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.
I am a neuroscientist-biochemist-cell biologist determining the mechanisms by which lipids and lipid transporters regulate neurodegeneration and vascular disease. I have recently developed a prototype drug that shows promise as a novel therapeutic approach for Alzheimer's disease.
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.
The Regulation Of Apolipoprotein E Secretion By Human Macrophages
Funder
National Health and Medical Research Council
Funding Amount
$516,078.00
Summary
One of the major inflammatory cells in the body, the macrophage, is involved in a number of diseases, including coronary disease. ApoE is made and released by macrophages and appears to protect against the inflammation of coronary disease and may affect other conditions, including Alzheimer's disease. We have discovered pathways regulating the production and release of apoE by macrophages, and in this project will study these pathways in great detail. By controlling the production of this import ....One of the major inflammatory cells in the body, the macrophage, is involved in a number of diseases, including coronary disease. ApoE is made and released by macrophages and appears to protect against the inflammation of coronary disease and may affect other conditions, including Alzheimer's disease. We have discovered pathways regulating the production and release of apoE by macrophages, and in this project will study these pathways in great detail. By controlling the production of this important molecule we may reduce our risk of heart disease, and may be able to treat a range of inflammatory conditions which currently untreatable.Read moreRead less
Restoring Neuroprotective Sphingosine 1-phosphate Signalling In Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$857,656.00
Summary
Our research team has recently shown that a vital signalling lipid called S1P is lost from the brains of people who are in the early stages of developing Alzheimer's Disease. S1P protects brain cells against toxic insults that cause Alzheimer's Disease. This project will investigate how loss of S1P sensitizes people to the development of Alzheimer’s Disease, and the effectiveness of clinical drugs that restore S1P signals in protecting against Alzheimer’s Disease and restoring brain function.
Characterisation Of A Newly-discovered, Virulence-associated, Protein Secretion System Of Enteropathogenic E. Coli
Funder
National Health and Medical Research Council
Funding Amount
$582,149.00
Summary
The cell walls of bacteria act as a barrier to the export of any proteins they produce. We recently discovered a protein secretion system, which diarrhoea-causing strains of E. coli require to cause disease. The aim of this study is to characterise this secretory system, and discover how it functions and what it secretes. The knowledge obtained from this research will shed new light on how E. coli causes disease and could reveal novel methods to treat and prevent infections with this bacterium.