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
Role Of Hypoxia Inducible Factor In Innate Immune Function Against Gram-positive Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$241,352.00
Summary
Our society is currently facing the rise of drug-resistant pathogens ("superbugs") such as the potentially devastating methicillin-resistant Staphylococcus aureus, or _MRSA�. Recently, a molecule known as HIF has been shown to control the ability of our white blood cells to kill bacteria. This proposal aims to investigate the use of HIF boosting drugs to treat infections. These novel HIF agonists could be used alongside conventional antibiotics to improve infectious disease.
Despite recent advances in therapeutic options, chronic viral infections, including infection with hepatitis C virus and hepatitis B virus, continue to be a significant cause of morbidity and mortality in Australia and affecting hundreds of millions of people worldwide. This R&D program aims to develop a cheaper drug formulation that is easier to deliver and more stable for transport to remote areas.
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.
New Mechanisms Of Immunomodulation By Interferon Transsignaling
Funder
National Health and Medical Research Council
Funding Amount
$540,441.00
Summary
The aim of this project is to characterise a new discovery of how the body can regulate its response to disease such as infections and cancer. Interferons are produced by the body to stimulate immune reactions to these diseases. We have dicovered that a circulating form of an interferon binding protein or receptor can change the nature of an immune response. We plan to study how this is achieved and whether this information can be used therapeutically.
Immunopathological Role Of Monocyte-macrophages In Flavivirus Encephalitis.
Funder
National Health and Medical Research Council
Funding Amount
$445,011.00
Summary
Viral encephalitis is a life-threatening infection of the brain for which there are no reliable treatments. White cells called monocytes enter the brain from the blood and although important in the immune response that destroys the virus, can also damage the brain. Our work focuses on determining how monocytes migrate into the brain in viral infection, what functions they have once inside the brain, and how to exclude a certain types of monocytes that we have found to be particularly damaging.
Modulation Of Leishmaniasis By The Proinflammatory Cytokines TNF
Funder
National Health and Medical Research Council
Funding Amount
$288,911.00
Summary
We have established a mouse model that has been genetically modified and cannot produce the cytokine tumour necrosis factor. This cytokine is secreted in the beginning of the inflammatory response. If these mice are infected with a parasite they are not able to heal the infection and die quickly. We can demonstrate that these mice cannot regulate the beginning inflammatory response and do not form a cellular infiltrate at the site of infection.
Regulating Interferon Signalling In Innate Immunity
Funder
National Health and Medical Research Council
Funding Amount
$547,428.00
Summary
Our innate immune system evolved as the front line defence against infection. However an uncontrolled response can lead to serious diseases such as septic shock, chronic inflammation as in hepatitis, autoimmune diseases such as systemic lupus erythematosus. The immune respnse is regulated by important hormones such as interferon produced by the body in these situations. This project aims to understand the negative or inhibitory mechanisms that prevent dangerous side effects of interferons withou ....Our innate immune system evolved as the front line defence against infection. However an uncontrolled response can lead to serious diseases such as septic shock, chronic inflammation as in hepatitis, autoimmune diseases such as systemic lupus erythematosus. The immune respnse is regulated by important hormones such as interferon produced by the body in these situations. This project aims to understand the negative or inhibitory mechanisms that prevent dangerous side effects of interferons without restricting their postive or beneficial effects. We will examine the actions of a molecule called the Suppressor of cytokin Signaling 1 (socs1) which we have recently discovered to modulate the actions of interferon in the mouse. Initially our studies will determine which molecules SOCS1 binds to inside a cell and the consequences for cell activation pathways. The next step will be to specifically block this interaction in the mouse and determine the effects on models of viral infection and inflammatory disease. The outcome of these studies will be a better understanding of how the body fights disease via the immune response and potential new approaches to develop therapeutic drugs.Read moreRead less
Bacterial Outer Membrane Vesicles As Immunomodulatory Agents In Helicobacter Pylori Infection
Funder
National Health and Medical Research Council
Funding Amount
$306,510.00
Summary
Chronic inflammation of the stomach is a hallmark of Helicobacter pylori infection, and is a precursor to peptic ulcer disease and cancer. Like many other bacteria, H. pylori sheds spherical blebs from its surface. These blebs bind to stomach cells in vitro and have been found in stomach biopsies of H. pylori-infected subjects. The aims of the work are to investigate the mechanisms whereby H. pylori blebs enter and disseminate within host cells, and how this may contribute to inflammation.
Immunomodulatory Molecules Of Parasitic Helminths As Novel Therapeutics For Allergic Disorders.
Funder
National Health and Medical Research Council
Funding Amount
$321,532.00
Summary
Australia has one of the highest rates of asthma in the world with almost 3 million Australians are affected by this disease. Previous research has shown that infection with various types of parasitic worms lessens the severity of asthma. The aim of this research is to find out why this happens and to isolate the ingredients from the parasite that suppress asthma. Once found, these molecules can be used to create new drugs for the prevention of asthma and allergies in children and adults.