We have identified a microRNA (miRNA) which can elicit the functional outcome of the anti-inflammatory cytokine IL-10. miRNAs constitute a novel mechanism used by cells to regulate gene expression and have shown much promise as a therapeutic tool. Our finding suggests that modulation of miRNAs through the use of miRNA mimics or antisense technology may serve as an alternative and/or synergistic approach for the use of IL-10 as therapy in chronic inflammation.
During injury or infection, our body’s immune system protects us by launching inflammation. But uncontrolled inflammation drives common diseases such as cancer, diabetes and Alzheimer’s. This project will reveal how the body produces interleukin-1? – a protein at the heart of inflammation and disease – so we can design better strategies for treating patients with inflammation-driven disease.
Excess inflammation is a major problem after injury and in many diseases. Upon injury molecules are release that act as danger signals to alert the immune system to start the repair process. However, high levels of these dangers signals can impair the final stages of healing. Understanding how to prevent the immune system being excessively stimulated by these danger signals is key to being able to dampen inflammation after injury improve the healing response.
Unconventional Mechanisms For Activating The NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$747,031.00
Summary
Many inflammatory driven diseases such as arthritis, atherosclerosis and septic shock are also associated with cell death. This project will identify, at the molecular level, how cell death signalling specifically acts to trigger pathological inflammation. As such, it will identify novel targets for the development of next generation anti-inflammatory drugs.
Microbial Evasion Of A Novel Inflammasome By Salmonella
Funder
National Health and Medical Research Council
Funding Amount
$486,174.00
Summary
Microbes quickly evolve to evade detection by the innate immune system, the body’s first line of defence against infection. This project investigates the mechanisms by which the immune system recognises bacterial infection, and pathways used by bacteria to avoid these defences. This research will lead to a better understanding of mechanisms underlying resistance and susceptibility to bacterial infection.
The Regulatory Role Of Clec12A In Antigen Presentation And Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,381,077.00
Summary
The immune system maintains a balance between initiating immune responses to infections and suppressing immune responses in health. We have identified, on the surface of specialised immune cells, a protein that is critical for regulating immune responses and dampening down inflammation. This proposal aims to determine how this protein functions in health and under inflammatory conditions, and to develop approaches based on its molecular interactions to reduce inflammatory disease.
THE ROLE OF THE TETRASPANINS CD37 AND CD82 IN LEUKOCYTE MIGRATION
Funder
National Health and Medical Research Council
Funding Amount
$370,902.00
Summary
White blood cells must be able to migrate to fight infection. For instance, immune responses are started by the migration of one type of white blood cells to the lymph node. Also, once activated white blood cells migrate out of the circulation to the site of infection where they can kill bacteria and viruses. This grant studies 2 proteins that control white blood cell migration. These proteins may one day be targets for drugs that either promote immunity or reduce inflammation.
Mechanisms Of Alpha-hemolysin Induced Immunoevasion By Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$465,475.00
Summary
S. aureus infections represent a serious global health problem. Currently, no vaccination is available demanding a better understanding of the immune response against this bacterium. We will test the hypothesis that S. aureus alpha-hemolysin represses the migration of innate immune cells to sites of cutaneous infection resulting in diminished immunity. Unraveling the mechanism behind this phenomenon will pave the way to better prophylactic and therapeutic measures against S. aureus infections.
Neutrophil Regulation Of Early Adaptive Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$613,273.00
Summary
The aim of this project is to utilise novel mouse models and imaging techniques to unravel the role of an immune cell called neutrophil in controlling immune responses. We show that as the first cell to leave the site of bacterial infection neutrophils can orchestrate subsequent activation of other immune cells. We plan to investigate the mechanisms and consequences of this process with a view to uncover new neutrophil-based therapeutic strategies that would improve the management of inflammator ....The aim of this project is to utilise novel mouse models and imaging techniques to unravel the role of an immune cell called neutrophil in controlling immune responses. We show that as the first cell to leave the site of bacterial infection neutrophils can orchestrate subsequent activation of other immune cells. We plan to investigate the mechanisms and consequences of this process with a view to uncover new neutrophil-based therapeutic strategies that would improve the management of inflammatory diseases.Read moreRead less
The Role Of IL-17 In Regulating Liver Macrophage Permissiveness For Leishmania Infection
Funder
National Health and Medical Research Council
Funding Amount
$655,082.00
Summary
Visceral Leishmaniasis is a disease of poverty in the developing world caused by Leishmania parasites, which live and replicate within host tissue macrophages. A cytokine produced by host cells, IL-17A impairs the ability of liver macrophages to control this infection, as mice that lack IL-17A have lower parasite burdens in the liver after experimental infection. We propose to investigate if IL-17A mediates this impaired control by tuning the permissiveness of host macrophages to infection.