Functional Dyspepsia: Characterisation Of The Immunopathology And Testing A Novel Therapeutic Strategy.
Funder
National Health and Medical Research Council
Funding Amount
$739,604.00
Summary
Dyspepsia, unexplained stomach discomfort and pain, is a common and costly problem; few effective treatments exist and the causes are unknown. We have found that the numbers of a type of immune cell, the eosinophil, are increased in the top of the small bowel in patients with dyspepsia. This study will explore the mechanisms that lead to increased eosinophils and then test the effectiveness of a treatment to suppress this overactive immune response which could rapidly change clinical practice.
Defining The Role Of MMP-9-expressing Macrophages In Liver Injury In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$542,028.00
Summary
Defining pathways that lead to fibrosis in chronic liver disease is an urgent priority and unmet need because cirrhosis remains a major cause of death. We will study the development of an additional fibrogenic pathway involving altered liver repair mechanisms, in order to seek ways to restore liver function. New insights arising from this novel research could significantly advance our understanding of how fibrosis develops and lead to new approaches to treat and prevent advanced liver disease.
Exploring The Mechanisms Of Generation Of Intestinal TH17 Responses And The Mechanisms Of TH17 Mediated Pathology
Funder
National Health and Medical Research Council
Funding Amount
$617,531.00
Summary
Our research recently described a mouse that shows excellent similarities to human inflammatory bowel diseases. We further show that the disease mediating substances called cytokines are also similar between our mouse and UC. Particularly, a recently described network of cytokines that are the major mediators of disease in our mice and human IBD. This project examines how we can best interfere with the actions of these cytokines to treat and prevent intestinal inflammation.
Studies On The Pathogenesis And Treatment Outcomes Of Chronic Viral Hepatitis
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
The global impact of hepatitis B and hepatitis C has recently been recognized by the World Health Organization. The Fellowship will support a research program that will use new technologies to answer a number of important questions concerning the pathogenesis of viral hepatitis B and C, interferon treatment response for HCV, and antiviral drug resistance. The outcomes of the research will be timely, clinically relevant, and of great interest to the international community. The ultimate goal is t ....The global impact of hepatitis B and hepatitis C has recently been recognized by the World Health Organization. The Fellowship will support a research program that will use new technologies to answer a number of important questions concerning the pathogenesis of viral hepatitis B and C, interferon treatment response for HCV, and antiviral drug resistance. The outcomes of the research will be timely, clinically relevant, and of great interest to the international community. The ultimate goal is to improve clinical outcomes for patients.Read moreRead less
Hepatitis C affects a quarter of a million Australians, causing insidious but progressive liver disease which culminates in liver failure or cancer. There is no vaccine and prevention programs have limited effectiveness, but new antiviral therapies now offer high rates of cure. This Program will evaluate strategies to improve the health of those affected and prevent new infections by better understanding of the virus and the body’s immune response, including scarring and liver cancer formation.
Appendicitis, Protection Again Colitis And The Role Of Colonic Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$67,381.00
Summary
The appendix has been regarded as a useless organ, however, there are evidence showing its removal reduces the risk of developing inflammatory bowel disease. We have shown that this may be due to altered intestinal immune regulation. The project plans to explore the mechanisms responsible for this altered immune regulation. With knowledge of specific elements of disease causation gained from these studies, more effective and targeted treatment options will become available.
The Appendix In Intestinal Immunity And Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$465,210.00
Summary
Inflammatory bowel diseases (IBD) consist of two entities: ulcerative colitis and Crohn's disease. IBD causes relapsing and remitting gut inflammation in relatively young populations of patients. Our understanding of causes of IBD is poor, but the diseases involve an interaction between the intestinal immune system, genetic predisposition and bacteria in the gut. One unexplained observation, made by a number of groups, is that removal of the appendix, especially if performed when young, protects ....Inflammatory bowel diseases (IBD) consist of two entities: ulcerative colitis and Crohn's disease. IBD causes relapsing and remitting gut inflammation in relatively young populations of patients. Our understanding of causes of IBD is poor, but the diseases involve an interaction between the intestinal immune system, genetic predisposition and bacteria in the gut. One unexplained observation, made by a number of groups, is that removal of the appendix, especially if performed when young, protects against the later development of ulcerative colitis and probably Crohn s disease. If IBD does develop following earlier appendicectomy, it tends to be less severe. In this project, we plan to examine the immune features of the appendix, in human and mouse. The appendix is a major source of immune cells in the intestine but the nature of these cells and their functions are poorly understood. The aims of the project will explore the nature of immune cells, known as T lymphocytes, isolated from human and mouse appendices. Changes with age will be examined, to explain the age-related nature of the appendicectomy-IBD link. Anti- and pro-inflammatory characteristics of the cells will be studied, the migration pathways of these cells from appendix to other parts of the intestine will be clarified, and the therapeutic potential of these T cells in a mouse model of IBD will be elucidated. In addition, this will be the first study to develop and analyse a mouse model of appendicitis, which is very poorly understood. These studies will make important observations relevant not only to IBD, but to the immune function of the intestine, with implications for our fundamental understanding of the way we are protected from our hostile environment.Read moreRead less
Epithelial cell surface mucins are large complex proteins found on the surface of all mucosal epithelial tissues, for example in the respiratory, gastrointestinal, reproductive and urinary tracts. Most bacterial and viral pathogens enter the body via mucosal tissues. We have recently demonstrated that mucin proteins are a vital component of initial defence against mucosal pathogens. Defects in these proteins probably predispose individuals to common chronic infective and inflammatory diseases. T ....Epithelial cell surface mucins are large complex proteins found on the surface of all mucosal epithelial tissues, for example in the respiratory, gastrointestinal, reproductive and urinary tracts. Most bacterial and viral pathogens enter the body via mucosal tissues. We have recently demonstrated that mucin proteins are a vital component of initial defence against mucosal pathogens. Defects in these proteins probably predispose individuals to common chronic infective and inflammatory diseases. The proposed research aims to explore the mechanims by which mucins protect from infection, with a focus on the gastrointestinal tract. Gastrointestinal infections remain one of the major causes of mortality in children in undeveloped countries. We believe that these proteins are a critical hereto unrecognised element of immunity and that the proposed studies will have broad significance for treatment and prevention of infection. Additionally, understanding the function of mucins could lead to the development of new drugs to treat epithelial inflammation such as that seen in inflammatory bowel diseases and respiratory diseases such as asthma and cystic fibrosis.Read moreRead less