Over 2 million Australians have diabetes and up to one in three adults will develop diabetes or pre-diabetes in their lifetime with the associated burden of complications. It is not simply genetics, as the genetic variability cannot explain why some individuals and indeed some families appear to be programmed to have an inordinate burden of complications. Over the last decade we have developed state of the art technologies to characterise epigenetic changes in human clinical cohorts.
Preservation And Generation Of Beta Cells In Type 1 Diabetes With Novel Mimetic Peptides
Funder
National Health and Medical Research Council
Funding Amount
$1,096,055.00
Summary
Type 1 diabetes (T1D) is an autoimmune disease that destroys insulin producing beta cells in the pancreas. It can cause heart and kidney disease, and nerve damage. T1D is treated with insulin injections that can cause life-threatening low blood sugar levels. We have developed a new treatment that may stop beta cell loss, generate new beta cells and remove the need for insulin injections in T1D patients. A positive outcome will identify a completely new T1D treatment option.
A New Mechanism Of Tissue Fibrosis - A Small Peptide Regulator Of The TGF-beta1/Smad Pathway
Funder
National Health and Medical Research Council
Funding Amount
$768,757.00
Summary
Progressive scarring, or fibrosis, of organs leads to their loss of function. Fibrotic diseases are devastating to both the individual and our community and we lack effective therapies. We have identified a small protein, named SPRF, which represents a new mechanism in tissue fibrosis. These studies will examine the role of the SRPF protein in models of kidney, heart and lung fibrosis and its underlying mechanism of action. We will also test a therapy based on inhibiting SPRF function.
Tolerising Antigen-specific Immunotherapy For Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,395,549.00
Summary
We have developed a new immunotherapy to treat the underlying causes of type 1 diabetes (T1D) while leaving the rest of the immune system intact. To use this in patients, we need better tests to know when immune therapy is working. We will develop new methods to design the therapy and tools to track the relevant immune cells in T1D that work in variable patient groups. The knowledge gained will speed the pace of development and increase the chance of success of immunotherapy in T1D.
Mammalian Endotoxin: Characterisation Of Highly Inflammatory Endogenous Material
Funder
National Health and Medical Research Council
Funding Amount
$915,859.00
Summary
Inflammation drives development of many common diseases including heart disease, cancer, Alzheimer's disease and diabetes. We understand how bacterial molecules initiate inflammation during infections, but the nature of inflammatory stimuli that promote degenerative diseases of ageing has been elusive. In this project we will identify highly inflammatory molecules that have become altered in cells under stress. Knowledge of these pathways will promote new treatments for chronic diseases.
Casting The Net: A New Approach To Identify Therapeutics To Treat Type-2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,068,283.00
Summary
The discovery of treatments for type-2 diabetes (T2D) is a national health priority. In T2D, cells in the brain become 'insulin resistant' resulting in dangerously high blood sugar levels. There are no treatments for brain insulin resistance. The extracellular structures that surround brain cells undergo change in T2D, resulting in insulin resistance. By furthering understanding of these extracellular brain structures, this proposal will identify new drug targets to treat T2D.
Neuronal Regulation Of Systemic Mitochondrial Stress
Funder
National Health and Medical Research Council
Funding Amount
$865,605.00
Summary
Mitochondria are the powerhouses of cells. They generate energy from the food we eat and air we breathe. However, excess nutrients can cause mitochondrial stress and damage that lead to disease. The objective of this research is to understand how the brain regulates mitochondrial stress responses throughout the body. Therefore, this project will identify stress-response processes that are directly relevant to health and disease.
Examining The Metabolic And Cognitive Deficits Caused By Insulin Resistance In The Ventral Striatum
Funder
National Health and Medical Research Council
Funding Amount
$400,372.00
Summary
Brain insulin resistance is thought to cause metabolic and cognitive deficits, but the underlying neural mechanisms remain elusive. This project addresses this gap in our knowledge by examining how brain insulin resistance disrupts the metabolic regulation of food intake and the cognitive control of actions. The outcomes will provide new insights in disorders characterised by brain insulin resistance such as obesity and dementia.
Deadly Commute - Targeting The Trafficking Mechanisms That Licence Inflammatory Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$774,544.00
Summary
MLKL is a protein naturally found inside cells. MLKL is activated by inflammation. Once activated, MLKL relocates to the outer periphery of cells and kills them. Gut cells are especially vulnerable to death-by-MLKL and this problem causes Inflammatory Bowel Disease. Using cutting edge microscopy, we have discovered how MLKL moves to the periphery of cells prior to killing them. We will test if blocking this movement of MLKL to the cell periphery stops gut death and Inflammatory Bowel Disease.
Influenza A Viral Infection And Pregnancy Complications
Funder
National Health and Medical Research Council
Funding Amount
$1,346,858.00
Summary
Pregnant women who contract influenza are 5 times more likely to be hospitalised than the general population. Babies of mothers with influenza are also associated with increased perinatal mortality rates. We hypothesise that influenza infection in pregnancy significantly impairs the maternal vascular system resulting in maternal and foetal morbidity. Outcomes from this research may change current treatment modalities to improve maternal and foetal outcomes complicated by influenza infection.