Wnt-Ryk Signaling In The Establishment Of Major Axon Tracts In The Embryonic Mouse Brain
Funder
National Health and Medical Research Council
Funding Amount
$513,946.00
Summary
The corpus callosum is the major interhemispheric commissure in the human brain, comprising approximately 3 million myelinated fibers which connect homologous regions in the neocortex. To date more than 50 different human congenital syndromes have been described in which the corpus callosum does not form leading to epilepsy and mental retardation. We have identified a new guidance molecule (Ryk) which is crucial for corpus callosum formation. This project aims to dissect that molecular mechanism ....The corpus callosum is the major interhemispheric commissure in the human brain, comprising approximately 3 million myelinated fibers which connect homologous regions in the neocortex. To date more than 50 different human congenital syndromes have been described in which the corpus callosum does not form leading to epilepsy and mental retardation. We have identified a new guidance molecule (Ryk) which is crucial for corpus callosum formation. This project aims to dissect that molecular mechanisms controlling Ryk signaling during corpus callosum development. Our analysis of Ryk function will advance our understanding of the molecular mechanisms underlying the formation of this important commissure.Read moreRead less
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.
Developing Insight Into The Molecular Origins Of Familial And Sporadic Frontotemporal Dementia And Amyotrophic Lateral Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$6,377,279.00
Summary
There is strong evidence that frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) represent a spectrum of neurodegenerative disease with common origins. A combined study of FTD/ALS patient cohorts will provide greater power to identify these shared molecular origins. We aim to discover gene variants that cause, predispose, or modify onset and progression of inherited and sporadic FTD/ALS, and validate and study our discoveries in new cell and animal models of these disorders.
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.
Axon Degeneration And Axon Protection In CNS Disease And Injury
Funder
National Health and Medical Research Council
Funding Amount
$389,120.00
Summary
One of the major reasons for the clinical symptoms of neurological diseases such as Alzheimer’s disease and Motor Neuron Disease is the loss of connections between the nerve cells. Nerve cells are connected by specialized processes called axons. In disease these processes can breakdown. This project specifically looks at how axons break down in disease and tests therapeutic strategies to protect them.
A Central Role For ER-Golgi Trafficking In Motor Neuron Disease
Funder
National Health and Medical Research Council
Funding Amount
$434,652.00
Summary
Amyotrophic lateral sclerosis (ALS) patients currently face a bleak future. In the common global form of disease, the average length of survival after diagnosis is 31 months. Current therapies have at best a modest effect on the course of the disease with little or no benefit in terms of overall patient survival. This study will address the basic underlying biochemical mechanisms of disease in both sporadic and genetic forms of ALS. This studies will lead to opportunities to develop new therapie ....Amyotrophic lateral sclerosis (ALS) patients currently face a bleak future. In the common global form of disease, the average length of survival after diagnosis is 31 months. Current therapies have at best a modest effect on the course of the disease with little or no benefit in terms of overall patient survival. This study will address the basic underlying biochemical mechanisms of disease in both sporadic and genetic forms of ALS. This studies will lead to opportunities to develop new therapies in the future.Read moreRead less
Understanding The Role Of TDP-43 In Motor Neuron Disease.
Funder
National Health and Medical Research Council
Funding Amount
$654,091.00
Summary
Motor neuron disease (MND) is a fatal neurodegenerative disease with no cure. The cause of MND is poorly understood but new research has shown that defects in TDP-43, an RNA binding protein involved in gene regulation, can lead to the disease. This project is aimed at discovering the molecular mechanisms of TDP-43 function, which will improve the understanding of the disease and aid in the development of new therapies.
Elucidating The Mechanisms By Which Bis(thiosemicarbazone)-copper Complexes Protect Neurons In Models Of Neurodegenerative Diseases
Funder
National Health and Medical Research Council
Funding Amount
$353,377.00
Summary
Dr Liddell is a neuroscientist investigating potential therapeutic agents for the treatment of diseases of affecting the brain such as Alzheimer’s disease and Parkinson’s disease. He is examining a class of metal-based compounds that are showing strong potential for disease treatment, and is investigating how these compounds work. The findings will be used to further develop and improve these therapeutic agents, and may help understand the underlying causes of these diseases.
The Role Of Central And Peripheral Synaptic Activity In The Developmental Death Of Motoneurons.
Funder
National Health and Medical Research Council
Funding Amount
$463,145.00
Summary
Information processing in the nervous system relies on the effective communication between neurons and their target cells which make up our neuronal circuitry. At the centre of all this is the synapse, the specialized contact between a neuron and its target cell, be it another neuron in the brain or a target organ such as skeletal muscle. Our primary goal is to determine how the formation of synaptic connections during development regulates neuronal survival. In this proposal we have focussed on ....Information processing in the nervous system relies on the effective communication between neurons and their target cells which make up our neuronal circuitry. At the centre of all this is the synapse, the specialized contact between a neuron and its target cell, be it another neuron in the brain or a target organ such as skeletal muscle. Our primary goal is to determine how the formation of synaptic connections during development regulates neuronal survival. In this proposal we have focussed on the neuromotor system as it is a well characterised part of the nervous system. During development, 50% of motoneurons die at a time when they are making contact with skeletal muscle, and when contacts onto motoneurons by other neurons are being established. We believe that the formation of effective synaptic contacts onto motoneurons, as well as connections by motoneurons onto muscle are the key regulators of motoneuron survival. We are in a position to be able to address what regulates motoneuron death; as we have a number of mice which lack key molecules needed for the formation of specialisations that allow neuronal contacts to be made between motor neurons and their muscle, and with other neurons within the spinal cord. By examining the function of motoneurons, counting them and screening for molecular changes in these mice, we will be able to dissect out the mechanism of how a motoneurons' fate is determined during developmental motoneuron death. This research could help in developing strategies aimed at improving neuronal connections to improve neuronal viability. Our research will have important implications for our understanding about the basis of adult neuro-degenerative diseases, such as motor neuron disease and Alzheimer's, which are in part characterised by a molecular breakdown in neuronal connections that ultimately result in neuronal death.Read moreRead less