Improving Treatment Strategies For Chronic Alphaviral Arthritic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$643,624.00
Summary
Chikungunya virus and Ross River virus cause epidemics of acute and chronic arthritic disease in humans, which is often poorly managed with current treatments. This grant seeks to understand the mechanisms that give rise to disease in order to identify improved treatment strategies. Both the persistence of viral replication in joint tissues and unnecessary inflammatory responses appear to be important factors driving chronic disease.
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.
HLA-G/H2-Bl Is Critical For Regulating Inflammation In The Liver
Funder
National Health and Medical Research Council
Funding Amount
$494,050.00
Summary
The key factor to induction of liver fibrosis, progression to cirrhosis, and hepatocellular carcinoma is inflammation. Liver transplant and liver regeneration following liver resection are also dramatically impaired by elevation of inflammation. We have identified a potent anti-inflammatory protein, HLA-G, that is critical for regulating post-surgical inflammation in the liver. We will determine if HLA-G can reverse and/or block liver fibrosis and modify HLA-G for improved clinical potential.
Strain-level Characterisation And Visualisation Of The Mucosal Microbial Communities Associated With Inflammatory Bowel Disease (IBD) For The Development Of Novel Biotherapeutics
Funder
National Health and Medical Research Council
Funding Amount
$1,181,878.00
Summary
Australia has one of the highest incidence rates in the world of Inflammatory Bowel Disease (IBD), a debilitating inflammatory condition of the gastrointestinal tract. Cutting-edge molecular and visualisation technologies will be used to examine the role of the gut microbiome in IBD, and identify specific members of this community to be used as new therapies to suppress inflammation and improve outcomes for patients with IBD.
Recycling Endosomes Governing Cell Polarity And Cytokine Secretion.
Funder
National Health and Medical Research Council
Funding Amount
$958,412.00
Summary
Cytokines are chemical messengers released by cells to mount inflammatory responses to fight infections. The timing and direction of cytokine release must be tightly regulated. We investigate the cellular compartments and molecules that control cytokine secretion using sophisticated live cell imaging. Uncontrolled cytokine release is the main cause of ongoing inflammation in arthritis and inflammatory bowel disease and our studies aim to identify cellular targets for new drug development.
Regulating The Secretion Of Inflammatory Cytokines
Funder
National Health and Medical Research Council
Funding Amount
$558,441.00
Summary
Cytokines or chemical messengers released by cells are essential for controlling immune responses but, in excess, they cause Crohn's disease and arthritis. Our research aims to block cytokine release as a novel way to ameliorate disease. We have identified specific cellular proteins, called golgins, that can be targeted to reduce cytokines. Here, characterization of golgin mediated cytokine transport in cells and in a mouse disease model is necessary to translate these findings for human benefit
Role Of Tissue Ferritin As A Proinflammatory Mediator Of Hepatic Stellate Cell Activation In Hepatic Iron Overload.
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
The hepatic stellate cell is responsible for liver scarring (fibrosis) in chronic liver diseases such as the iron overload condition Haemochromatosis. Our research has identified a role for tissue-derived ferritin as a proinflammatory cytokine in hepatic stellate cell biology. This proposal will examine the mechanisms associated with ferritin's proinflammatory action and assess its role in the fibrosis which occurs in Haemochromatosis.
The role of the immune system in pain is emerging from recent discoveries, and may hold the key to novel pain treatments. Most people experience brief gut infections from food or contagion without long-term consequences. Many others suffer symptoms for years afterwards - probably the best example of immune-based pain. Our project investigates how immune cells communicate with sensory nerves, and how these communications change from both angles after gut infection or inflammation.
Transient Receptor Potential Channels (TRPs) As Transducers And Targets In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$669,130.00
Summary
Transient receptor potential, or TRP channels, are involved in generating many of the sensations we perceive, such as heat, cold, touch and pain. Some TRP channels are specialized to signal pain from visceral organs, which we must investigate if we are to find treatments for visceral pain, which are currently lacking.
Macrophages are white blood cells that provide front line defence against infection by initiating inflammatory responses by ingesting or phagocytosing microbes and by releasing soluble messengers (cytokines) to recruit other immune cells. These defensive functions require extensive trafficking of proteins within the macrophages. Protein trafficking is orchestrated in part by a family of membrane fusion proteins called SNAREs. By defining the relevant SNAREs, we have recently discovered a much ac ....Macrophages are white blood cells that provide front line defence against infection by initiating inflammatory responses by ingesting or phagocytosing microbes and by releasing soluble messengers (cytokines) to recruit other immune cells. These defensive functions require extensive trafficking of proteins within the macrophages. Protein trafficking is orchestrated in part by a family of membrane fusion proteins called SNAREs. By defining the relevant SNAREs, we have recently discovered a much acclaimed and novel pathway that allows efficient, combined cytokine secretion and phagocytosis in macrophages. Our studies proposed here will now expand on this discovery by comparing the phagocytic process, in terms of SNARE-mediated membrane and cytokine trafficking, for a wide range of microbes, highlighting differences that could provide new avenues for drug development. Moreover, since our strategy of using SNAREs to investigate and map trafficking pathways has proven so successful, we will now launch a major large-scale initiative to study ALL SNARE-mediated trafficking pathways in macrophages using a discovery pipeline of assays, including live cell imaging, we have developed. This will provide valuable information on many SNAREs including those associated with disease, and will elucidate trafficking pathways governing all macrophage actions in immunity, including cytokine secretion and antigen presentation. All of these pathways are highly relevant to current drug targets being used clinically or studied in inflammatory disease and for the development of vaccines.Read moreRead less