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The Role Of Interleukin-21 In The Pathogenesis Of Autoimmune Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$489,060.00
Summary
Interleukin-21 (IL-21) is a soluble protein that is produced by cells enabling them to communicate with other cells. IL-21 helps cells to clear viruses and bacteria from the body. However, our studies show that IL-21 also generates T cells that destroy beta cells and cause diabetes. IL-21 is produced at abnormally high levels in an important murine model of spontaneous type-1 diabetes (T1D) and if we block IL-21 we prevent diabetes. This projects' aims assess IL-21 as therapeutic target for T1D.
The Role Of Interleukin-21 In The Pathogenesis Of Autoimmune Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$519,000.00
Summary
T cells are a component of our blood (white blood cells) and a major component of the body's defense system against infection, known as immunity. Without T cells, we would fail to resist infection by foreign agents, such as viruses, bacteria and fungi. Autoimmune (type 1) diabetes is a disease in which T cells attack our own pancreatic islet self tissues as if they were foreign. T cells that react against the islets of the pancreas cause destruction of the insulin producing beta cells so that th ....T cells are a component of our blood (white blood cells) and a major component of the body's defense system against infection, known as immunity. Without T cells, we would fail to resist infection by foreign agents, such as viruses, bacteria and fungi. Autoimmune (type 1) diabetes is a disease in which T cells attack our own pancreatic islet self tissues as if they were foreign. T cells that react against the islets of the pancreas cause destruction of the insulin producing beta cells so that the pancreas can no longer make insulin. Diabetes is a life-threatening disease because insulin is a hormone that enables people to get energy from food. Type 1 diabetes is usually diagnosed in childhood and insulin must be administered daily by injection or through a pump in order to survive. Unfortunately, taking insulin doesn t cure diabetes and people continue to suffer from an extensive list of complications affecting most vital organs. Interleukin-21 (IL-21) is a soluble protein that is produced by cells enabling them to communicate with other cells. IL-21 helps cells to produce factors that cause inflammation and assist in clearance of viruses and bacteria from the body. However, our studies show that IL-21 is a major factor in the development of the T cells that destroy beta cells and cause diabetes. Our studies show that IL-21 is over-expressed in an important murine model of spontaneous type-1 diabetes. We have isolated the T cells that cause diabetes and show that they are distinguished from other T cells by very high levels of the receptor for IL-21. This project focuses on the IL-21-responsive T cells that cause diabetes and aims to determine the mechanisms by which the cytokine IL-21 causes destructive immune responses and ways to modulate its production. This project applies basic science to the important public health issue of type 1 diabetes for the development of therapeutic intervention strategies.Read moreRead less
Interactions Between IL-15 And TGF-beta Signalling Pathways Reveal Novel Therapeutic Strategies To Boost Anti-cancer Immunity
Funder
National Health and Medical Research Council
Funding Amount
$444,425.00
Summary
This project will determine if new immune inhibitory checkpoints can be synergistically targeted with BRAFV600E inhibition to reactivate and allow NK cells to maximise their anti-tumour immune functions and prevent cancer spread. It is a completely novel approach that will allow for the more rational design of melanoma treatments that targets NK cells following surgery and local radiotherapy and/or chemotherapy.
Investigating The Utility Of Therapeutic Drug Monitoring Of Beta-lactam Antibiotics In Hospitalised Patients
Funder
National Health and Medical Research Council
Funding Amount
$215,887.00
Summary
The appropriate dosing of antibiotics for patients admitted to hospital is based on broad guidelines derived from studies in healthy volunteers or in patients that may have different types of infections. Minor changes in the clinical state of the patients can require significant dosing adjustments. The best way to guarantee appropriate antibiotic therapy is to individualize doses based on blood concentration data. We aim to determine the utility of dose adjustment in hospitalized patients.
