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
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
The successful treatment of many conditions in which the relevant organ has failed completely and irreversibly is to replace the organ with a new one i.e. to perform a transplant. It is well known that there are far fewer organs available for transplantation than the number needed. This means that for those conditions where a supportive treatment is available, eg. the artificial kidney, patients must be maintained by that method, however for other organs such as hearts, lungs and livers, there i ....The successful treatment of many conditions in which the relevant organ has failed completely and irreversibly is to replace the organ with a new one i.e. to perform a transplant. It is well known that there are far fewer organs available for transplantation than the number needed. This means that for those conditions where a supportive treatment is available, eg. the artificial kidney, patients must be maintained by that method, however for other organs such as hearts, lungs and livers, there is no mechanical substitute. If these patients do not receive a transplant, they die. A solution to this problem is to use organs from animals. This is called xenotransplantation. The pig is the most suitable donor, however despite the many similarities to humans which make pigs suitable, there are many differences which are still to be overcome before we can use pig xenotransplants clinically. These differences are at a very fine molecular level and prevent the normal integration of the pig organ into the human recipient. It is well established that the single most important difference which causes this rejection is a sugar molecule like a blood group which pigs have but humans do not. This is called Gal. This is also present in most animal species and we have completely removed it from a strain of mice by genetic modification. Unfortunately it has not been possible to make this change in pigs. However, the genetically modified mice give us a test model to determine precisely how much and by what mechanisms the Gal antigen is responsible for the rejection process.Read moreRead less
Strategies To Achieve Kidney Transplant Tolerance In A Clinically-relevant Model
Funder
National Health and Medical Research Council
Funding Amount
$663,490.00
Summary
The acceptance of kidney transplants without immunosuppression (tolerance) would avoid the side effects of these powerful drugs and improve long-term graft survival. Donor brain death causes inflammation in transplanted kidneys which can block tolerance. In this project, we aim to determine whether expression of a naturally-occurring soluble anti-inflammatory molecule in the liver can prevent this inflammation, allowing tolerance to develop.
Investigating The Function Of Natural Killer Cells During Immunological Responses Following Human Lung Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$71,766.00
Summary
The immune system is critical in controlling common viral infections in healthy individuals. When transplanting foreign solid organs into patients with end-stage lung disease the immune systemÍs activity is decreased via the immunosuppressive drugs to enable graft acceptance. In some patients the immune response can detect similarities between previously encountered viruses and the foreign organ, leading to life-threatening health problems through either rejection episodes and/or graft loss.
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