic Neuropathy.
Funder
National Health and Medical Research Council
Funding Amount
$375,203.00
Summary
Australia has one of the highest rates of diabetes in the world. Diabetes may be complicated by the development of nerve damage, causing weakness and pain in the upper and lower limbs. The cause remains unclear and there are no tools available for its early detection. This study will provide further information about the cause of diabetic neuropathy and will investigate more sophisticated means for its early detection.
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.
Regulation Of RyR2 Channels By Calmodulin In Healthy And Diseased Hearts
Funder
National Health and Medical Research Council
Funding Amount
$614,421.00
Summary
In the heart, RyR2 is responsible for intracellular Ca2+ release. The RyR2 is comprised of a Ca2+ channel and accessory proteins such as CaM that regulate channel activity. Evidence suggests that RyR2 regulation by CaM is altered in heart failure and human arrhythmia syndromes, but there has been no direct evidence for this. We will provide this direct evidence plus determine how CaM regulates RyR2 channels and intracellular Ca2+ release and how this leads to cardiac arrhythmias.
Unravelling Mechanotransduction Pathways In The Heart
Funder
National Health and Medical Research Council
Funding Amount
$949,956.00
Summary
This project addresses the still unresolved question of involvement of mechanosensitive ion channels in heart hypertrophy and arrhythmias including ventricular arrhythmias. These pathological conditions are a cause of a broadening fiscal healthcare burden in Western societies. Consequently, investigating the role of this class of ion channels in heart disease presents a priority for medical science and a great opportunity to improve the health outcomes for the Australian people.
How Do Anaesthetics Work? A Rational Basis For Safer General Anaesthesia.
Funder
National Health and Medical Research Council
Funding Amount
$592,008.00
Summary
General anaesthetics are a mainstay of modern medicine, but have a small safety margin, requiring skilled anaesthetists for their safe use. There is growing evidence that general anaesthetic exposure may have long-term effects on brain function in both newborns and the elderly. This project will provide a detailed molecular description of anaesthetic action and specificity. It will provide the basis for designing new anaesthetics that are safer, both immediately and for long-term brain function.
The Awakening:GABA-A Receptors As Targets For Improving Motor Function
Funder
National Health and Medical Research Council
Funding Amount
$735,498.00
Summary
Zolpidem (Stilnox) is a “sleeping pill” that is reported "awaken" people with severe motor, memory and speech disabilities that result from stroke or other brain injury. We have identified a novel target by which zolpidem can exert these effects. This project will characterise this target and assess drug effects in models of stroke.