Mechanism Of Proteotoxic Stress Induced Type I Interferon Signalling And Implications For Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$322,952.00
Summary
All cells have a proteasome system to degrade unwanted proteins. Proteasome dysfunction causes a build-up of proteins that triggers, through an unknown mechanism, activation of the immune system leading to inflammation. People with mutations in genes which code for proteasome activity experience a severe disease known as Proteasome-Associated Autoinflammatory Syndrome. We aim to elucidate the link between protein aggregation and immune activation and employ this knowledge in disease treatment.
Understanding The Role Of The IL11-Stat3-Th17 Signaling Axis In Gastrointestinal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$531,743.00
Summary
Gastrointestinal cancers arise when abnormal cells grow out from otherwise normal tissue. The resulting tumours contain a number of different types of cells, some of which help the tumour to grow, and some of which fight the tumour. We are interested in understanding how soluble molecules called cytokines influence the cells that promote tumour growth. In particular, we will explore the role of a cytokine called Interleukin-11 in these processes to identify novel cancer therapies.
Interferon Regulatory Factor 6: A Novel Epithelial-specific Regulator Of Mucosal Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$517,989.00
Summary
Epithelial cells lining the respiratory and gastrointestinal tracts play pivotal roles in protecting us from infection. Inflammatory factors released by epithelial cells are important for fighting infection; however, they also contribute to chronic inflammatory diseases. We aim to understand how a protein called IRF6 regulates the inflammatory response of epithelial cells. The knowledge gained will identify new therapeutic approaches for inflammatory diseases.
After infection with viruses, parasites and bacteria the protein SerpinB2 becomes very abundant in macrophages, which are white blood cells involved in inflammation. Unfortunately, what this protein is doing is very unclear. We have found that macrophage SerpinB2 dampens the responses of other immune cells. This grant aims to determine how this is achieved and thereby help resolve the role of this protein in a number of diseases such as cancer, lupus, asthma and pre-eclampsia.
This project aims to comprehensively evaluate the role of androgen receptor (AR) signalling in breast cancer by identifying changes in AR signalling and its role in an endocrine resistant setting. Understanding the changes in AR signalling in either treatment-naive or treatment-resistant context would better assist in the identification for opportunities to modulate AR signalling as a therapeutic target in breast cancer.
The pathology of many acute and chronic diseases associated with the inappropriate activation of genetically encoded programmed cell death pathways, such as sepsis, stroke, diabetes and neurodegeneration, is linked to detrimental inflammation. This project will accurately define at the molecular level how programmed cell death triggers inflammatory responses, and use this knowledge to test novel and next-generation therapeutic strategies in inflammatory-driven diseases.
Interleukin-1β Biology: Mechanisms Of Regulation, Activation And Secretion
Funder
National Health and Medical Research Council
Funding Amount
$641,979.00
Summary
The protein called intelreukin-1 (IL-1) is required to fight off invading pathogens but more recently has been implicated as contributing to diverse diseases characterised by excessive inflammation, such as arthritis, gout, atherosclerosis and even cancer. This project aims to understand how IL-1 is made within cells and then activated to cause inflammation, which will enable these processes to be therapeutically targeted.
Integrating Wnt-Apc Pathway With TGF-beta Signalling In Colon Cancer
Funder
National Health and Medical Research Council
Funding Amount
$342,364.00
Summary
Colon cancer is one of the leading causes of death of all cancers. Two molecular pathways have been independently implicated in colon cancer development. Emerging evidences suggest that the two pathways may work together in the colon polypus formation. This application will integrate two separate molecular causes to form a new coherent understanding of cancer development and offer new directions in development of novel colon cancer treatment.
Molecular Dissection Of Aberrant IL6/gp130 And TGF? Signaling In The Pathogenesis Of Interstitial Pneumonitis
Funder
National Health and Medical Research Council
Funding Amount
$590,009.00
Summary
Interstitial pneumonia (IP) is frequently observed in the group of lung diseases which affect the transfer of oxygen from inhaled air into the bloodstream. Current treatments for these diseases only effectively manage patient’s symptoms but don’t cure patients of IP. We have developed a strategy to identify the exact cell type responsible for an acute IP and the molecular intermediates that may offer novel treatments and pave the way for a possible cure for this disease.
Molecular Targeting Of Innate Immune Signalling Pathways In Cancer And Auto-Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$753,300.00
Summary
To achieve an accurate molecular understanding of innate immune system receptor signalling, both intracellularly and in whole organisms, in health and disease. This knowledge will then be used to generate better treatments for the extensive range of human diseases that are caused or exacerbated by dysfunctional innate immune signalling, including Crohn's disease, psoriasis and cancer.