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A Novel Mechanism For Therapeutically Modulating Neurotransmitter-activated Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$667,529.00
Summary
This project aims to elucidate the mechanisms by which macrocyclic lactones bind to brain ion channel receptors. This will reveal fundamental new insights into the operation of these receptors and will have important implications for the design of novel treatments for a variety of central nervous system disorders.
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.
Oxytocin As A Novel Antagonist Of The Intoxicating And Addictive Effects Of Alcohol
Funder
National Health and Medical Research Council
Funding Amount
$739,106.00
Summary
Alcohol is Australia’s most harmful recreational drug and more effective treatments for alcohol abuse are desperately needed. The CIs have shown that administering oxytocin reduces alcohol intoxication and consumption, and prevents alcohol from acting at specific sites in the brain that are central to alcohol’s intoxicating and addictive effects. This project probes the effects of oxytocin at these sites and the potential utility of targeting this interaction to treat alcohol-use disorders.
The Contribution Of Subunit Interfaces To Receptor Activation In Ligand Gated Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$309,070.00
Summary
This project seeks to provide insights into new mechanisms that could be used to enhance or inhibit neuronal signalling. The family of pentameric neurotransmitter receptors that are key components in the process of neuronal signalling and are the target of this study. It will investigate the molecular motions that occur when the receptor shifts from the resting state to the activated state in the presence of neurotransmitter. This critical to understanding the normal function of these receptors ....This project seeks to provide insights into new mechanisms that could be used to enhance or inhibit neuronal signalling. The family of pentameric neurotransmitter receptors that are key components in the process of neuronal signalling and are the target of this study. It will investigate the molecular motions that occur when the receptor shifts from the resting state to the activated state in the presence of neurotransmitter. This critical to understanding the normal function of these receptors in the brain and how they can be modulated.Read moreRead less
Delta-containing GABA-A Receptors As Targets For Neuroprotection
Funder
National Health and Medical Research Council
Funding Amount
$953,825.00
Summary
After stroke, the neurotransmitter, GABA spills onto sites located away from the synapse. This spillover is hypothesised to have a protective role in limiting cell death. However the timeframe for this to occur is too long for observing significant beneficial effects after stroke. Therefore, stimulating this naturally occurring protective mechanism early using pharmaceutical interventions that target a specific type of GABAA receptor is an unexplored strategy to minimize cell death after stroke.
The Alpha5 GABA-A Receptor: Delineating An Emerging Therapeutic Target
Funder
National Health and Medical Research Council
Funding Amount
$481,178.00
Summary
GABA-A receptors mediate inhibitory synaptic transmission in the brain. Receptors containing ?5 subunits are therapeutic targets for many neurological disorders. We aim to characterise the functional properties of the main ?5-containing isoforms using high-resolution imaging and whole-cell recording. Our goal is to understand which ?5-containing isoform should be preferentially targeted (and how) when seeking to treat the various disorders in which these receptors have been implicated.
?4-containing GABA-A Receptors As Targets For ?-hydroxybutyric Acid (GHB)
Funder
National Health and Medical Research Council
Funding Amount
$610,572.00
Summary
?-Hydroxybutyric acid (GHB) is an elusive substance. On one hand, it is a prescribed drug to treat narcolepsy, and ameliorate alcohol withdrawal. On the other hand, GHB is the club drug “Fantasy” or “Liquid Ecstasy”, taken by many Australians for its social, sexual and euphoric effects. This proposal will identify GHB targets and provide insight to its mechanism of action.
Glycine Transport Inhibitors For The Treatment Of Pain
Funder
National Health and Medical Research Council
Funding Amount
$923,660.00
Summary
Chronic pain is particularly difficult to treat. Whilst currently used opioid drugs are effective in acute pain, they are either ineffective in chronic pain or have considerable side effects. In this project we will develop a new class of analgesics that have a different mechanism of action to traditional analgesics. It is hoped that these new drugs will provide long term pain relief without debilitating side effects.
Neuropathic pain is particularly difficult to treat and existing medications have considerable side effects. This project will develop a new set of glycine transport inhibitors that have the potential to provide pain relief without side effects.
Neuregulin 1 Type III Overexpression And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$651,966.00
Summary
Neuregulin (NRG1) is a neuronal growth factor and regulates the development of cortical inhibitory interneurons. Human studies suggest that NRG1 type III overexpression and deficient interneuron development underlie schizophrenia. Thus, we have developed a mouse overexpressing Nrg1 type III to discover mechanisms behind NRG1-related cortical pathology and schizophrenia-like behaviours and to clarify whether NRG1 type III interacts with environmental risk factors for the disorder.