How Does The P75 Neurotrophin Receptor Transmit Both Pro-survival And Pro-apoptotic Signals In Neurons?
Funder
National Health and Medical Research Council
Funding Amount
$265,500.00
Summary
Signaling by the two NGF receptors, TrkA and p75, determines the survival or death of sensory neurons and of certain brain neurons involved in memory and learning. The most baffling aspect of these receptors is that in most circumstances they cooperate with each other to maximise the survival of neurons when NGF is present, but in some situations they are opposed to each other. In the latter case, NGF treatment can lead to death, rather than rescue, of neurons. In the last three years we have de ....Signaling by the two NGF receptors, TrkA and p75, determines the survival or death of sensory neurons and of certain brain neurons involved in memory and learning. The most baffling aspect of these receptors is that in most circumstances they cooperate with each other to maximise the survival of neurons when NGF is present, but in some situations they are opposed to each other. In the latter case, NGF treatment can lead to death, rather than rescue, of neurons. In the last three years we have developed novel antisense oligonucleotides which can be used to switch off each receptor separately. These have been, and will continue to be, particularly valuable tools for our research. We have also uncovered a novel way in which the two receptors interact (via a signal transduction molecule known as SHC), which provides us with a competitive edge in this area. We have the expertise and equipment to identify and clone the missing factors that account for the paradoxical interactions between p75 and TrkA. A successful outcome from this project will have important benefits by improving our understanding of the factors controlling neuronal fate, and will help to develop treatments for neurodegenerative diseases.Read moreRead less
The amygdala is a part of the brain that processes and lays down emotional memories. Dysfunction in the amygdala is responsible for anxiety related disorders such post-traumatic stress disorder. I will study the neural circuits in the amygdala using innovative recordings and stimulation techniques. These studies will provide insight into the circuits that underpin anxiety related neurological disorders and provide targets for development of novel anxiolytic agents.
Investigating The Potential Of Human Stem Cells To Repair The Degenerating Auditory Nerve After Deafness
Funder
National Health and Medical Research Council
Funding Amount
$310,787.00
Summary
One in four Australians is predicted to experience some form of hearing loss by 2050. Hearing loss is irreversible and the chief clinical treatment available for severe to profound hearing loss is a cochlear implant. However, cochlear implant efficacy is limited by the degeneration of the auditory nerve following hearing loss. Using stem cells, this project will develop techniques to restore function to the auditory nerve through replacement of the specialised cells that comprise it.
Neurogenesis In The Amygdala And Hippocampus: A Role In Learnt Fear?
Funder
National Health and Medical Research Council
Funding Amount
$780,396.00
Summary
It has long been thought that neurons are only born once and then slowly die. Learning and memory formation is thought to occur by changes in the strength of connections between living neurons. However, the hippocampus is now known to produce new neurons throughout life. We have found that neurons are also born in the adult amygdala. In this project we will study how neurogenesis affects learning and memory formation that involve the hippocampus and amygdala.
Functional Maturation Of Adult Neural Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$701,390.00
Summary
This proposal seeks to understand how the production of functional nerve cells in the brain is regulated. Specifically we will focus on the way in which adult neuronal precursor cells (neuroblasts) in the brain acquire their functional characteristics as they mature into active entities capable of forming neural networks. We will examine the expression and activation of specific membrane proteins (ion channels) on the differentiation and migration of neuronal precursor cells.
Deciphering The Mechanisms Underlying LRP-mediated Axon Guidance
Funder
National Health and Medical Research Council
Funding Amount
$370,659.00
Summary
Nerve damage can develop post injury or disease and are often very debilitating, slow to heal and cause increased pain. Our work aims to examine a new class of molecules that we show can activate selected fat-receptors on nerve cells to guide the growth of regenerating nerves. We will determine how these receptors function with the aim of developing a novel class of therapeutics directed at healing nerve damage.
How Does Iron Accumulation Affect Parkinson’s Disease And What Controls It?
Funder
National Health and Medical Research Council
Funding Amount
$545,517.00
Summary
Currently there is no cure for Parkinson's disease, and although we have a number of treatments to manage the disease there is an urgent need for a further understanding of the disease process. This proposal will investigate the critical role that iron plays in the cause of neuronal cell death that results in Parkinson's disease, and will investigate methods for regulating metal levels in the brain.
Regulation Of Dendritic Ion Channels And Its Role In Intrinsic Neuronal Excitability In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$402,810.00
Summary
Nerve cells are able to regulate their activity to maintain the reliable transfer of information between cells. By conducting detailed electrical and chemical analysis of nerve cells this project will increase our understanding of how nerve cells regulate their activity, and provide important information on how this activity may be altered in brain disorders like epilepsy. The results of this research may also lead to the development of new more effective drugs to treat many brain disorders.
Neuronal Membranes And Connections In Dementia: Targets For Intervention
Funder
National Health and Medical Research Council
Funding Amount
$720,144.00
Summary
This research aims to understand why some people with Mild Cognitive Impairment (MCI) progress to dementia, whilst others do not. The fact that some people’s cognitive abilities can improve provides an opportunity to study the mechanisms that protect their brain cells from the degeneration associated with dementia. Understanding the cellular changes will lead to therapies that can be tested in the lab for individuals.
Creating Stem Cell Niches To Repair The Nigrostriatal System
Funder
National Health and Medical Research Council
Funding Amount
$837,033.00
Summary
It has been difficult to treat Parkinson's with stem cells because transplants make to few new cells and form tumors. In other organs, specialized locations called niches regulate the division and maturation of stem cells. By making a niche in the brains of animals with experimental parkinsonism we induced the brain to make new nerve cells and repair the parkinsonism. This is important because it shows how to use cell based therapies to treat neurodegenerative disorders. .