A type of white blood cell, the macrophage, is a key player in determining the chronicity of inflammatory conditions such as rheumatoid arthritis, atherosclerosis, psoriasis, nephritis, multiple sclerosis etc. Two particular proteins can control macrophage development and functions, both under normal conditions and during inflammation. The project aims to understand this control. More rational ways to suppress inflammation due to aberrant macrophage function should result.
The Role Of SOCS-1 And SOCS-3 In Regulating Acute Inflammatory Arthritis.
Funder
National Health and Medical Research Council
Funding Amount
$444,910.00
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory disease which mainly targets joints. The disease causes chronic joint pain, stiffness and loss of joint mobility, leading to increasing difficulty in carrying out day to day activities. Treatment for RA has gradually improved, but remains inadequate for many patients. Although the cause is unknown, progress has been made in understanding the molecular pathways which drive RA. The disease is characterised by the production of high levels of infl ....Rheumatoid arthritis (RA) is a chronic inflammatory disease which mainly targets joints. The disease causes chronic joint pain, stiffness and loss of joint mobility, leading to increasing difficulty in carrying out day to day activities. Treatment for RA has gradually improved, but remains inadequate for many patients. Although the cause is unknown, progress has been made in understanding the molecular pathways which drive RA. The disease is characterised by the production of high levels of inflammatory mediators called cytokines. This finding has led to the development and introduction of specific cytokine inhibitors into clinical practice, although a significant number of patients fail to respond to treatment. An alternative approach to develop new treatments for RA would be to use the body's natural inhibitors to limit the actions of inflammatory cytokines. One such inhibitor is Suppressor of Cytokine Signalling-1 (SOCS-1). Using animal models, we have shown that mice lacking SOCS-1 develop more severe arthritis and have identified the different cell types it acts on. Further studies are still needed before SOCS-1 can be developed as a treatment for RA. We aim to identify the major cell type responsible for the increased severity of disease seen when SOCS-1 is absent. This will allow for treatment to be targetted to the most appropriate cells in the joint. We also aim to study the related molecule SOCS-3, to see whether it has similar effects on inhibiting the severity of disease. These studies will provide more information on the activity of SOCS proteins during inflammatory diseases in general and RA in particular and and may lead to new approaches for the treatment of RA.Read moreRead less
MIF Regulation Of MKP-1 And Glucocorticoid Responses In RA
Funder
National Health and Medical Research Council
Funding Amount
$398,156.00
Summary
Rheumatoid arthritis (RA) is a common chronic inflammatory disease which affects 1% of Australians. Up to 70% of patients are treated with 'steroids', which are drugs with major side effects. Recent research has shown that sensitivity to steroids is controlled by a number of natural proteins, and that balance between these proteins controls the effectiveness of steroids. The proposed research will define the interactions between these proteins.
Molecular And Cellular Studies Of The Adaptive Immune Response In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$16,509,154.00
Summary
Immune responses protect us against pathogens such as viruses and bacteria. However inappropriate immune responses can result in autoimmune conditions such as systemic lupus erythmatosus, multiple sclerosis, type I diabetes, asthma as well as immunodeficiencies. The aim of our proposal is to gain a thorough understanding of how all the cells of the immune system function and interact with each other, and what goes wrong when inflammatory diseases develop. We plan to do this using state-of-of-the ....Immune responses protect us against pathogens such as viruses and bacteria. However inappropriate immune responses can result in autoimmune conditions such as systemic lupus erythmatosus, multiple sclerosis, type I diabetes, asthma as well as immunodeficiencies. The aim of our proposal is to gain a thorough understanding of how all the cells of the immune system function and interact with each other, and what goes wrong when inflammatory diseases develop. We plan to do this using state-of-of-the-art technologies, including genetically modified mice, gene microarrays, monoclonal antibodies, and flow cytometry. We have brought together Australia's leading immunologists with complimentary expertise and research interests in specific areas of immunology including cytokines, cell migration, inflammatory diseases, autoimmunity and cell-cell interactions. One aspect of the application is to understand the genetic and molecular basis of immunological diseases. However we also wish to move on from an understanding to treatment of immunological diseases through the development of novel therapeutics. We will form collaborations with biotech and pharmaceutical companies (including our own spin off companies) to advance important new therapeutics for autoimmune and allergic diseases. These conditions represent a significant health burden to Australia.Read moreRead less
