A Type II Diabetes Adn Obesity Prevention Program For Primary School Aged Rural Indigenous Children
Funder
National Health and Medical Research Council
Funding Amount
$1,497,369.00
Summary
This project aims to develop and evaluate the impact of an innovative multi-component community and school-based program for type II diabetes and obesity prevention program for Indigenous and non-Indigenous rural children.
Derivation Of Pancreatic Beta Cells From Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$2,968,050.00
Summary
People with type 1 diabetes require regular insulin injections because the organ that normally makes insulin, the pancreas, no longer functions. The goal of this program is to derive human fetal pancreas tissues from embryonic stem cells. Such tissue could be used to replace the missing insulin producing cells in people with type 1 diabetes. The program brings together expertise in ES cell biology at Monash University and the leading diabetes research at the Walter and Eliza Hall Institute.
Molecular Analysis Of Pathways In Diabetes (MAPDB) Study
Funder
National Health and Medical Research Council
Funding Amount
$3,348,000.00
Summary
The sequence of human genome provides a complete part-list of the genes and proteins that make our bodies. A most unknown subset of these parts work together in molecular pathways that underpin susceptibility and resistance to Type 1 diabetes and its complications. The MAPDB study will link patients, families, doctors, genome experts, immunologists, physiologists, statisticians and data base programmers together to illuminate these molecular pathways. In particular, the study will reveal genes a ....The sequence of human genome provides a complete part-list of the genes and proteins that make our bodies. A most unknown subset of these parts work together in molecular pathways that underpin susceptibility and resistance to Type 1 diabetes and its complications. The MAPDB study will link patients, families, doctors, genome experts, immunologists, physiologists, statisticians and data base programmers together to illuminate these molecular pathways. In particular, the study will reveal genes and pathways that medicate protection from diabetes and its complications - either by inhibiting T cell responses to pancreatic beta cells, protecting or regenerating beta cells in the face of metabolic or immunologic stress, or protecting eyes and kidneys from the damaging effects of high blood glucose. By identifying genes and proteins with these functions, the study will enable new treatments to be developed aimed at augmenting these protective pathways, to prevent diabetes starting in children at risk, and to preserve beta cell mass, protect transplanted stem cells or beta cells, and prevent eye and kidney damage in people already affected by Type 1 diabetes. Genes and proteins that are needed for T cell attack on beta cells will also be revealed. This information will enable new treatments to be developed that block these processes, to prevent diabetes from starting, to preserve beta cell mass and to prevent destruction of transplanted stem cells or beta cells. The MAPDB study will also identify different versions-alleles- of many of the genes in the pathways described above. Particular combinations of these gene alleles will be defines that can identify people at high risk of developing Type 1 diabetes, risk of cell or islet transplantation rejection, or at most risk for eye-kidney complications. Different gene combinations may be found that allow different kinds of Type 1 diabetes to distinguished. By creating ways to identify and distinguish people's individual risk, the study will yield diagnostic tests to enable new treatments and clinical trials to be targeted.Read moreRead less
Loss of insulin-producing beta cells leads to type 1 diabetes and rejection of allogeneic islet transplants. The aim of this program is to discover ways of protecting beta cells from damage. We will do this by investigating whether blocking crucial regulators of cell death can protect mouse and human beta cells from destruction in vitro and in vivo. In doing so, we aim to prevent diabetes in mice and potentially improve the survival of islet grafts after transplantation.
