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.
Epidermal Growth Control In Psoriasis And Normal Skin
Funder
National Health and Medical Research Council
Funding Amount
$451,980.00
Summary
Our skin protects us from damage, dehydration, infection and harmful UV radiation. At the same time, we expect it to remain healthy, smooth and looking good. How the skin, and more particularly its upper layer, the epidermis, adapts to all these requirements is a complex problem yet to be fully understood. This question forms the basis of our project proposal. The epidermis is a continuously self-renewing tissue, in which cells have an average life of 30 days before they are invisibly shed to th ....Our skin protects us from damage, dehydration, infection and harmful UV radiation. At the same time, we expect it to remain healthy, smooth and looking good. How the skin, and more particularly its upper layer, the epidermis, adapts to all these requirements is a complex problem yet to be fully understood. This question forms the basis of our project proposal. The epidermis is a continuously self-renewing tissue, in which cells have an average life of 30 days before they are invisibly shed to the outside. In normal states and when responding to injury or disease, this cell turnover speed can be finely tuned, for example accelerated in the case of a healing wound. In contrast, if damaged by the sun, epidermal cells undergo a form of cell suicide (apoptosis) to prevent tumours forming from cells with damaged genes. This changing turnover speed is controlled by a series of growth factors, or cytokines. Insulin-like growth factor-I (IGF-I) is a unique cytokine that can control both cell turnover rate, and cell death. We aim to uncover the complex biochemical interactions that allow the epidermal IGF-I system to achieve this seemingly contradictory task. This study is important because when the epidermis loses the ability to finely tune its turnover speed, ulcers, sun damage, the common skin disorder psoriasis, or worse still, skin tumours, arise. This project explores ways of manipulating the IGF-I system to prevent this, and builds on some technology developed by the research group that has already proven effective in the control of psoriasis. The project also promises to discover undiscovered growth regulators that could be used in new gene therapies for skin overgrowth diseases.Read moreRead less
Insulin-like Growth Factor Binding Protein-2 Is A Crucial Activator Of Aggressive Behaviour In Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$612,885.00
Summary
The insulin-like growth factor (IGF) system, required for normal development and adult life, is often altered in many diseases including cancer. Key regulators of the IGF system are the IGF binding protein (IGFBP) of which IGFBP-2 is the 2nd most abundant. IGFBP-2 may enhance or inhibit the IGFs, but the mechanisms are not clear. This proposal aims to dissect IGFBP-2 action with the ultimate goal to provide knowledge for the development of targeted therapeutic modulators of IGFBP-2 activity.
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.
Compared with normal-weight children, obese youth have a higher chance of developing diseases like Type 2 diabetes. With 1 in 4 Australian children now being overweight or obese, effective treatment programs need to be developed alongside those aimed at prevention. This program of research aims to identify which overweight/obese children are most likely to develop diabetes, with a particular focus on how infant nutrition regulates important growth factors to alter long-term diabetes risk.