Context Is Everything – Understanding How Spatial, Temporal And Behavioural Context Affect Sensory Processing
Funder
National Health and Medical Research Council
Funding Amount
$512,382.00
Summary
A possum in a tree is cute to see on a bushwalk, but scary to hear when we are trying to sleep. This illustrates that how we perceive a “target” is affected by “modulators” that are close in space or time to the target, or by the task at hand. Deficits in contextual modulation are apparent in many neurological conditions. This project will investigate the neural circuitry that mediates spatial, temporal and task-related contextual modulation.
What drives the pain associated with inflammation is unknown as is the relationship between pain and the extent of tissue damage associated with disease, for example, arthritis. Our laboratory has shown that a particular protein is a key mediator of inflammatory pain. The project is to understand how this particular protein promotes pain, including how it sensitzes neurons.
Role Of Calcium-activated Potassium Channels In Neuronal Excitability, Synaptic Plasticity And Sensory Processing
Funder
National Health and Medical Research Council
Funding Amount
$612,272.00
Summary
Disturbances in brain function, as occur in diseases such as epilepsy and schizophrenia, are associated with abnormal electrical activity. This electrical activity leads to increases in calcium inside nerve cells. In this project we plan to investigate how changes in calcium inside nerve cells regulates electrical activity, and how this impacts on the capacity of the brain to process and learn new information.
Characterisation Of The Molecular Mechanisms Of Abeta-induced Proteolysis Of The Neural Cell Adhesion Molecule 2 (NCAM2)
Funder
National Health and Medical Research Council
Funding Amount
$374,666.00
Summary
Neurons in the brain are connected by synaptic contacts. Amyloid beta peptide accumulating in the brain in Alzheimer’s disease destroys synaptic contacts by degrading synaptic cell adhesion molecules which maintain the structure of the contacts. The aim of the project is to characterise the molecular mechanisms of amyloid beta-dependent degradation of synaptic cell adhesion molecules. The project will identify strategies that can be used to inhibit synapse loss in Alzheimer’s disease.
Microglia As Primary Drivers Of Stress-induced Changes In Neuronal Connectivity
Funder
National Health and Medical Research Council
Funding Amount
$475,781.00
Summary
Persistent exposure to stressful events can produce serious and lasting disturbances in cognitive function. Our research group has recently identified that microglia may play a very significant role in these disturbances. The studies to be undertaken in this proposal will provide fundamental knowledge on how microglia contribute to neuronal plasticity, and how microglia via their effects on neurons regulate complex cognitive behaviour.
Neuronal Toll-like 2 Receptors Contribute To The Spread Of Parkinson's Disease
Funder
National Health and Medical Research Council
Funding Amount
$900,010.00
Summary
How the pathological protein in Parkinson’s disease (PD), ?-synuclein, spreads through the brain remains unknown. Toll-like receptor 2 (TLR2) located on microglial cells have been identified as the receptor responsible for the internalization of ?-synuclein by this cell. We have found TLR2 in PD neurons accumulating Lewy pathologies, suggesting that neuronal TLR2 contributes to the neuronal spread of ?-synuclein in PD, a theory requiring further biological evidence prior to therapeutic targeting
The Role Of LIM Domain Kinase 1 In The Pathogenesis Of Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$565,531.00
Summary
Alzheimer’s disease is characterized by progressive loss of cognition. Few Australians have remained untouched by the effects of Alzheimer’s disease in their families or social circles. Unfortunately, there is no cure and current therapies are limited to modest symptomatic relief. This project will explore the role of a protein that regulates the structural integrity of brain cells in disease, and test if targeting this protein could prevent disease progression.
Microglial Paralysis In Post-stroke Neurodegeneration: Help Or Hindrance?
Funder
National Health and Medical Research Council
Funding Amount
$512,351.00
Summary
Dementia and cognitive decline may occur months or years after a stroke, associated with delayed loss of brain cells in different brain regions. We recently discovered that the cells responsible for protection and repair of brain, called microglia, become paralysed in these regions. We will use a live-imaging microscope to determine whether the microglial paralysis causes brain cell death. We will also determine if a commonly used stroke prevention drug can worsen the microglial paralysis.
Abnormalities in cells at the back of the eye called photoreceptors are associated with at least 50% of all cases of blindness in this country.This project will examine a novel mechanism of photoreceptor death. In particular, whether abnormalties in support cells at the back of the eye cause photoreceptors to lose contact with their nutrient source and die.