HMGB1: A Novel Player In The Pathogenesis Of Inflammatory Myositis?
Funder
National Health and Medical Research Council
Funding Amount
$84,800.00
Summary
The project aims to determine whether HMGB1, a pro-inflammatory molecule, plays a key role in the cause of inflammatory myositis, an extremely disabling muscle condition characterised by progressive weakness.
Chronic infectious diseases have a devastating effect on global health. HIV and Plasmodium falciparum both cause chronic disease and have evaded effective vaccine design. Vaccines rely on immune memory – the ability to clear an infection rapidly to a previously encountered pathogen. This proposal investigates the formation and dysfunction of immune memory in chronic infectious diseases, which will be vital for creating new and effective vaccines.
The Role Of IL-18 In Proliferative And Crescentic Glomerulonephritis
Funder
National Health and Medical Research Council
Funding Amount
$56,177.00
Summary
Inflammation of the small filters with the kidneys, known as glomerulonephritis, is the commonest cause of kidney failure in Australia. People whose kidneys have failed need either kidney dialysis or a kidney transplant. Our understanding of the immune events that cause glomerulonephritis is patchy. However, it is known that T cells are the directors of immune responses in the body and direct the immune response in glomerulonephritis. Chemical messengers known as cytokines direct the way T cells ....Inflammation of the small filters with the kidneys, known as glomerulonephritis, is the commonest cause of kidney failure in Australia. People whose kidneys have failed need either kidney dialysis or a kidney transplant. Our understanding of the immune events that cause glomerulonephritis is patchy. However, it is known that T cells are the directors of immune responses in the body and direct the immune response in glomerulonephritis. Chemical messengers known as cytokines direct the way T cells behave. One of these cytokines, known as interleukin-18, has been shown to stimulate T cells and other immune cells to induce inflammation that is helpful when the body is fighting infection but is harmful in immune diseases. This project will determine the role of interleukin-18 in glomerulonephritis by studying the way it talks to T cells and the mechanisms by which it incites inflammation in the kidney. Mice with glomerulonephritis will be treated by blocking the actions of interleukin-18 to discover whether interleukin-18 produced by the animal is important in kidney damage induced by glomerulonephritis, to understand the way in which this cytokine works and to assess whether blocking interleukin-18 could be a useful treatment for glomerulonephritis in humans. Current treatments for glomerulonephritis are often ineffective and have unwanted side effects. Knowledge of the way interleukin-18 participates in the immune response in glomerulonephritis may lead directly or indirectly to more effective and more targeted treatments for different forms of glomerulonephritis.Read moreRead less
I am an immunologist studying host immune responses during malaria and visceral leishmaniasis, two important human infectious diseases. I aim to identify immune responses that promote safe and effective control of parasite growth and distinguish them from
Generation And Maintenance Of Effective T Cell Memory In Peripheral Organs
Funder
National Health and Medical Research Council
Funding Amount
$336,767.00
Summary
Infectious diseases represent potentially life-threatening events. Immunity against re-infection relies on different types of memory immune cells that constantly patrol through the organism in search for invading agents. Recently, it has emerged that there exists an additional type of memory cells that permanently reside in peripheral tissues where they confer immediate immune protection. This project will examine the requirements for the generation and maintenance of this important cell type.
Delineating Aberrant Adaptive Immune Responses Due To Germline Mutations In The PI3K Signalling Pathway
Funder
National Health and Medical Research Council
Funding Amount
$975,476.00
Summary
Activation of immune cells is required to generate appropriate immune responses that protect is from disease caused by pathogens. The inability to receive the correct type of signals causes immunodeficiency. The PI3 kinase pathway is central to immune cell activation – and genetic errors in this pathwat compromise the functioning of immune cells. We will investigate the nature of these defects and pursue avenues of overcoming them using pharmacological inhibitors of the PI3K pathway.
Monoclonal Antibodies Targeting Plasma Cells As Novel Therapeutic Agents And Diagnostic Tools
Funder
National Health and Medical Research Council
Funding Amount
$199,275.00
Summary
We have a new tool to identify a very rare immune cell type. This cell makes antibodies, powerful and exquisitely specific proteins that fight infection. In health, antibody-producing cells are beneficial, but in disease (rheumatoid arthritis, lupus and myeloma), these cells cause disease or death. Antibody-producing cells are long-lived. We have no means to specifically deplete them. We are developing reagents to identify and deplete antibody-producing cells to use as novel therapeutic agents.
Ion channels are complex proteins that regulate salt transport in cells. We have previously cloned, and have been studying, an unusual ion channel called CLIC1, whose function is uncertain. Recent data suggests it is located in areas of white cells that are involved in regulating inflammation and mice lacking CLIC1 are protected from some immune disorders. We wish to determine the role and mechanisms whereby CLIC1 regulates immune and inflammatory responses.
Diseases caused by the pneumococcus represent the largest cause of vaccine preventable death in the world today, mainly pneumonia and meningitis. In 2011, 16 developing countries will introduce pneumococcal conjugate vaccines, none in east Asia. Lack of research has been a major barrier to their use in the region. We have established an international centre of excellence in the field and we seek support to extend the capacity of this group and to transfer the technology to Vietnam.
DEVELOPMENT OF CLINICALLY APPLICABLE STRATEGIES TO INDUCE AND MONITOR LONG TERM ACCEPTANCE OF LIVER ALLOGRAFTS
Funder
National Health and Medical Research Council
Funding Amount
$287,036.00
Summary
Liver transplantation is the only therapy for end-stage liver disease and thousands of Australian lives have been saved with this treatment. The major complication of liver transplantation is rejection which leads to loss of about half of the transplanted livers by ten years. Liver transplants in many animal models are not rejected and function normally for the life of the animal. Using one such animal model we have shown that white cells from the donor are responsible for the absence of rejecti ....Liver transplantation is the only therapy for end-stage liver disease and thousands of Australian lives have been saved with this treatment. The major complication of liver transplantation is rejection which leads to loss of about half of the transplanted livers by ten years. Liver transplants in many animal models are not rejected and function normally for the life of the animal. Using one such animal model we have shown that white cells from the donor are responsible for the absence of rejection. Of interest, these cells appear to stimulate a rapid and extreme immune response, which closely resembles rejection. The main difference is that it is quicker and more marked than rejection and then exhausts itself. This observation is unexpected and suggests possibilities for new treatments. Furthermore it questions the effectiveness of our present treatment for rejection of transplanted livers. We have already shown that some kinds of drugs given to prevent rejection in humans actually have the opposite effect in the animal model and prevent long-term acceptance of liver transplants. The aim of this work is to develop in our animal model a better way of treating human liver transplant patients. This will incorporate injection of donor white cells and treatment with drugs which promote the beneficial effects of these cells. We will also develop ways of testing the blood or the liver of the human liver transplant patients early after transplantation to find out whether the patient is accepting the liver or not. This means that we should be able to try this new treatment method in liver transplant patients once it has been optimised in the animal model.Read moreRead less