The Role Of Store-operated Calcium Entry In Neuronal Development
Funder
National Health and Medical Research Council
Funding Amount
$353,140.00
Summary
Defects in brain development can manifest in a range of disorders including autism and mental retardation. The highly complex, precise network that is our nervous system forms during development. Our work will determine the role of key proteins in guiding developing neurons. Understanding the function of such proteins will improve our ability to predict the outcome caused by mutations in these proteins, in the developing foetus.
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.
The Role Of TGFB1 In The Pathophysiology Of Late Stage Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$612,961.00
Summary
Schizophrenia is triggered in people with a genetic predisposition by as yet unknown environmental factors. Having shown that changes in gene expression in the brains of people with schizophrenia vary as the disease progresses, this application seeks to understand the changes in a pathway regulated by transforming growth factor ?1 that occur late in the progression of the illness. Understanding the changes in this important pathway could affect how people with schizophrenia are treated as their ....Schizophrenia is triggered in people with a genetic predisposition by as yet unknown environmental factors. Having shown that changes in gene expression in the brains of people with schizophrenia vary as the disease progresses, this application seeks to understand the changes in a pathway regulated by transforming growth factor ?1 that occur late in the progression of the illness. Understanding the changes in this important pathway could affect how people with schizophrenia are treated as their disorder progresses.Read moreRead less
Investigation Of The Role Of Nfix In Adult Neurogenesis
Funder
National Health and Medical Research Council
Funding Amount
$349,590.00
Summary
This project will identify key components of the molecular roadmap that mediates adult neurogenesis. Elucidating the genes involved in this process will represent a major advance in our understanding of how neurogenesis within the adult brain is orchestrated, and will provide molecular targets for practical applications aimed at harnessing adult neurogenesis for replacement therapies.
Nfib Regulates Glial Differentiation During Development And Disease Via Repression Of The Key Epigenetic Protein, Ezh2
Funder
National Health and Medical Research Council
Funding Amount
$572,912.00
Summary
Glial development is critical during development, and unrestrained proliferation of glial stem cells in the adult can lead to deadly brain cancers such as glioma. At present there is no cure for glioma and current treatments do not significantly delay tumour progression. Nfib is a transcription factor that may prevent tumour growth through cellular differentiation. We will investigate the role of Nfib during development and in the pathogenesis of glioma and its potential as a therapeutic target.
Role Of The Microglial Adaptor Molecule TYROBP In Alzheimer’s Disease Pathology
Funder
National Health and Medical Research Council
Funding Amount
$469,433.00
Summary
Immune activation characterizes Alzheimer’s disease (AD) brains; however, how it impacts AD progression is not understood. Our previous studies in AD brains identified the immune molecule TYROBP, pointing at both beneficial and detrimental effects triggered by this molecule. Here, we aim to understand in detail how TYROBP is involved in AD and how we can enhance its beneficial effects and decrease its unintended actions.
Molecular And Cellular Mechanisms Of Axon Guidance In The Vertebrate Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$330,735.00
Summary
There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can ....There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can be used to assist in trying to modulate and facilitate directed regrowth following injury.Read moreRead less
Regulation Of Neural Progenitor Cell Self-renewal By The RNA-binding Protein ZFP36L1 During Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$345,401.00
Summary
The timely differentiation of neural stem cells is critical during development, and the unrestrained proliferation of neural stem cells in the adult can lead to deadly brain cancers such as glioma. At present our understanding of the key molecules that regulate neural stem cell behaviour during these processes remains limited. In this proposal we will investigate the molecular determinants underpinning neural stem cell biology, both within the developing brain, and within glioma.
The research outlined in this application seeks to examine the role of calcium in the pathogenesis of AD. It will examine the hypothesis that the build-up of a protein known as the Abeta causes an increase in levels of calcium in nerve cells of the brain. This increase in calcium may trigger nerve cell damage and dementia. The ultimate aim of the research is to identify new targets for drug development in Alzheimer's disease.
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