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.
Learning And Network Plasticity In A Primitive Sensory Cortex
Funder
National Health and Medical Research Council
Funding Amount
$461,557.00
Summary
Our brain is a uniquely powerful supercomputer, in part because it is ‘plastic’ -- that is, it can change itself when we adapt or learn something new. An understanding of the causes of brain plasticity is an essential part of any quest to understand the brain in sickness and in health. This research uses a laser microscope to ‘read the minds’ of mice as they learn about odours. By observing plasticity in action, we will gain deeper insights into normal brain function.
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.
Neural Basis Of The Functions Of The Primary Visual Cortex: Roles Of Feedforward And Intracortical Inputs
Funder
National Health and Medical Research Council
Funding Amount
$486,280.00
Summary
Signals from the eyes undergo extensive processing at the level of the primary visual cortex so that basic features in the scene such as lines, edges, colours and movement are coded in the activity of individual neurones. This project aims to further our understanding of this process at the basic cellular level. This will not only enable interventions that would help those with poor sight but also give us an insight into basic brain circuitry and its derangement in many neurological disorders.
Excitatory Interneurons: A Sensory Amplifier For Pathological Pain
Funder
National Health and Medical Research Council
Funding Amount
$649,848.00
Summary
Changes to the nervous system during pathological pain remain poorly understood. This poses a barrier to new and more effective pain therapies. We have recently shown that a population of excitatory nerve cells, which express a protein called calretinin, form an amplifier network within the spinal cord that enhances pain signalling. This application will determine how calretinin-positive nerve cells contribute to pathological pain and can subsequently be targeted to provide pain relief.
Decoding Dysfunctional Spinal Cord Circuitry In Chronic Pain.
Funder
National Health and Medical Research Council
Funding Amount
$516,101.00
Summary
Chronic pain is common, with one in five Australians having long-term pain that is serious enough to cause disability. Unfortunately this type of pain is difficult to treat, and current medicines are ineffective in many people, with unwanted side-effects. The aim of this project is to understand how signalling in the spinal cord changes following the development of chronic pain so we can find better strategies to reverse the symptoms and treat pain more effectively.
Mechanisms Underlying Efferent Feedback In The Vestibular System
Funder
National Health and Medical Research Council
Funding Amount
$491,475.00
Summary
The balance system has a remarkable, but poorly understood capacity for self-repair. An intrinsic feedback mechanism, the Efferent Vestibular System or EVS is thought to play a major role in this self-repair. Surprisingly, we know little about EVS function in animals or humans. We will study the EVS in mice and humans to gain a better understanding of how it works. This information will then drive the design of therapies that improve and restore balance in disease, injury, or ageing.
The Role Of TRPM2 Channels In Oxidative Stress-induced Liver Damage
Funder
National Health and Medical Research Council
Funding Amount
$576,265.00
Summary
Oxidative stress plays a central role in liver injury induced by drug toxicity, ischemia-reperfusion, non-alcoholic fatty liver disease and viral hepatitis. A hallmark feature of oxidative-stress mediated hepatocellular death is Ca2+ and Na+ overload which suggest activation of ion channels on the plasma membrane. This project will investigate the role of Transient Receptor Potential Melastatine 2 (TRPM2) non-selective channels in oxidative stress-induced hepatocellular death.
Using Artificial Synapses To Investigate The Functional Pathology Underlying Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$515,256.00
Summary
Epilepsy is a common neurological disorder. Some forms arise from hereditary mutations to GABA-A receptors. To advance our understanding of epileptogenesis, it is necessary to understand how mutations affect GABA-AR function. We will use a novel ‘artificial synapse’ system to characterise these mutant receptors. This will define how epilepsy is caused and inform us how to best tailor drug treatments for different epilepsy conditions.
Investigation Of Lipid-protein Interactions Of Mechanosensitive Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$409,785.00
Summary
Living organisms are imminently exposed to mechanical stimuli such as gravity, touch or sound. Sensing mechanical stimuli is therefore crucial for survival. One biological tool for sensing mechanical stress are the mechanosensitive ion channels that open in response to tension in cell membranes. We will study the interactions and coupling between membrane lipids and mechanosensitive ion channels. These interactions are essential for the function of these fascinating sensory biological molecules.