Understanding Natural Killer Cell Development And Target Recognition
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
Immune detection and eradication or control of cancer and cancer immunotherapies are based in part on the idea that tumour-specific white blood cells can protect the body from tumour development, growth and metastases. While strong evidence supports this, the means by which these white cells first recognize the cancerous tissue is largely unknown. We will study a new family of white blood cell receptors that may be important in this recognition, either naturally or following therapy.
Defining The Roles Of TNF, Lymphotoxin Alpha And LIGHT In Experimental Visceral Leishmaniasis
Funder
National Health and Medical Research Council
Funding Amount
$410,148.00
Summary
Visceral leishmaniasis (VL) is an important human disease caused by the protozoan parasites Leishmania donovani and L. infantum (chagasi). Studies in experimental VL caused by L. donovani infection of mice have resulted in major insights into the causes of VL and the reasons why VL patients become severely immunocompromised. Work from our laboratory has shown that members of the TNF family of cytokines play key roles in the generation of effective immune responses during VL, but also mediate sig ....Visceral leishmaniasis (VL) is an important human disease caused by the protozoan parasites Leishmania donovani and L. infantum (chagasi). Studies in experimental VL caused by L. donovani infection of mice have resulted in major insights into the causes of VL and the reasons why VL patients become severely immunocompromised. Work from our laboratory has shown that members of the TNF family of cytokines play key roles in the generation of effective immune responses during VL, but also mediate significant tissue pathology, particularly in the spleen, following L. donovani infection. In this grant, we will define the roles of several key members of the TNF family in the generation of immunity and pathology during experimental VL. We will also test if the activity of these molecules can be modulated to control disease without detrimental side effects. Results from this research have implication for the design of new vaccines and therapeutics to control VL. In addition, given the important role of TNF family members in cancers and autoimmune diseases, the work in this grant will have advance our understanding of pathogenic processes that are common to many important human diseases.Read moreRead less
Organ-specific Autoimmunity: The Role Of The Thymus And Periphery In Shaping The Gastric-specific T Cell Repertoire
Funder
National Health and Medical Research Council
Funding Amount
$579,763.00
Summary
The immune system normally protects against invasion by pathogens such as harmful viruses and bacteria. In autoimmune diseases the same mechanisms that are used to protect us are erroneously targeted to our own tissues. White blood cells, called T lymphocytes are responsible for attacking our own tissues in autoimmune diseases. Our studies will employ a range of molecular, genetic and imaging technologies to track the rare and potential harmful white blood cells. Our studies should reveal the me ....The immune system normally protects against invasion by pathogens such as harmful viruses and bacteria. In autoimmune diseases the same mechanisms that are used to protect us are erroneously targeted to our own tissues. White blood cells, called T lymphocytes are responsible for attacking our own tissues in autoimmune diseases. Our studies will employ a range of molecular, genetic and imaging technologies to track the rare and potential harmful white blood cells. Our studies should reveal the mechanisms by which these self destructive T lymphocytes are silenced in healthy individuals on the one hand, and on the other hand escape to cause destruction in individuals with autoimmune diseases. This fundamental information will allow the development of therapeutic strategies to selectively turn-off these destructive T lymphoctyes in individuals with autoimmune disease and thereby remove the damaging immune response and cure the disease.Read moreRead less
Immunopathogenesis Of Organ-specific Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$284,638.00
Summary
The immune system normally protects against invasion by pathogens such as harmful viruses and bacteria. In autoimmune diseases the same mechanisms that are used to protect us are erroneously targeted to our own tissues. Our studies will employ state-of-the art technologies to further our knowledge of this class of diseases and to uncover the normal mechanisms that allow the immune system to differentiate foreign and self components.