Life Threatening Cancer Across The Lifespan: Examining The Relevance Of Music To Patients And Their Companions
Funder
National Health and Medical Research Council
Funding Amount
$137,000.00
Summary
Although music is widely used, scant discussion about its therapeutic merit exists when compared to the spoken word. Throughout the Ages, ritualized music promoted health and loss adjustment, however, music is not pivotal in modern medicine. The research will examine people’s intuitive music usage when experiencing life threatening cancer and the relationship between music therapy participation and one’s later music experience. Findings will inform specific recommendations for music therapists a ....Although music is widely used, scant discussion about its therapeutic merit exists when compared to the spoken word. Throughout the Ages, ritualized music promoted health and loss adjustment, however, music is not pivotal in modern medicine. The research will examine people’s intuitive music usage when experiencing life threatening cancer and the relationship between music therapy participation and one’s later music experience. Findings will inform specific recommendations for music therapists and generic guidelines to extend music’s therapeutic effect in palliative care.Read moreRead less
Osteoclasts (OC) are large multinucleated cells present in bone that are responsible for bone resorption. The renewal of bone and bone growth are regulated by the opposing actions of OCs and osteoblasts, cells that form new bone. Together, with other accessory cells in the bone marrow, these constitute 'bone-forming units' (BFU). Excess production or over-activation of OCs in the BFU leads to common bone conditions such as osteoporosis, Paget's disease and the bone lysis caused by bone cancers. ....Osteoclasts (OC) are large multinucleated cells present in bone that are responsible for bone resorption. The renewal of bone and bone growth are regulated by the opposing actions of OCs and osteoblasts, cells that form new bone. Together, with other accessory cells in the bone marrow, these constitute 'bone-forming units' (BFU). Excess production or over-activation of OCs in the BFU leads to common bone conditions such as osteoporosis, Paget's disease and the bone lysis caused by bone cancers. Osteoporosis causes a great deal of pain and disability and it alone costs the Australian taxpayers more than $400 million per year. OCs are formed from white blood cells that are present in the bone marrow and the blood. The recent discovery of a family of new factors that control the formation of OCs has enabled the generation of human OCs in the laboratory so now we can investigate the genes that control the process of conversion of white blood cells to OCs. An important advance in this project involves the use of cord blood that contains stem cells. These very na ve cells will enable us to study the very earliest genes that control differentiation of precursors to OC. We have found a number of genes that are regulated by these new bone-forming factors. In white blood cells the activation of particular genes can regulate OC formation. One example is vitamin D-upregulated gene, VDUP. This gene is of particular interest as it causes inhibition of the mechanism that leads to OC formation in the bone. Obviously, the ability to control a 'switch' that regulates OC formation may enable us to control the progress of bone loss in diseases such as osteoporosis. In this project, we intend to investigate how and why the genes that lead to OC formation are regulated and what influence the various bone cell factors have on the formation of bone-resorbing OCs. These studies will lead to the development of treatments for osteoporosis and other bone diseases.Read moreRead less
Diabetes mellitus is a disease reaching epidemic proprotions in the western world. Nearly one million Australians have diabetes mellitus; many of these people will suffer debilitating secondary complications, resulting in significant morbidity and mortality at considerable social and economic cost. Complications include heart attack, stroke, kidney disaease, blindness and limb amputation. There are two forms of diabetes (type I and type 2), and though there are considerable differences in their ....Diabetes mellitus is a disease reaching epidemic proprotions in the western world. Nearly one million Australians have diabetes mellitus; many of these people will suffer debilitating secondary complications, resulting in significant morbidity and mortality at considerable social and economic cost. Complications include heart attack, stroke, kidney disaease, blindness and limb amputation. There are two forms of diabetes (type I and type 2), and though there are considerable differences in their etiology, both forms result in an inability of the body to control blood sugar levels. Beta cells release the hormone insulin, which regulates blood sugar levels. Current knowledge suggests that a loss of beta cell mass is important for both diseases. For type I diabetes the beta cells are destroyed by the immune system. Though for type 2 diabetes the causes are less clear, it is apparent that the beta cells are dying. Our research is focused on understanding the molecular pathways that control beta cell survival and regulate their death. Such knowledge would help us understand the complex processes leading to the development of diabetes. Furthermore, we could use this knowledge in the design of genetic engineering strategies to create 'death-defying' beta cells, as a potential therapeutic strategy for the treatment of diabetes.Read moreRead less
Central Control Of Stress-induced Changes In Immune Function.
Funder
National Health and Medical Research Council
Funding Amount
$411,724.00
Summary
LONG-TERM STRESS CAN ALTER OUR BRAIN'S ATTEMPTS TO FIGHT INFECTION Long-term stress is often blamed for causing illness but precisely how this occurs is now only beginning to be realised. It is especially disturbing that long-term stress can increase one's susceptibility to infections. Stress can alter the way our brain can help deal with assaults by bacteria and viruses. Normally, at the start of an infection, we release a hormone called cortisol from our adrenal glands. A low level of cortisol ....LONG-TERM STRESS CAN ALTER OUR BRAIN'S ATTEMPTS TO FIGHT INFECTION Long-term stress is often blamed for causing illness but precisely how this occurs is now only beginning to be realised. It is especially disturbing that long-term stress can increase one's susceptibility to infections. Stress can alter the way our brain can help deal with assaults by bacteria and viruses. Normally, at the start of an infection, we release a hormone called cortisol from our adrenal glands. A low level of cortisol in our body is beneficial because it can prevent the infection from taking hold in our body and spreading. However if we are chronically stressed our brains tell the adrenal glands to secrete excessive amounts of cortisol over long periods of time and this imbalance can actually hinder the ability of one's immune system to fight an infection. The unfortunate consequence is that the infection is more likely to win the battle and spread to cause further havoc. The present study will identify which areas of the brain are important in driving the secretion of cortisol during infection and how long-term stress can influence those areas. Because we might be exposed to long-term psychological stress that is repeated regularly or irregularly we will determine which pattern of stress has the greatest effect. An investigation into how the brain operates during long-term stress and infection will help us develop ways to prevent stress from disrupting our immune systems.Read moreRead less
The Generation And Function Of Tissue-specific Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$488,577.00
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. We will discover how regulatory lymphocytes, are able to protect against autoimmune disease. Such regulatory lymphocytes are attractive therapeutic agents to prevent a variety of immune-mediated diseases, including autoimmune diseases, allergy and transplantation rejection.