Reversal Of Diabetes In A Humanised Mouse Using A Clinically Applicable Vector System
Funder
National Health and Medical Research Council
Funding Amount
$842,173.00
Summary
Somatic gene therapy is one of the strategies that is being considered to cure Type I diabetes. Specifically, we wish to engineer liver cells to replace beta cell function. The aim of this project is to design a clinically-applicable protocol for the reversal of diabetes using a recombinant adeno-associated vector that delivers genes to human livers with high efficiency showing long term expression without pathogenicity and immunogenicity following a simple intra-peritoneal injection.
Defining Factors That Contribute To Individual Diversity In The Diet-health Axis
Funder
National Health and Medical Research Council
Funding Amount
$1,668,059.00
Summary
There is a complex interplay between nutrition and genetics such that one diet maybe good for some but not for others depending on genetic makeup. Preliminary experiments in flies and mice support this. We found that for some flies, diets high in fat are harmful resulting in short life but certain flies resist the harmful effects of fat and live a longer lives. We propose to unravel the gene-environment interaction and determine which genes might lead to optimal health outcomes on certain diets.
Reversing Autoimmune Diabetes By Controlling Pathogenic Effector T-cells
Funder
National Health and Medical Research Council
Funding Amount
$408,662.00
Summary
Type 1 diabetes (T1D) results from misdirected immune responses that destroy insulin-producing pancreatic cells. The ultimate goal of therapeutic strategies is to remove or inactivate the cells that attack insulin-producing cells, while leaving other cells, for example, those required for protection from infectious diseases and tumours, unaffected. Here we propose to test a new way of turning off the inappropriate immune reaction with the goal of preventing type 1 diabetes.
The amyloid beta (Ab) protein is implicated in Alzheimer’s Disease through its ability to impair brain metabolism. We have recently found that Ab can also impair metabolism in other tissues. This project will determine the role of Ab in regulating whole body metabolism and determine whether it is implicated in the development of metabolic diseases such as type 2 diabetes.
Conologues: Ultra-fast-acting Therapeutic Insulins Based On Cone Snail Venom Insulin Principles
Funder
National Health and Medical Research Council
Funding Amount
$1,082,866.00
Summary
The increasing prevalence of Type 1 and Type 2 diabetes demands better treatments. Our Project is based on a fascinating discovery by our international team of CIs of a new type of insulin within marine organisms that could form the basis of a novel diabetes therapeutic. Within our Project we will exploit this discovery to develop a new class of ultra-rapid-acting therapeutic insulins.
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.
Metabolic Wiring In Adipocytes - Unique Role In Maintaining Long-term Health
Funder
National Health and Medical Research Council
Funding Amount
$1,077,886.00
Summary
Fat cell metabolism is wired to optimize the cell’s ability to make and store lipid while programming the cell to fulfil its function in whole body metabolism. We will: 1) map fat cell metabolism under optimal and insulin resistant conditions; 2) explore the role of 3 nodes in his metabolic circuit predicted as control points; 3) use a novel genetically engineered mouse model to explore the functional significance of fat cell metabolism in whole body insulin sensitivity.
Elucidation Of The Mechanism Of IL-22-Mediated Suppression Of Β-Cell Stress In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$222,322.00
Summary
Pancreatic ?-cells produce the hormone insulin that controls blood sugar. Type 2 diabetes is characterized by inability of stressed ?-cells to make sufficient insulin to control blood sugar. We discovered that an immune factor, IL-22, protects ?-cells from stress. Treatment of diabetic mice with IL-22 resolves all the major problems in diabetes. This project seeks to reveal the mechanisms by which IL-22 protects ?-cells from stress, with potential for development of novel diabetes therapies.
Dissecting The Role Of Selective Insulin Resistance In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$980,624.00
Summary
Insulin resistance is a clinical condition where insulin, secreted from the pancreas in response to meals, is unable to fulfill its normal function. It is intimately linked to obesity and associated diseases - type 2 diabetes, cancer and cardiovascular disease. This proposal examines mechanisms contributing to insulin resistance and how insulin resistance leads to disease. We will identify drug targets with improved specificity and lead to novel insight into the risks of current treatments.
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.