In type 1 diabetes the body becomes deficient in insulin production from pancreatic b cells because the immune system mistakenly attacks and destroys b cells as if they were an invading infection. Recurrence of autoimmune destruction of b cells also occurs following transplantation of whole pancreas or islet cells and may occur in the future when other engineered insulin producing cells are transplanted. The focus of this program is to better understand how b cells are killed by the immune syste ....In type 1 diabetes the body becomes deficient in insulin production from pancreatic b cells because the immune system mistakenly attacks and destroys b cells as if they were an invading infection. Recurrence of autoimmune destruction of b cells also occurs following transplantation of whole pancreas or islet cells and may occur in the future when other engineered insulin producing cells are transplanted. The focus of this program is to better understand how b cells are killed by the immune system and to test ways of protecting beta cells from these mechanisms. Because of the inaccessibility of the pancreas to study (particularly biopsy) in humans with diabetes, much of the proposed work will be carried out in b cells derived from non-obese diabetic (NOD) mice, the best available mouse model of type 1 diabetes. It is clear from the literature that a molecule called perforin found in cytoxic T lymphocytes (CTL) is a major, if not the major, mechanism the immune system uses against b cells. For this reason we will try to better understand the interaction between b cells and perforin and ultimately design ways of them from perforin-mediated cell death. It is equally clear that there are other mechanisms besides perforin that can cause b cell death and the program will also address discovery of these mechanisms and new ways to block them. Beta cells in NOD mice will be protected from perforin or other mechanisms by the addition of protective genes or removal of harmful genes using transgenic knockout technology. Addition or removal of genes involved in cell death can be done systematically and each protocol tested using NOD mouse model. The process of cell death that b cell undergo in type 1 diabetes is called apoptosis. Apoptosis is a general mechanism by which cells of all types die. Experts in the biology of apoptosis and perforin are important members of the program, providing the opportunity to translate the latest advances in cell death research to diabetes. This research addresses several of the specific research areas of interest to JDRF. It focuses on the prevention of b cell death in individuals with type 1 diabetes receiving islet transplants. It may be applicable in the future to protection of stem or precursor cells that have been differentiated into b cells or even to devising strategies to prevent the development of diabetes.Read moreRead less
Our work package looks at Control of pathogenic autoimmunity through regulation by the autoimmune regulator gene (AIRE) in thymic epithelial cells� and has a major influence on work package no 1). __ Design of specific tolerogenic peptide therapies based on the identification of tissue-restricted self-antigen epitopes escaping tolerance�, but interacts either directly or indirectly with all other packages
Novel Approaches To Pathogenesis, Diagnosis &treatment Of Autoimmune Diseases Based On New Insights Into Thymus-dependen
Funder
National Health and Medical Research Council
Funding Amount
$1,045,422.00
Summary
An individual relies upon their immune system to protect against invasion by hostile organisms. The system usually works well. Invading agents (the 'non-self') are detected and attacked by the immune system's patrolling killer T cells. These normally beneficial cells are called T cells because they were formed and educated in an organ called the thymus, which kick-starts our immune system in childhood, but falls into inactivity by adolescence. Sometimes the education system in the thymus goes wr ....An individual relies upon their immune system to protect against invasion by hostile organisms. The system usually works well. Invading agents (the 'non-self') are detected and attacked by the immune system's patrolling killer T cells. These normally beneficial cells are called T cells because they were formed and educated in an organ called the thymus, which kick-starts our immune system in childhood, but falls into inactivity by adolescence. Sometimes the education system in the thymus goes wrong and it releases T cells that mistakenly attack 'self' instead of 'non-self'. This causes autoimmune diseases, such as type1 diabetes, multiple sclerosis and rheumatoid arthritis. The Euro-Thymaide project aims to determine why and how self-attacking T cells are mistakenly released from the thymus into the body. Usually such errant T cells are detected and destroyed within the thymus, before they have the opportunity to escape and cause autoimmune diseases. The ultimate objective is to learn about the thymus recognition process and help the immune system detect and destroy faulty T cells that patrol the body, thereby preventing the onset of autoimmune diseases.Read moreRead less
Beta Cell Mass In Type 1 Diabetes Mellitus And Islet Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$3,070,136.00
Summary
This research program will examine the cellular and molecular mechanisms underlying the loss of Beta cell mass and function: During the pathogenesis of Type 1 Diabetes Mellitus (T1D); and Following islet transplantation. Though these processes have traditionally been considered to be purely immune-mediated, it is now clear that the response of the beta cell is critical to the final outcome of the auto-immune process and response to therapeutic interventions. Thus the complex interactions between ....This research program will examine the cellular and molecular mechanisms underlying the loss of Beta cell mass and function: During the pathogenesis of Type 1 Diabetes Mellitus (T1D); and Following islet transplantation. Though these processes have traditionally been considered to be purely immune-mediated, it is now clear that the response of the beta cell is critical to the final outcome of the auto-immune process and response to therapeutic interventions. Thus the complex interactions between the cellular and soluble constituents of the immune system, plus the effects of a deregulated metabolic milieu, are integrated at the beta cell. This in turn activates a series of complex transcriptional programs in the beta cell that together determine the beta cells ultimate functional status and survival. We will use knowledge gained from studying these processes to drive the development of novel therapeutic targets and strategies to improve the success of immune-based and transplantation-based therapies.Read moreRead less