Understanding How Endogenous G-CSF Mediates Inflammatory Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$531,485.00
Summary
Rheumatoid Arthritis (RA) is a common chronic inflammatory disease which targets joints. Currently, there is no cure for RA and the available anti-rheumatic drugs have limited efficacy and frequent side effects. Progress has been made in understanding the molecular pathways which drive RA and the disease is characterised by high levels of inflammatory mediators (called cytokines). This finding has led to the development and introduction of specific cytokine inhibitors into clinical practice. The ....Rheumatoid Arthritis (RA) is a common chronic inflammatory disease which targets joints. Currently, there is no cure for RA and the available anti-rheumatic drugs have limited efficacy and frequent side effects. Progress has been made in understanding the molecular pathways which drive RA and the disease is characterised by high levels of inflammatory mediators (called cytokines). This finding has led to the development and introduction of specific cytokine inhibitors into clinical practice. These inhibitors work well for some, but not all, patients. The reason why certain RA patients fail to respond to this treatment is not clear. There is great interest in identifying new cytokines in RA and in developing more effective cytokine inhibitors. Our recent research shows that a cytokine best known for its effect on blood cell development (granulocyte-colony stimulating factor or G-CSF) also plays a major role in experimental models of RA. This discovery has led to two Australian biotechnology companies - Zenyth Therapeutics Ltd., and Murigen Therapeutics Ltd, entering into a partnership to develop G-CSF antagonists for clinical trials. However, before we can take such antagonists to the clinic, we need to conduct careful pre-clinical studies to understand the basis for our findings on G-CSF in much greater detail. This will ensure this new therapy is used in the safest and most effective way.Read moreRead less
Natural Killer (NK) Cells And Development Of Atherosclerosis: Cellular And Molecular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
Atherosclerosis, the accumulation of fat and white cells in the blood vessel wall is the major cause of heart attacks, stroke and death. Cholesterol lowering drugs reduce the risk by only 40%. Targeting cells that promote inflammation is one approach to further reduce risk. We have shown that a specific cell type called a natural killer (NK) cells contributes greatly to development of atherosclerosis. Our aim is to understand how these cells promote development of atherosclerosis.
Laser Acupuncture In Patients With Chronic Knee Pain: A Randomised Placebo-controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$701,120.00
Summary
Chronic knee pain is a common and disabling musculoskeletal condition that causes a loss of functional independence and results in significant health care costs. In the majority of patients the most common cause is osteoarthritis. Acupuncture is a form of non-surgical treatment commonly sought by patients and often recommended by GP's. The main outcomes from our project are to establish the role, clinical effectiveness and cost benefit of laser and needle acupuncture in knee pain patients.
Cell Surface Mucins In Gastrointestinal Infection, Inflammation And Cancer Development
Funder
National Health and Medical Research Council
Funding Amount
$469,627.00
Summary
Cell surface mucins are protective molecules that line all the wet surface of the body, including the gastrointestinal tract. Our research has uncovered that mucins regulate cell growth and cell death. Inappropriate control by the mucins, could lead to chronic inflammation and formation of cancers. We will test how important these molecules are in the development of cancers in the intestine, and further explore the mechanism of action.
Understanding The Interplay Between ER Stress And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$560,918.00
Summary
Chronic inflammatory diseases in the gut and lung affect hundreds of thousands of Australians. We have identified how inflammation causes a type of stress resulting in abnormal protein synthesis in the cells which make the barrier to microbes. Following an infection this process might be the trigger for chronic unresolving inflammatory disease. The further understanding of this process we seek in this project is likely to lead new approaches to treat common inflammatory diseases.
Understanding The Role Of Nociceptin In PMNL-mediated Inflammation In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$474,750.00
Summary
This work will study the role of a type of protein in white blood cell movement into tissues, a process called inflammation. The outcome of this work may lead to the development of molecules which control this movement of white blood cells more specifically than existing therapeutics. Such inhibitors would potentially be useful as anti-inflammatory agents in a range of human diseases.