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.
Il-18 helps to prevent obesity and type 2 diabetes, however the process by which this cytokine is activated to prevent obesity is not known. We have now found the pathway that drives to this process. This project will seek to extend our observations to show how this can be targeted therapeutically to treat obesity and type 2 diabetes.
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.
Many white blood cells have an innate ability to sense infection, and trigger inflammation to fight invading microbes. These innate immune cells use particular receptors to sense pathogens and we have now identified a new pathway that leads to the activation of one of these, known as Pyrin. Genetic mutations can activate this pathway, and our project will determine the molecular basis for this, and how it can be targeted to treat inflammatory disease.
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.
Novel Role Of Inflammasomes In The Molecular Pathogenesis Of Emphysema
Funder
National Health and Medical Research Council
Funding Amount
$764,462.00
Summary
Emphysema is a chronic lung disease that is caused by dysregulation of the immune system, leading to inflammation and destruction of lung tissue. Although emphysema is associated with cigarette smoking, the key components of the immune system which promote emphysema remain ill-defined. Using elaborate mouse models for emphysema, together with biopsies from emphysema patients, our aim is to reveal the role of a protein complex in the immune system called the inflammasome in driving emphysema.
The Inflammasome In Host Defence And Autoinflammation
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
Inflammation is one of the bodies first responses to infection. The inflammasome is a protein complex that activates pro-inflammatory cytokines as part of this process. We are investigating pathogens that activate a specific inflammasome complex, and also an inflammatory disease it may cause when activated accidentally, in the absence of infection. We are also investigating pathways that keep this inflammation in check, and how pathogens might hijack these anti-inflammatory pathways to promote i ....Inflammation is one of the bodies first responses to infection. The inflammasome is a protein complex that activates pro-inflammatory cytokines as part of this process. We are investigating pathogens that activate a specific inflammasome complex, and also an inflammatory disease it may cause when activated accidentally, in the absence of infection. We are also investigating pathways that keep this inflammation in check, and how pathogens might hijack these anti-inflammatory pathways to promote infection.Read moreRead less
Immune Regulation Of Colitis And Associated Cancer
Funder
National Health and Medical Research Council
Funding Amount
$646,995.00
Summary
Inflammatory bowel disease is a debilitating condition that can significantly increase the likelihood of developing colon cancer. There are many different cellular pathways that lead to this inflammation, but we have uncovered a key signal that can prevent it from occurring. Specifically, we have identified how this signal increases a new type of suppressive cell that fights inflammation in the colon and can also stop this leading cancer.
As the first recruited cells, neutrophils direct protective responses against infection, but can also mediate destructive responses in inflammatory disease. This project will determine mechanisms driving neutrophil-dependent inflammation in both settings, by examining a specific inflammation-promoting molecular pathway (the ïinflammasomeÍ) in neutrophils. This research will lead to a better understanding of inflammation, and may suggest therapeutics for treating inflammatory disease.