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
Lysosomal Dysfunction As An Inhibitor Of Vitamin B12 Utilisation In Neurodegenerative Diseases
Funder
National Health and Medical Research Council
Funding Amount
$554,901.00
Summary
Vitamin B12 is required for red blood cell formation, DNA synthesis and normal neurological function. B12 deficiency contributes to age-related cognitive decline and Alzheimer’s disease. This research will provide important new information regarding the ageing process and the impact that brain changes associated with ageing and Alzheimer's disease have on B12 metabolism. It will provide important information related to the therapeutic potential of B12.
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.
Defining The Mechanisms By Which ABCA7 And ApoE Control Alzheimer's Disease Risk. Functional Characterisation Of New Therapeutic Targets For Dementia Prevention And Treatment.
Funder
National Health and Medical Research Council
Funding Amount
$687,975.00
Summary
Alzheimer’s disease (AD) is the major cause of dementia and is currently without a curative treatment. An understanding of the pathways that lead to AD is urgently required to develop approaches for treatments. We have discovered new pathways by which proteins called ApoE and ABCA7 control AD. We now aim to define precisely how these proteins work in the brain and use this information to develop therapeutic approaches to treat AD in humans.
Isoform-dependent ApoE Processing By Human Induced Pluripotent Stem Cells. A Novel Pathway Linking APOE Genotype And Alzheimer’s Disease Risk.
Funder
National Health and Medical Research Council
Funding Amount
$429,495.00
Summary
We recently discovered that a protein called apoE is cleaved in the brain to generate a small fragment that may have neuroprotective properties. We also discovered that human induced pluripotent stem cell (iPSC)-derived neurons produce apoE fragments identical to those in the brain. We will now characterise iPSC apoE and assess its neuroprotective properties. This will resolve the basis for the association of apoE with AD risk and potentially provide a new target for AD treatment.
Targeting Post-synaptic Tau To Treat Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,686,311.00
Summary
We have previously identified post-synaptic tau as being critical in mediating toxicity in Alzheimer's disease brains. This project aims at understanding the exact underlying molecular mechanisms and, more importantly, developing novel drugs to block early toxicity that initiates cascades that eventually lead to brain atrophy and dementia. To achieve this aim, this project will generate and utilize models of Alzheimer's disease in combination with a broad range of latest analytical tools.
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.
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.