Antigen-presenting cells control immune responses. Different types of these cells do different jobs and affect different diseases. We wish to control these processes by determining how the cells live and die. In particular we are interested in controlling the local immune responses during rejection of islet transplantation, which can cure type 1 diabetes.
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.
Functional Suicide Of Selected Dendritic Cells By Cytochrome C: An In Vivo Model Lacking Cross-presentation
Funder
National Health and Medical Research Council
Funding Amount
$597,476.00
Summary
Certain white blood cells (dendritic cells) activate the immune system, especially its T cells. Infection of such cells elicits killer T cell responses. However not all infections infect dendritic cells. In such cases, the infectious material is eaten by dendritic cells and moved to certain areas within the cell. This process is called cross-presentation and how important it is during various diseases remains moot. We now have a model of testing this by eliminating these cross-presenting cells.
Elucidating The Mechanism Of IL-2 Cytokine/antibody Mediated Transplantation Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
Organ transplantation is a life-saving treatment for end-stage organ failure. However, patients must take immunosuppressive drugs to prevent rejection, a lifetime of which increases the risk of infection and cancer. An alternative to drugs is to manipulate the immune system from within. We discovered a way to boost the immune ‘regulators’ so that they stifle the graft-destroying response. We are optimising this approach with the aim of transplanting organs without long-term immunosuppression.
The current treatment for diabetes involves diet, drugs and insulin treatment. While these are satisfactory for some adult onset diabetes, it is clear that in juvenile diabetes, the disease can progress in the presence of careful insulin dosage. It is apparent that the whole islet as a functional unit is likely to give the best control of diabetes, as when patients are transplanted with whole or segments of pancreas from human donors, as not only is there an improvement in their diabetic status, ....The current treatment for diabetes involves diet, drugs and insulin treatment. While these are satisfactory for some adult onset diabetes, it is clear that in juvenile diabetes, the disease can progress in the presence of careful insulin dosage. It is apparent that the whole islet as a functional unit is likely to give the best control of diabetes, as when patients are transplanted with whole or segments of pancreas from human donors, as not only is there an improvement in their diabetic status, the vessel lesions improve. Transplantation therefore offers a new therapy to diabetic patients for reversal of their disease and improvement in the serious side affects found in the eye, kidney and blood vessels. However, transplantation introduces a problem in that there is simply not sufficient human islets available for organ or islet transplantation, and in this light, animals are being examined as a possible source of islets. This is called xenografting or xenotransplantation. Of all the animal species, the pig is the most suitable donor for a variety of reasons, for example similar control of blood sugar to humans. The ultimate aims of the study are to examine possible genetic modifications that would allow the production of transgenic pig islets for transplantation to humans for the treatment of diabetes. The focus of the proposed studies is to elucidate the optimal combinations using mouse models. Importantly this study will establish the proof of principle and provide information on the genes that will be useful to finally genetically modify pigs for clinical use.Read moreRead less
Mechanisms Of Islet Graft Rejection And Acceptance
Funder
National Health and Medical Research Council
Funding Amount
$602,501.00
Summary
Islet grafts offer diabetic patients the promise of a return to insulin-independence. In this project we will study how natural regulatory T cells suppress islet graft rejection in a mouse model. We will determine where regulatory T cells interact with graft-rejecting T cells, and define the mechanisms used to mediate their suppressive effects. Our findings will aid in developing new ways to induce long-term acceptance of islet grafts without immunosuppressive drugs.
Expansion, Differentiation And Functional Analysis Of In Vitro Derived Pdx1+ Pancreatic Progenitors
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Type 1 diabetes is a condition that arises when the body's immune system destroys insulin-producing beta cells within the pancreas. Recent studies have shown that normal glucose control can be restored by replacing the missing beta cells by transplantation of cells from deceased donors. However, the demand for transplant material outweighs supply. The work described in this application seeks to define how insulin-producing beta cells can be derived in the laboratory from embryonic stem cells .