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.
Faecal Microbiota Transplantation For Active Ulcerative Colitis - A Randomised Controlled Trial: Clinical, Microbial & Immune Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$700,126.00
Summary
This is a placebo controlled clinical trial to see whether giving healthy donor faeces to people with active ulcerative colitis can get them into remission. We will also examine how long the donor microbiome stays in the recipients stool, and examine the effects of faecal transplantation on the immune response in the lining of the colon in recipients.
REMEDYING THE NEGLECT OF THE MOST COMMON COMPLICATION OF INFLAMMATORY BOWEL DISEASE: INTESTINAL STRICTURES.
Funder
National Health and Medical Research Council
Funding Amount
$123,368.00
Summary
Inflammatory bowel disease is a significant cause of debility in the Australian community. Some patients develop narrowing of the bowel which can cause intestinal blockages and require surgery. My research in this area will identify predictors of severe disease, allowing doctors to individualise treatment plans for each patient. I will also work to determine the best model of medical treatment and investigate new techniques which have the potential to avoid surgery.
C-myb Regulates Stem-progenitor Cell Cycle Entry In Colonic Crypts Providing Insights Into Colo-rectal Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$386,020.00
Summary
During a human's life time the colon or large bowel produced an extraordinary volume of cells. This requires almost unimaginable numbers of cell divisions. We are investigating the role of a gene (c-myb) that we propose is one of the key regulators of normal colon growth and function. It is expressed in the base of the functional unit of the colon called the colonic crypt. The base contains the stem cell population which give rise to all the crypt cells. We have generated and gathered a unique a ....During a human's life time the colon or large bowel produced an extraordinary volume of cells. This requires almost unimaginable numbers of cell divisions. We are investigating the role of a gene (c-myb) that we propose is one of the key regulators of normal colon growth and function. It is expressed in the base of the functional unit of the colon called the colonic crypt. The base contains the stem cell population which give rise to all the crypt cells. We have generated and gathered a unique and comprehensive set of mutant mice that have various degrees of dysfunction of the c-myb gene. We will study the colons of these mice to determine how c-myb regulates cell growth. We will also investigate these mice under stress conditions like that associated with cancer therapies like radiation treatment. Understanding such genes will improve the management of cancer patient how suffer gastro-intestinal side effects such as diarrhoea, perhaps hyper-proliferative disorders like inflammatory bowel disease and finally colon cancer where complete loss of cell growth is a feature.Read moreRead less
Stricture Definition And Treatment (STRIDENT) Studies: New Diagnostic And Treatment Modalities For Inflammatory Bowel Disease Strictures
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
Inflammatory bowel disease (IBD), which includes Crohn disease and Ulcerative colitis, is becoming increasingly common in Australia. IBD strictures, which are a narrowing of bowel wall as a result of inflammation, can cause obstruction or blockage of food and liquid contents in the bowel. This results in significant patient morbidity and disease burden. Our research will aim to characterise strictures in IBD and investigate novel medical treatments to significantly improve outcomes in IBD.
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
Clinical And Microbiological Studies Of Faecal Microbiota Transplantation In Ulcerative Colitis - A Phase II, Multicentre, Randomised Double Blind, Exploratory Proof Of Concept, Placebo Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$140,949.00
Summary
Ulcerative Colitis (UC) is a chronic inflammatory condition affecting the large bowel. It is the result of a dysfunctional immune system that inappropriately targets and damages the colon. There is increasing evidence that gut bacteria play a crucial role in UC, possibly by stimulating inappropriate activation of immune cells. We believe that by "transplanting" the faeces (and thus gut microbes) of healthy individuals into the colon of UC patients, we may change the bacterial make up and correct ....Ulcerative Colitis (UC) is a chronic inflammatory condition affecting the large bowel. It is the result of a dysfunctional immune system that inappropriately targets and damages the colon. There is increasing evidence that gut bacteria play a crucial role in UC, possibly by stimulating inappropriate activation of immune cells. We believe that by "transplanting" the faeces (and thus gut microbes) of healthy individuals into the colon of UC patients, we may change the bacterial make up and correct the inappropriate immune system activation.Read moreRead less
Bioresponsive Porous Silicon For Site Specific Oral Delivery Of Antibodies For The Treatment Of Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
This proposal aims to develop an oral antibody delivery system for treatment of inflammatory bowel disease (IBD) that affects 75000 Australians. The system will be based on porous silicon nanoparticles acting as a container to protect the antibodies, and bioresponsive coatings acting as gates to enable site specific protein delivery at the inflamed site of GI tract. The project not only holds promise for protein delivery for the treatment of IBD but other diseases like diabetes.