Hormonal Resuscitation And P38 MAP Kinase Inhibition To Enhance Quality Of Cadaveric Donor Organs For Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
The transplantation of organs such as the heart, lung, liver, kidney and pancreas from brain-dead donors is limited primarily by the shortage of donor organs. It is now recognised that as many as 25% (one in four) potentially usuable donor organs are lost after brain death due to the rapid deterioration that occurs in organs after brain death. There is evidence that this deterioration is due to loss of the normal hormones that are essential to the normal functioning of these organs. In this proj ....The transplantation of organs such as the heart, lung, liver, kidney and pancreas from brain-dead donors is limited primarily by the shortage of donor organs. It is now recognised that as many as 25% (one in four) potentially usuable donor organs are lost after brain death due to the rapid deterioration that occurs in organs after brain death. There is evidence that this deterioration is due to loss of the normal hormones that are essential to the normal functioning of these organs. In this project, we will use a pig model of brain death that we have extablished in our laboratory to examine the effects of hormone replacement on the function of organs that are used for transplantation. We will also test a novel drug aimed at protecting donor organs during the period between removal of the organ and transplantation. If successful, these treatments have the potential to markedly increase the numbers of organ transplants and to improve the outcomes for recipients of these transplants. In the Australian and New Zealand setting, a 25% increase in the number of donor organs would results in approximately 220 more people per year receiving these life-saving operations.Read moreRead less
Investigating T Cell Tolerance And Organ-specific Auotimmunity Using Autoantigen Deficient Mice
Funder
National Health and Medical Research Council
Funding Amount
$441,000.00
Summary
The immune system normally protects against invasion by pathogens such as harmful viruses and bacteria. In autoimmune diseases the same mechanisms that are used to protect us are erroneously targeted to our own tissues. Our studies will employ technologies to genetically manipulate mice to further our knowledge of this class of disease and to uncover the normal mechanisms that allow the immune system to prevent autoimmune attack. In particular we will gain information on the way that a new class ....The immune system normally protects against invasion by pathogens such as harmful viruses and bacteria. In autoimmune diseases the same mechanisms that are used to protect us are erroneously targeted to our own tissues. Our studies will employ technologies to genetically manipulate mice to further our knowledge of this class of disease and to uncover the normal mechanisms that allow the immune system to prevent autoimmune attack. In particular we will gain information on the way that a new class of lymphocytes, known as regulatory lymphocytes, are able to protect against autoimmune disease. Such regulatory lymphocytes have been identified in humans and are attractive therapeutic agents to prevent a variety of immune-mediated diseases, including autoimmune diseases, allergy and transplantation rejection.Read moreRead less
Global Data Mapping And Evaluation Of Needs, Capacities And Benchmarks In Organ Donation And Transplantation: Informing Effective Local And International Health Policy To Better Meet The Needs Of Patients
Funder
National Health and Medical Research Council
Funding Amount
$318,575.00
Summary
Global shortages of donor organs limit the provision of reliable and equitable access to solid organ transplantation. As a result, many are excluded from waiting lists, others deteriorate whilst awaiting transplantation, and some seek to purchase the needed organ. Countries have a responsibility to provide transplantation services sufficient to meet population need. This project evaluates international data for key interventions that may impact on waitlisting, donation and transplant practices.
Stem Cell Engineering To Establish Tolerance And Reverse Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$497,250.00
Summary
The immune system is designed to protect us from harmful invaders such as bacteria, viruses and parasites. It should not attack our own tissues. However, in certain individuals, the immune system does attack our own tissues leading to life threatening conditions such as diabetes, multiple sclerosis and rheumatoid arthritis. To date, there is no cure for autoimmune diseases. Treatment is designed to treat the destructive effects of the disease. A strategy for achieving a cure is to program the im ....The immune system is designed to protect us from harmful invaders such as bacteria, viruses and parasites. It should not attack our own tissues. However, in certain individuals, the immune system does attack our own tissues leading to life threatening conditions such as diabetes, multiple sclerosis and rheumatoid arthritis. To date, there is no cure for autoimmune diseases. Treatment is designed to treat the destructive effects of the disease. A strategy for achieving a cure is to program the immune system to remove the harmful immune cells. Autoimmune gastritis which leads to pernicious anaemia is an autoimmune disease which affects the acid secreting cells of the stomach. To get a better understanding of autoimmune diseases, animal models are often used. We use a number of mouse models of autoimmune gastritis which closely resembles the human disease and thus makes a very good working model. Using these models we are exploring novel techniques aimed at reversing or curing established disease. This relies on removing the disease causing cells from the body and re-programming the immune system so as not to produce these cells.Read moreRead less
Improved Patient Outcomes Through Dosage Individualisation Of The Newer Immunosuppressant Drugs
Funder
National Health and Medical Research Council
Funding Amount
$486,206.00
Summary
After organ transplantation, recipients need to take medicines continually to stop their immune system from rejecting their new organ. This treatment with immunosuppressant drugs is vital for long-term success of their graft. However, too many people are losing their transplant or are experiencing drug toxicity or infection due to poorly managed immunosuppression. The project aims to accurately define the best way to dose newer immunosuppressant drugs in Australian transplant populations.