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The Regulation Of Monocyte Derived Dendritic Cells (moDCs) During Allograft Rejection
Funder
National Health and Medical Research Council
Funding Amount
$110,218.00
Summary
Islet transplantation can cure type 1 diabetes, but the required drugs for immunosuppressing graft rejection have side effects. Therefore understanding how immune rejection occurs so that we can suppress in a more discreet selective way is our goal. A type of cell that is prominent during graft rejection is the monocyte derived dendritic cell. We propose that this cell is critical for orchestrating immune responses during rejection. Therefore we wish to determine how such cells are controlled.
Investigation Into The Role Of Regulatory B Cells In Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$400,385.00
Summary
Solid organ transplantation is the most effective therapy for treating organ failure and some cancer. However, a common complication that occurs is graft rejection. The current aim is to develop procedures that reduce the risk of graft rejection without the use of immunosuppressive drugs, which can be toxic and make recipients more susceptible to infection. We are investigating the ability of a cell that is part of the immune system to down-regulate over-reactive immune responses and therefore r ....Solid organ transplantation is the most effective therapy for treating organ failure and some cancer. However, a common complication that occurs is graft rejection. The current aim is to develop procedures that reduce the risk of graft rejection without the use of immunosuppressive drugs, which can be toxic and make recipients more susceptible to infection. We are investigating the ability of a cell that is part of the immune system to down-regulate over-reactive immune responses and therefore reduce rejection.Read moreRead less
The Role Of Th17 And Tregs In The Development Of Tolerance And Rejection In A Murine Model Of Renal Allograft Rejection
Funder
National Health and Medical Research Council
Funding Amount
$110,068.00
Summary
In clinical transplantation, rejection remains the greatest problem in determining both short and long-term patient outcomes. Tolerance, the ability of the body to accept a transplant without immunosuppressive drugs, remains an as yet unattained goal. The aim of this project is to examine the mechanisms by which the initial immune response (innate immunity) affects the development of tolerance or rejection in a mouse model of kidney transplantation.
The Role Of Mucosal-associated Invariant T (MAIT) Cells And Gut Micro-biota In The Pathogenesis Of Paediatric Autoimmune Liver Disease (AILD).
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
Liver disease can develop when a faulty immune system attacks the liver, occasionally leading to significant liver scarring and liver transplantation. Children who develop this condition need life-long treatment, but not every child responds. I intend to study immune cells and their activity in the blood and liver of affected children. By identifying the role of the immune system in liver inflammation, we hope to find out why children develop this disease and how best to treat them.
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
The Impact Of The Identification And Inclusion Of Acceptable HLA-mismatches On The Transplant Potential Of Highly-sensitised Renal Transplant Candidates.
Funder
National Health and Medical Research Council
Funding Amount
$100,323.00
Summary
In Australia, allocation of donor kidneys are currently weighted largely on the degree of donor-recipient HLA compatibility. However, not all HLA mismatches leads to negative outcomes. Acceptable HLA-mismatches are antigen mismatches that can be considered compatible at a structural and functional level and have been applied to circumvent the problem of difficulty finding suitable donors for highly-sensitised transplant candidates. We apply this concept to the Australian kidney transplant popula ....In Australia, allocation of donor kidneys are currently weighted largely on the degree of donor-recipient HLA compatibility. However, not all HLA mismatches leads to negative outcomes. Acceptable HLA-mismatches are antigen mismatches that can be considered compatible at a structural and functional level and have been applied to circumvent the problem of difficulty finding suitable donors for highly-sensitised transplant candidates. We apply this concept to the Australian kidney transplant population.Read moreRead less
The Role And Function Of Macrophages In Cellular Xenograft Rejection
Funder
National Health and Medical Research Council
Funding Amount
$323,250.00
Summary
The long term objective of this project is to develop pig insulin secreting tissue as a treatment for type 1 diabetes. At present the main barrier to this is rejection. In paricular a type of white blood cell called macophages has an important role in causing the rejection seen in xenotransplantation (the transplantation of pig tissue into humans). Our reseach group has made novel observations which show that the way macrophages respond to a xenotransplant is different to the way it behaves to t ....The long term objective of this project is to develop pig insulin secreting tissue as a treatment for type 1 diabetes. At present the main barrier to this is rejection. In paricular a type of white blood cell called macophages has an important role in causing the rejection seen in xenotransplantation (the transplantation of pig tissue into humans). Our reseach group has made novel observations which show that the way macrophages respond to a xenotransplant is different to the way it behaves to the transplant of an organ from the same species. In the rejection of pig insulin secreting tissue, macrophages are able to respond in the absence of ongoing signals from T cells. This project aims to identify the receptors on macrophages that are responsible for this response. In particular those receptors that are important for facilitating the migration of macrophages to the transplant site and the receptors that allow macrophages to distinguish self from non-self will be analysed. Hopefully these receptors will be used as targets for new therapeutic agents that could be used to prevent the strong rejection response that occurs when pig insulin secreting tissue is transplanted into humans.Read moreRead less