Role Of Inflammation In The Physiological And Pathological Function Of The Gastrointestinal Tract
Funder
National Health and Medical Research Council
Funding Amount
$443,946.00
Summary
The gastrointestinal tract is continuously exposed to the external environment as a consequence of what we ingest. We have therefore evolved distinct mechanisms to deal with exposure to non-pathogenic insults in the gut. Sometimes, however these mechanisms fail leading to chronic inflammation and resultant pathology, which can under certain circumstances develop into cancer. This study will investigate inflammation in the gut, with particular interest in the systems that control inflammation.
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.
Inflammatory Bowel Disease (IBD) has two clinical forms known as Ulcerative Colitis (UC) and Crohn's Disease (CD). These are severe diseases which predominantly affect young people. They are occasionally fatal and often severely debilitating. Treatment of UC frequently requires removal of the large bowel and life long wearing of an ileostomy bag. While this is curative, its psychological and life style effects are very disturbing particularly in the young. The cause of IBD is unknown, although i ....Inflammatory Bowel Disease (IBD) has two clinical forms known as Ulcerative Colitis (UC) and Crohn's Disease (CD). These are severe diseases which predominantly affect young people. They are occasionally fatal and often severely debilitating. Treatment of UC frequently requires removal of the large bowel and life long wearing of an ileostomy bag. While this is curative, its psychological and life style effects are very disturbing particularly in the young. The cause of IBD is unknown, although it is clear that there are both genetic and environmental factors. We have developed a model of IBD in mice which appears to be very like human UC. We have generated genetically modified mice in which it appears that the mucous secreted by their bowel wall is different from normal. We propose to investigate how this change leads to UC. It appears likely that the mucous is defective and can not prevent some of the normal bacteria or other material present in the stools from entering the bowel wall and causing chronic inflammation. If we can show that this is the case, it adds strong support to the the idea that a similar genetic trait may occur in some humans and that this may be one of the genetic components which renders them susceptible to IBD. Put another way, it would be a pointer to the type of genetic defect which may underlie susceptibility in humans and so help to focus the search for the genetic component. Understanding genetic factors underlying disease susceptibility is vitally important to inform genetic counselling. In addition, understanding the various factors which lead to IBD is critical to developing rational treatments which target cause rather than the symptoms of the disease.Read moreRead less
Understanding The Role Of Nociceptin In PMNL-mediated Inflammation In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$474,750.00
Summary
This work will study the role of a type of protein in white blood cell movement into tissues, a process called inflammation. The outcome of this work may lead to the development of molecules which control this movement of white blood cells more specifically than existing therapeutics. Such inhibitors would potentially be useful as anti-inflammatory agents in a range of human diseases.