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.
Acute Severe Ulcerative Colitis - Clinical And Translational Studies
Funder
National Health and Medical Research Council
Funding Amount
$340,891.00
Summary
One in five patients with severe ulcerative colitis, a condition resulting in damage to the large bowel, may require surgery to remove the bowel. This project aims to find out how best to avoid surgery using a drug called infliximab which targets the immune system to reduce bowel damage. This study also aims to find changes in the immune system that cause ulcerative colitis and identify which patients are more likely to avoid surgery with infliximab thereby minimising side effects and costs.
A Role For Double-stranded RNA-dependent Protein Kinase In Regulating Nod-like Receptor Signaling For Modulating Colitis And Colitis-associated Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$230,600.00
Summary
Inflammatory bowel disease (IBD) and Colorectal cancers (CRC) are commonly found in developed countries like Australia. In spite of improved treatment for IBD and CRC, it is still not known why many patients are still not responsive to these therapies. Therefore, this proposed project aims to use genetically modified mice and molecular biology techniques to understand the pathogenesis of these diseases and to find an alternative new treatment for these diseases.