The Role Of Non-classical MHC Class I Molecules In Adaptive Immunity
Funder
National Health and Medical Research Council
Funding Amount
$443,834.00
Summary
Specialised proteins called MHC class Ia molecules (MHC-Ia) stimulate killer T cells to lyse virus infected cells. In contrast, the function of the closely related MHC-Ib is uncertain. Recent findings have demonstrated that MHC-Ib can also be recognised by T cells and this interaction is important in the control of viral infections. However, despite the similarity to MHC-Ia, it is unclear how this interaction occurs. This project aims to investigate how killer T cells recognise MHC-Ib molecules.
The Role Of Co-signalling Receptors In Cytotoxic Lymphocyte Activity During Infection And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$739,657.00
Summary
Cytotoxic lymphocytes (CLs) are immune cells that detect and kill cancer cells. CLs recognise ‘stress’ proteins on cancer cells through specialised receptors, and this provides the signal for them to kill. However, some cancer cells, such as leukemic cells, can interfere with this recognition to avoid killing by immune cells. This project will investigate the mechanism of recognition and killing of cancer cells by CLs, using both mouse models and cells from patients with acute myeloid leukemia.
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
Novel Approaches For Activation And Expansion Of Genetically Modified T Cells In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$115,660.00
Summary
Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engi ....Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engineered in culture with tumor recognition receptors. When transferred into mice, these genetically engineered cells can release toxic and inflammatory proteins that cause tumor destruction. In this proposal we wish to further test this approach in mice by enginneering the mouse killer T cells with (i) receptors that provide stronger signals for killing and proliferation; and (ii) with receptors targeting other structures on tumor cells including the tumor vasculature as a means to overcome tumor escape. In addition, we wish to test a novel approach of combining both genetic engineering and vaccination strategies for expanding gene-modified cells after adoptive transfer. These studies will allow the best receptor genes to be transferred to human white blood cells and examined for anti-tumor effects in immune-deficient mice.Read moreRead less
Developing Diagnostics And Therapeutics For Preeclampsia: Targeting A Novel Placental Specific SFlt-1 Variant
Funder
National Health and Medical Research Council
Funding Amount
$722,283.00
Summary
Preeclampsia is a dreaded disease of pregnancy, globally responsible for thousands of deaths of mothers and babies. It is caused by a protein called sFlt-1 leaking out of the placenta and attacking the mothers organs. Recently, a new sflt-1 subtype was discovered that is specific to the placenta. It may be the key disease causing toxin in preeclampsia. We will target this placental specific sFlt-1 to generate diagnostics to predict preeclampsia, and explore novel ways to block the toxic effects ....Preeclampsia is a dreaded disease of pregnancy, globally responsible for thousands of deaths of mothers and babies. It is caused by a protein called sFlt-1 leaking out of the placenta and attacking the mothers organs. Recently, a new sflt-1 subtype was discovered that is specific to the placenta. It may be the key disease causing toxin in preeclampsia. We will target this placental specific sFlt-1 to generate diagnostics to predict preeclampsia, and explore novel ways to block the toxic effects of sFlt-1 as a strategy to develop drugs.Read moreRead less
Nanomedicine Targeted Delivery Of Therapeutics To The Placenta To Treat Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$513,148.00
Summary
Preeclampsia, one of the most serious complications of pregnancy, affects around 3-8% of all pregnancies. Sadly, there is no treatment. We have developed a new technique to deliver treatments only to the placenta, sparing the mother and baby from side effects. We will test whether this technique can treat the source of preeclampsia, the placenta, in human and mouse models in our laboratory. This work has potential to offer possibilities of new treatments to other pregnancy complications.
Systematic Screening Approach To Identify New Therapeutics For Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$727,529.00
Summary
Preeclampsia is a pregnancy complication where factors are released from the placenta into the mum's bloodstream, causing widespread blood vessel and organ damage. Sadly, there is no treatment. Our laboratory has a set up a system to test whether drugs might be useful as a treatment for preeclampsia. We test whether the drugs decrease the release of these factors and protect blood vessels. In this grant, we propose testing three exciting drug treatments for preeclampsia.
Translating New Therapeutics And Diagnostics For Major Pregnancy Complications
Funder
National Health and Medical Research Council
Funding Amount
$481,156.00
Summary
My research is focussed on tackling major complications of pregnancy that are a threat to the lives of both mother’s and babies. We are developing new drug treatments for ectopic pregnancy (a dangerous condition where the pregnancy implants in the Fallopian tube), and preeclampsia (a condition where toxins leak out of the placenta into mum's blood, and can seriously injure many of mum's major organs). We are also generating a blood test that may help women avoid the tragedy of a stillbirth.
New Generation Antiplatelet Therapies To Prevent Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$483,148.00
Summary
Preeclampsia, a major complication of pregnancy, affects around 3-8% of pregnancies. Sadly, there is no way to prevent or delay disease. We have uncovered antiplatelet agents, used to prevent heart disease and stroke, may provide health benefits to women at risk of developing preeclampsia. We will test whether these agents can prevent the pathophysiology of preeclampsia in specialized human & mouse models developed in our laboratory. This work may provide a prevention strategy for preeclampsia.