Regulation Of NOD Signalling By IAPs And RIP Kinases
Funder
National Health and Medical Research Council
Funding Amount
$643,172.00
Summary
Alterations in NOD signalling have been implicated in various human inflammatory diseases, particularly in Crohn’s disease and asthma. In this project we will identify new molecules that regulate NOD signalling and test the effect of drugs that inhibit known components of these pathways to determine their utility in treating inflammatory diseases.
Inflammatory skin disorders, such as psoriasis and dermatitis, are responsible for a large burden of human disease and affect people across alldemographics. Knockout (KO) of TNF signalling members in mice is known to induce skin inflammation. This project proposes to use these genetic mouse models to investigate how and why disruption of particular TNF superfamily members leads to disease and potentially identify new targets for treatment.
How Does Inflammation Of The Gut Change Its Sensory Innervation?
Funder
National Health and Medical Research Council
Funding Amount
$613,767.00
Summary
A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for th ....A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for this type of symptom. It is becoming apparent that a large subgroup of IBS patients have undergone prior infection or inflammation, and that there are in fact changes in the types of cells in biopsies from their gut. Thus there are common features to IBS and inflammation. These may provide a means for us to find new treatments for IBS and IBD symptoms. Mice develop similar microscopic changes in the colon after experimental inflammation to those seen in humans, so we can discover more from this model. We have recently established that there are several types of sensory nerve fibres from the mouse colon and rectum that convey information about contractions, distension and chemical mediators released from tissue to the central nervous system. These are almost certainly responsible for generating symptoms in patients. We aim in this project to discover how these sensory nerves change in their responsiveness to mechanical and chemical stimuli in experimental inflammation. Importantly we shall investigate the mediators that are present in the tissue which may activate sensory nerves and-or the receptors on sensory nerves that may be increased. These experiments we hope will provide a target at which to aim novel drug treatments for symptoms of IBS and IBD.Read moreRead less
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.
Deadly Commute - Targeting The Trafficking Mechanisms That Licence Inflammatory Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$774,544.00
Summary
MLKL is a protein naturally found inside cells. MLKL is activated by inflammation. Once activated, MLKL relocates to the outer periphery of cells and kills them. Gut cells are especially vulnerable to death-by-MLKL and this problem causes Inflammatory Bowel Disease. Using cutting edge microscopy, we have discovered how MLKL moves to the periphery of cells prior to killing them. We will test if blocking this movement of MLKL to the cell periphery stops gut death and Inflammatory Bowel Disease.
Host Cell Death Signaling And Susceptibility To Bacterial Gut Infection
Funder
National Health and Medical Research Council
Funding Amount
$682,321.00
Summary
Bacterial infections are a major cause of infectious disease worldwide. Here we aim to characterise immune responses that help fight infection by E. coli and Salmonella. These bacteria have evolved ways to shut down many of our immune responses during infection, allowing them to survive and cause disease. This work will help understand the complex relationship between gut bacteria and our immune system and provide solutions for controlling infection and treating immune disorders of the gut.
Prevention Of Beta Cell Destruction In Type 1 Diabetes By Immunotherapy Using Parasite-derived Molecules.
Funder
National Health and Medical Research Council
Funding Amount
$518,443.00
Summary
To prevent type 1 diabetes, compounds that avert the autoimmune destruction of beta cells are needed. We are exploiting the potential of ñworm therapyî by mimicking the beneficial immune effects of parasite worm infection. We have identified the molecules that the parasite uses to influence host immune responses. We have demonstrated that these novel immune-modulatory worm molecules prevent diabetes in a mouse model. This offers great potential for the development of therapeutic interventions.
Chronic inflammation underlies common and debilitating diseases and causes pain by unknown mechanisms. There is an urgent need to gain a deeper understanding of the mechanisms of chronic pain, which will allow the development of improved therapies with fewer side-effects. Our research program investigates the mechanisms of pain that are associated with inflammatory bowel disease and irritable bowel syndrome, with the goal of developing more effective and selective therapies.
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.
Neuroimmune Interactions In Functional And Organic Gastrointestinal Diseases
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) are chronic, incurable diseases of the lower gastrointestinal tract with unknown causes and poor treatment options. Both the immune and nervous systems are altered in GI disease, but have traditionally been studied in isolation. My research investigates how the neuro-immune axis is altered in these diseases, using animal models and human tissue samples to identify novel treatment options for these debilitating diseases.