Regulator Of G Protein Signalling-5 Loss And Gain Of Function In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$625,428.00
Summary
Cancer and cardiovascular diseases are amongst the largest causes of morbidity and mortality in Western populations. We have identified a molecule, called Regulator of G protein signalling 5 (RGS5), which is involved in vessel remodelling in both diseases. This molecule is a prime candidate for drug development. We will study the precise role of RGS5 in sophisticated preclinical models which will create future opportunities for urgent therapy.
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.
Cancer causes significant morbidity and mortality in Australia’s aging population. There is strong evidence that abnormal blood vessels in tumours limit drug access and drive metastases. We have identified a molecule which controls vessel remodelling in tumours. In this proposal we will study mechanisms on how the molecule itself is regulated with the aim to normalize blood vessels for improved therapy.
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.
RGS5 Signalling In Cardiovascular And Smooth Muscle Cell Physiology
Funder
National Health and Medical Research Council
Funding Amount
$645,613.00
Summary
Cardiovascular diseases, including hypertension, remain one of the largest causes of morbidity and mortality in Western populations. We have identified a molecule, called Regulator of G protein signalling 5 (RGS5), which is involved in pathological vessel remodelling and in the regulation of blood pressure. This molecule is a prime candidate for drug development. We will study the precise role of RGS5 in cardiovascular disease models and regulatory pathways in cell systems.
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.
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.
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.