Neuroprotective Functions Of Autophagy Regulators In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$434,644.00
Summary
The accumulation of the beta amyloid protein has a central role in AD and enhancing its removal improves memory loss in animal AD models. This project builds on my recent finding of regulators of a cell housekeeping system, “autophagy” which accelerate removal of beta amyloid in cells. This study will advance knowledge into the protective functions of the autophagy regulators in reducing AD symptoms. Findings from this work might provide the basis for developing effective anti-AD therapeutics.
Alzheimer’s disease (AD), is the most common form of dementia, accounting for between 50-70% of all cases. There is general agreement that current treatments for AD/dementia are inadequate so new treatment strategies are desperately needed. I am addressing these challenges by developing new technologies to generate next generation treatments for AD.
The Role Of Copper In Ubiquitin-dependent Protein Degradation In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$588,622.00
Summary
Ubiquitin’s are small proteins that tag other proteins in a process known as “Ubiquitination”. Often this is to target them for degradation once they are no longer needed i.e. to take out the rubbish. This process is disrupted in Alzheimer’s disease (AD), which may contribute to the disease. This project aims to find out if copper, an essential metal for life, is required for this process. Drugs that are designed to deliver copper to brain cells have been effective in small AD clinical trials.
Disturbances Of DNA Regulation In Obesity, And Their Relationships To Metabolic Health
Funder
National Health and Medical Research Council
Funding Amount
$354,074.00
Summary
We have shown there exists significant differences in methylation patterns between Obese patients and healthy controls. In this study we will refine our understanding of the relationship between methylation and obesity. Our study will provide insight into how methylation changes observed in obesity influence downstream metabolic disorders such as diabetes and cardiovascular disease.
Uncovering The Function Of Susceptibility Variants In Alzheimer's Disease: From GWAS To Cell-Type Specific EQTLs And MQTLs
Funder
National Health and Medical Research Council
Funding Amount
$647,804.00
Summary
This project will investigate some of the genetic and epigenetic changes that occur inside certain brain cells that make them selectively vulnerable to Alzheimer's disease, in order to better understand the mechsnisms that give origin to the disease and identify possible targets for precision therapies.
Targeting G-quadruplex DNA As A Novel Therapeutic Strategy For Alzheimer’s And Frontotemporal Dementia
Funder
National Health and Medical Research Council
Funding Amount
$720,144.00
Summary
Dementia is the third leading cause of death in Australia and there is an urgent need to identify new ways of treating diseases that cause dementia. Our research is focused on targeting an unusual DNA structure in Alzheimer’s and Frontotemporal dementia (FTD). We will use a precision-targeted technology to better control formation of this DNA structure in disease-causing genes, allowing us to switch off the gene and hence stop disease progression for Alzheimer’s and FTD.
Investigating The Iron Proteome In Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$514,644.00
Summary
Iron is essential for brain function. When the delicate balance of metals in the brain is disturbed, neurodegenerative effects such as those seen in Alzheimer’s disease are observed. Although we know there is a link between iron and Alzheimer’s disease, we do not know which specific iron proteins are involved. This project will provide the first characterisation of different iron proteins in the brain to understand the mechanisms of disease and help in the search for new treatments.
How Do Mutations In Autophagy Receptors Cause FTD And ALS?
Funder
National Health and Medical Research Council
Funding Amount
$566,966.00
Summary
As cells age the "garbage disposal" process within cells slows down, becoming less functional. In inherited forms of dementia the genes involved often code for damaged proteins that "clog up" the disposal system or directly affect the “garbage men”. These defective garbage men genes include SQSTM1/p62, OPTN, VCP and UBQLN2. We will determine how these defective genes lead to build up of garbage in neuronal cells and how leads to disease.
Development Of Blood-based Biomarkers For The Early Detection Of Brain Amyloid And The Investigation Of The Natural History Of Alzheimer’s Disease.
Funder
National Health and Medical Research Council
Funding Amount
$720,144.00
Summary
To have a direct impact on the diagnosis and treatment of Alzheimer’s and other neurodegenerative diseases we need a detailed molecular understanding of the proteins that drive the disease. My laboratory develops and applies the most advanced analytical tools available to develop blood-based markers that can detect the development of Alzheimer’s disease before symptoms occur. This Fellowship will allow me to expand our understanding of the natural history of Alzheimer’s disease.
Establishing A Blood-based Biomarker Panel For Pre-clinical Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$716,778.00
Summary
The current gold standard biomarkers for Alzheimer’s disease (AD) are uneconomical and invasive, thus impeding early treatment prior to irreversible damage. I posit that biochemical changes associated with the disease are reflected in the blood several years prior to the clinical manifestation of the disease. Therefore, I propose to investigate these changes in individuals predisposed to AD, prior to the appearance of clinical symptoms, to identify biomarkers for the early diagnosis of AD.