The Persisting Vascular Effects Of Activation Of The Renin-Angiotensin System
Funder
National Health and Medical Research Council
Funding Amount
$628,456.00
Summary
Heart attacks and strokes are the major cause of death and disability in Australians. Heart disease is widely viewed to be the legacy of our diet and lifestyle, and even that of our parents. We propose to explore in detail the molecular mechanism of how this imprinting comes about and identify new targets to prevent, retard or reverse heart disease.
Modulating Pathogenic Signalling Towards The Prevention Of Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$622,655.00
Summary
Diabetes is associated with an increased risk of heart attacks and kidney failure. There remains an urgent need for new targets and therapies for preventing, arresting, treating and reversing these diabetic complications. My research directly focuses on identifying and validating these targets treatments, building on strong preliminary data and understanding of the molecular mechanisms set off by high sugar levels.
Interactions Between RAGE And The Type 1 Angiotensin Receptor Determine The Pro-atherosclerotic Actions Of Angiotensin II
Funder
National Health and Medical Research Council
Funding Amount
$521,956.00
Summary
Heart attacks and strokes are a major cause of death and disability in Australians. Activation of the renin angiotensin system plays a key role in the development and progression of atherosclerosis, the process that leads to narrowing and obstruction of arteries. In preliminary data we have found a way to block these pathways without affecting the control of blood pressure. We believe that interventions based on these data will be important for the prevention and treatment of heart disease.
RAGE And ACE2 Shedding As Therapeutic Targets In Diabetes And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$748,447.00
Summary
We have previously demonstrated the pivotal role of two shed proteins, Receptor for Advanced Glycation End-products (RAGE) and Angiotensin Converting Enzyme Receptor 2 (ACE2) in heart disease and diabetic complications. In this project, we will use a novel technologies to modify shedding of these proteins from the cell surface and alter their ability to cause disease.
Directed Molecular Evolution Of G Protein-coupled Receptors For Stable And Functional Expression In Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$383,479.00
Summary
Approximately half of all prescription drugs on the market act on G protein coupled receptors (GPCRs). The mechanisms underlying GPCR function are mainly unknown due to a lack of structural information. No solved structures exist for any of the estimated 800 human GPCRs, making it difficult to design new drugs. By applying advanced protein engineering techniques I aim to produce human GPCRs in bacteria to ultimately acquire structural information, which will enable novel drug development.
Assembly And Function Of Two Interacting Oncogenic Scaffolds
Funder
National Health and Medical Research Council
Funding Amount
$705,585.00
Summary
Aberrant signaling by the protein kinase superfamily is a known driving force for many cancers and inflammatory diseases. Recently, a subset of kinase-like proteins, termed pseudokinases, have emerged as crucial regulators of kinase signalling pathways. This proposal focuses on elucidating the scaffolding function and assembly of two pseudokinases, termed SgK223 and SgK269, which display oncogenic properties and aims to understand how their signalling abilities are subverted in a disease state.
Design And Engineering Of Adnectins For Diagnosis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$803,152.00
Summary
This project aims to engineer a naturally-occurring human protein, called an adnectin, to produce molecules that are able to bind specific targets in the human body, and as such may be used in the diagnosis and therapy of a range of diseases.
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.
Crosstalk Between The Repressive Histone Methyltransferases PRC2 And G9A: Structure-function Investigation To Open New Therapeutic Opportunities
Funder
National Health and Medical Research Council
Funding Amount
$595,205.00
Summary
The gene expression programs need to be precisely regulated and the misregulation of these programs can cause a broad range of human diseases. My research will focus on two protein complexes, which heavily contribute to the regulation of gene expression. My study will open a new path for developing new therapeutic strategies.
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.