Cell Surface Mucins In Gastrointestinal Mucosal Innate Immunity
Funder
National Health and Medical Research Council
Funding Amount
$475,500.00
Summary
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. We have recently identified three of the seven genes currently known to produce this type of molecule. We propose that mucins have a very important role in maintaining the barrier between potentially infectious microorganisms often present in epithelial tracts and the internal organs. We also believe 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. We have recently identified three of the seven genes currently known to produce this type of molecule. We propose that mucins have a very important role in maintaining the barrier between potentially infectious microorganisms often present in epithelial tracts and the internal organs. We also believe that these molecules trigger epithelial cell defensive responses to the presence of microorganisms. The proposed research aims to prove these propositions and to elucidate the molecular mechanisms underlying function of cell surface mucins. Understanding the function of cell surface 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
Cell Surface Mucins In Gastrointestinal Infection And Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$591,967.00
Summary
Mucosal tissues, such as the gastrointestinal and respiratory tracts, are the most common site of infectious disease. We have found that the cells in these tissues produce molecules on their surface, known as mucins, that protect from infection. In the case of chronic infection the mucins prevent the inflammation that underlies the development of cancer. In this project we will be exploring the mechanisms by which mucins prevent infection and inflammation.
My basic science and translational research centres around elucidation of the function of the mucosal barrier in preventing infection, inflammation and development of cancers, and how defects in this barrier lead to these diseases.
Immune Regulation, Cellular Trafficking And Chemokine Receptors In Intestinal Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$204,750.00
Summary
The intestine is exposed to a vast array of foreign substances, or antigens, from food to the abundant bacteria that populate the gut. The gut immune system has developed elaborate and poorly understood mechanisms for preventing inflammation in response to these antigens. A breakdown in these control mechanisms may be partly responsible for the chronic intestinal diseases known as inflammatory bowel diseases, which cause abdominal pain, diarrhoea and bleeding. A recently described immune cell ty ....The intestine is exposed to a vast array of foreign substances, or antigens, from food to the abundant bacteria that populate the gut. The gut immune system has developed elaborate and poorly understood mechanisms for preventing inflammation in response to these antigens. A breakdown in these control mechanisms may be partly responsible for the chronic intestinal diseases known as inflammatory bowel diseases, which cause abdominal pain, diarrhoea and bleeding. A recently described immune cell type, known as a regulatory T cell (T reg), is a powerful candidate cell as a master controller of intestinal inflammation. We know that T cells move to various sites in the body under the influence of hormone-like proteins known as chemokines, but the existence of T reg cells in the intestine, their characteristics, their behaviour and their specific response to chemokines, are all unknown. These studies aim to examine the presence and nature of T reg cells in human and mouse intestine, in both health and inflammation, and to explore how these cells migrate into the gut under the influence of chemokines. This knowledge will help in our understanding of intestinal immunity and endogenous regulation of immune responses, and will provide new targets for treatment of inflammatory bowel disease, and potentially other inflammatory diseases.Read moreRead less
Factors Controlling Leucocyte Migration In Healthy Intestine And In Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$195,217.00
Summary
Inflammatory bowel diseases (IBD) are relapsing and remitting disorders of the intestine that create substantial disability in a relatively young population of patients. Our treatments for these conditions have changed little in the last 30 years and they are commonly accompanied by side effects. Research into the mechanisms controlling the gut inflammation offers promise for the development of novel, targeted and less toxic therapies. The major mediators of damage in IBD are white blood cells r ....Inflammatory bowel diseases (IBD) are relapsing and remitting disorders of the intestine that create substantial disability in a relatively young population of patients. Our treatments for these conditions have changed little in the last 30 years and they are commonly accompanied by side effects. Research into the mechanisms controlling the gut inflammation offers promise for the development of novel, targeted and less toxic therapies. The major mediators of damage in IBD are white blood cells recruited from the circulation to affected intestine. This recruitment is induced by the production in damaged intestine of chemokines, proteins of the immune system that attract and activate white blood cells. Chemokines act through chemokine receptors on the surface of white blood cells, and earlier research by our group has demonstrated that these chemokine receptors can be functionally modulated by neuropeptides, proteins unrelated to chemokines that normally transmit messages within the nervous system. This project aims to explore the chemokines and chemokine receptors responsible for the recruitment of white blood cells to normal and IBD-affected intestine, in order to determine therapeutic targets for novel treatments. Moreover, the role of neuropeptides in modulating the recruitment of white blood cells to the intestine will be examined in cells from the human intestine, both normal and IBD-affected, as well as in an animal model of IBD. This project will provide an understanding of the signals responsible for the attraction of damaging white blood cells to sites of inflammation in the bowel and will indicate mechanisms used by the immune system to regulate those signals. It has the potential to direct us to new therapies that use highly targeted and physiologically appropriate approaches to controlling white blood cell trafficking in health and disease.Read moreRead less
POST-OPERATIVE CROHNS DISEASE RECURRENCE: EVALUATION OF AETIOLOGIC FACTORS And AN ALGORITHM And TRIAL TO MODIFY RECURRENCE.
Funder
National Health and Medical Research Council
Funding Amount
$123,472.00
Summary
Eighty percent of patients with Crohn’s disease (CD) need an operation at some stage. The disease invariably returns, and in 70% of patients further surgery is required. This project aims to determine whether particular bacteria cause the disease to recur and will look at the value of antibiotic treatment to prevent severe disease recurring. It will also assess whether adjusting treatment based on changes seen at the operative site during follow-up influences disease recurrence .
Crohn's disease is a severe, chronic inflammatory disease of the gut which affects up to 50,000 Australians. The majority of patients develop the disease in their twenties, with significant impact on their quality of life. Our preliminary work has identified a novel gene, which could potentially cause a critical reduction in the production of anti-bacterial proteins by cells in the small bowel. Exploring the function of this gene in relation to clinical outcome could lead to better treatment.
The Role Of Capsulin, A New BasicHelix-Loop-Helix Factor, In Differentiation And Repair Of The Gastric Mucosa.
Funder
National Health and Medical Research Council
Funding Amount
$131,812.00
Summary
We aim to understand the role that a new factor plays in the processes whereby the lining of the stomach is continually renewed, and also repaired after injury due to inflammation and ulceration. Once we understand the role of this factor and how it works, we may be able to use this factor as a therapeutic to prevent the initial formation of inflammation and ulceration in the stomach that can lead to more serious diseases, such as cancer.