In 2011 there were over 360 million people with type 1 and type 2 diabetes worldwide, who will require insulin treatment. There is an urgent need for insulin analogues that provide effective control of blood glucose to avoid unwanted hypoglycemic or hyperglycemic events. We have developed two novel insulin analogues with unique properties and aim to understand their mechanism of action. This knowledge will present new opportunities for improved insulin mimetics for diabetes treatment.
Understanding Ligand Binding Within The Insulin-like Growth Factor Family With Direct Application To Cancer Therapeutic Design
Funder
National Health and Medical Research Council
Funding Amount
$861,235.00
Summary
Cancer is a devastating disease and there is an imperative to develop new therapeutics. The so-called insulin-like growth factors are molecules that play a key role in the initiation and progression of cancer. Here we seek to understand how these molecules interact with cells and to develop drugs that might block their action.
Targeting The Insulin And Insulin-like Growth Factor Receptors In Cancer, Diabetes And Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$993,251.00
Summary
Diabetes, cancer and Alzheimer's disease are three major diseases facing Australia. This Project will investigate a common point-of-focus of these diseases, namely the interaction of insulin and the insulin-like growth factors with their receptor molecules on the cell surface. It will use recent breakthrough findings by the Chief Investigators to develop new therapeutic approaches for these diseases that could function by targeting these interactions.
Structural Events In Insulin And IGF Signalling - A Nanodisc Approach To A Problem In Cancer, Diabetes And Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$752,403.00
Summary
Insulin and its insulin-like growth factors play a major role in three major disease states facing ageing Australians—diabetes, cancer and Alzheimer's disease. We aim to understand how these proteins send messages into cells via their so-called receptors. We will isolate the receptor molecules from cells and then image them in an advanced electron microscope to produce three-dimensional images. Our findings will have implications for the design of therapeutics targeting the above three diseases.
Conformational Change In Insulin And Type I Insulin-like Growth Factor Receptor Upon Ligand Binding
Funder
National Health and Medical Research Council
Funding Amount
$415,365.00
Summary
Insulin and insulin-like growth factors bind to receptor molecules on the surfaces of cells. The binding event results in a signal being sent into the cell to initiate in the case of insulin, uptake of glucose into the cell and, in the case of the growth factors, normal human growth. Breakdown of these processes is implicated in a number of disease states, including diabetes, cancer and Alzheimer's disease. This Project aims to decipher the receptor triggering mechanism that is responsible for g ....Insulin and insulin-like growth factors bind to receptor molecules on the surfaces of cells. The binding event results in a signal being sent into the cell to initiate in the case of insulin, uptake of glucose into the cell and, in the case of the growth factors, normal human growth. Breakdown of these processes is implicated in a number of disease states, including diabetes, cancer and Alzheimer's disease. This Project aims to decipher the receptor triggering mechanism that is responsible for getting the signal into the cell.Read moreRead less
It’s The Amount That Counts: The Impact Of Seven Days Of Sleep Restriction On Predictors Of Type 2 Diabetes.
Funder
National Health and Medical Research Council
Funding Amount
$743,269.00
Summary
The aim of this project is to examine the relationship between sleep duration (5, 6, 7, 8, or 9h per day for one week) and glucose metabolism. This will allow us to quantify the amount of harm that different levels of sleep loss cause to the physiological systems that protect people from developing serious health disorders. In particular, the results of the project will be invaluable in the design of effective behavioural interventions for the prevention and/or treatment of type 2 diabetes.
A Novel Endogenous Inhibitor For The Treatment Of Diabetic Nephropathy
Funder
National Health and Medical Research Council
Funding Amount
$774,606.00
Summary
In various kidney diseases including the most common cause of end stage kidney disease, diabetic nephropathy, identifying the molecular mechanisms responsible for kidney failure are needed to assist in defining new targets and to develop more effective treatments. The proposed studies highlight the potential of a naturally occurring endogenous molecule called Lipoxin, as a modulator of kidney injury which may provide us with a novel approach to tackle the problem of diabetic nephropathy.
Therapeutic Targeting Of A New Growth Factor In Mesothelioma
Funder
National Health and Medical Research Council
Funding Amount
$317,775.00
Summary
Malignant mesothelioma is an aggressive and incurable cancer. This study will build on our recent data showing a protein termed FGF-9, not previously linked with mesothelioma, could significantly stimulate mesothelioma growth. This project will examine the biologic activities of FGF-9 and its receptors in mesothelioma, and the therapeutic benefits of antagonizing FGF-9 in mesothelioma in vivo.
Does Enhanced Vitamin D Activity In Bone Heal The Skeleton In Disorders Of FGF23 Excess?
Funder
National Health and Medical Research Council
Funding Amount
$855,925.00
Summary
X-linked hypophosphatemia (XLH) is a genetic disorder which results in phosphate wasting and rickets. This severe disorder has no effective treatment. We have compelling new evidence that the rickets in XLH is not primarily a disorder of low blood phosphate, but rather specific issue of low cellular levels and activity of vitamin D (1,25D) within bone. This proposal is designed to specifically demonstrate this new concept and outline a new paradigm for a new XLH treatment.
We have validated CDA1 as an effective target to retard kidney disease in diabetes using a mouse model where we deleted the CDA1gene. We have also developed a novel agent to inhibit CDA1 in order to retard diabetic kidney disease. In this application, we propose to confirm the efficacy of targeting CDA1 using various diabetes models and a range of strategies to target CDA1. We will also rigorously explore translation of these findings to a new treatment for diabetic renal disease.