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Immunobiology Of Carbohydrate Antigens In Xenotransplantation
Funder
National Health and Medical Research Council
Funding Amount
$563,554.00
Summary
Xenotransplantation, the transplanting of organs from other species, is now seen as a viable solution to the problem of lack of supply of suitable human donors. The recent production of genetically engineered pigs represented a critical step towards clinical xenotransplantation. However, other sugars still remain that cause rejection. This project examines the consequences of these sugars.
Does Galalpha(1,3)Gal Still Play A Role In Xenograft Destruction After The Production Of Gal Knockout Pigs?
Funder
National Health and Medical Research Council
Funding Amount
$706,062.00
Summary
Advances in surgical and immunosuppressive techniques has led to organ transplantation as the method of choice for the treatment of many diseases. However, the number of suitable donors is dwindling, due to many factors, but largely as a result of the reduction in deaths from car accidents. Xenotransplantation, the transplanting of organs from species other than humans, is now seen as a viable solution to the world wide problem of lack of supply of suitable human donors. The pig is the most suit ....Advances in surgical and immunosuppressive techniques has led to organ transplantation as the method of choice for the treatment of many diseases. However, the number of suitable donors is dwindling, due to many factors, but largely as a result of the reduction in deaths from car accidents. Xenotransplantation, the transplanting of organs from species other than humans, is now seen as a viable solution to the world wide problem of lack of supply of suitable human donors. The pig is the most suitable for a variety of reasons. However, the problem is that all humans contain natural antibodies to the pig which would lead to rejection within a few minutes as the antibodies bind to the transplant and reverse its rapid destruction (so called hyperacute rejection). Recent studies from our laboratory have indicated that most, if not all, of the antibodies react with the sugar - galactose present on many molecules on the surface of transplanted pig tissues. Our studies have indicated very large amounts of this material present in pig blood vessels - guaranteeing the early rejection of transplanted organs such as kidney, heart and liver. The production of knockout pigs which do not express the galactose sugar is an important pre-requisite for successful xenotransplantation. Recently knockout pigs which lack an enzyme that makes this sugar have been produced, but not all the sugar was destroyed. We have recently described a second novel enzyme that also makes this sugar. We will examine a role of this enzyme in xenotransplantation. These studies will be the prelude to the production of pigs which could be used for human transplantation.Read moreRead less
Organ transplantation is the measure of last resort for patients with organ failure. While this is a life-saving procedure, the long-term survival of transplant recipients depends on maintaining the new organ without rejecting it. The proposed research will create novel test systems that allow both patients and clinicians to monitor the concentration of the drugs required to suppress organ rejection. Such a test will reduce the cost of treatment and increase the long term survival of patients.
Kidney failure is a major health disorder in Australia and with more diabetes the number of patients waiting for transplant on dialysis is increasing. Current treatments give good initial survival of the kidney transplant but most kidneys are lost due to chronic damage . We propose a number of tolerance strategies in a model of kidney transplantation that will allow transplantation without longterm immunosuppression.
The Structural Basis For Recognition Of HLA-E By Both Innate And Adaptive Immune Systems.
Funder
National Health and Medical Research Council
Funding Amount
$206,255.00
Summary
Biochemistry and structural biology can be used to understand and visualize the three dimesional shape of molecules and the way they interact with other molecules. We will use these approaches to understand how various cells of the immune system recognise the protein HLA-E. This protein is normally present on the surface of healthy cells while it frequently retained inside both tumours and cells infected with viruses. This acts a signal for the immune system to kill these cells. However to avoid ....Biochemistry and structural biology can be used to understand and visualize the three dimesional shape of molecules and the way they interact with other molecules. We will use these approaches to understand how various cells of the immune system recognise the protein HLA-E. This protein is normally present on the surface of healthy cells while it frequently retained inside both tumours and cells infected with viruses. This acts a signal for the immune system to kill these cells. However to avoid being recognized by the immune system some viruses have developed ways to maintain HLA-E expression. This grant will attempt to understand exactly how the immune sytem recognizes HLA-E and how it discriminates between HLA-Eexpressed by healthy cells compared with HLA-E expressed by a virus-infected cell.Read moreRead less
Monitoring Of Leucocyte Cytokine-chemokines To Improve Morbidity And Rejection Rates In Lung Transplant Patients
Funder
National Health and Medical Research Council
Funding Amount
$373,973.00
Summary
Lung transplantation has become established therapy for many serious lung diseases. The early success rate is now very good, but at five years after transplant the survival rate is only around 60%. This problem is largely due to chronic graft failue as a result of chronic rejection or bronchiolitis obliterans syndrome. This project will specifically investigate the causes of BOS and thereby provide new information on how we may best treat this problem. An improvement in this area is critical.
HLA-E, a protein expressed by all cells regulates both innate and adaptive immune responses by binding to receptors found on white blood cells. This project will examine different ways that lymphocytes recognise this protein and its role in infection and transplantation.