Investigation Of The Molecular Basis Of Human Nevogenesis And Melanoma Initiation
Funder
National Health and Medical Research Council
Funding Amount
$598,220.00
Summary
The number of moles and lifetime exposure to solar UV are the major risk factors in melanoma development. A genetic association between the IRF4 gene and mole number and melanoma susceptibility has been reported. We propose that changes in the function of this gene will impact on the behaviour of melanocytes/melanoma cells, their response to UV radiation and interaction with surrounding cells. Understanding the function of this gene will provide crucial insight into the initiation of melanoma.
Interferon Mediated Control Of Legionella Infection
Funder
National Health and Medical Research Council
Funding Amount
$628,848.00
Summary
Bacterial lung infections are a serious cause of illness and death in humans. To fight infection the body activates the immune system using a network of signalling molecules. We are studying exactly how one of these signalling molecules called interferon controls the infection. Interferon induces the killing of bacteria that are replicating inside human lung cells. How interferon drives bacterial death is not known and this will be studied in this proposal.
Role Of IRF8 In Central Nervous System Glial Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$429,437.00
Summary
Glial cells of the brain change their function in response to local threats such as damage and this may contribute to either protection or injury of neurons. How glial cells mount this response is unknown. The goal of this project is to determine the role of the protein IRF8 in controlling the functional response of glial cells. The results will provide a better understanding of how glial cells contribute to neurological and neurodegenerative diseases.
Type I Interferon Signalling In Bacterial Infection
Funder
National Health and Medical Research Council
Funding Amount
$738,274.00
Summary
Infectious diseases are a leading cause of death in Australia. Activation of disease-fighting inflammasomes sets in motion rapid immune defenses against pathogens. In this project, we explore how cell-cell communication molecules known as type I interferons communicate with inflammasomes to achieve the best outcome in the body in response to deadly bacterial infection. Understanding how these signals communicate with one another could reveal new ways to fight infectious diseases.
Understanding Neuroinflammation In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,043,216.00
Summary
This project opens a new line of enquiry into the cellular signalling mechanisms involved in the progression of AD and establishes whether targeting the involvement of type-1 IFN signalling influences the evolution of AD. New and novel approaches are clearly required to treat AD. Importantly, we believe that neuroinflammation is common to all causes of dementia and targeting the neuroinflammatory pathways has much wider implications than targeting the primary causative pathway.
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.
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.
Modifying Brain Excitabilty By Upregulating The KCC2 Chloride Transporter
Funder
National Health and Medical Research Council
Funding Amount
$535,662.00
Summary
Brain activity depends upon the fine balance between neuronal excitation and inhibition. When this balance is lost, debilitating seizures can result, such as occurs in epilepsy. We have developed a new gene manipulation approach to enhance neuronal inhibition and prevent seizures in mice. We will examine the physiological mechanisms underlying this effect, and we propose that we can also use this genetic switch to stop the progression into epilepsy that occurs following a brain trauma.
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.