Novel Applications Of Ghrelin Peptides In Mouse Models Of Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$243,116.00
Summary
Inflammatory bowel disease (IBD) is a debilitating, chronic condition that often affects patients in the primes of their lives. A limited number of treatments are currently available for these patients and those that are available often have serious side effects, including growth restriction in children. Ghrelin is a natural hormone that has been shown to suppress many features of IBD. This project will investigate the potential of ghrelin as a new treatment for inflammatory bowel disease.
Molecular & Translational Characterisation Of IMiD-Mediated BET-Protein Degradation In Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$497,857.00
Summary
Thalidomide-like drugs (called IMiDs) are an essential treatment for multiple myeloma, a common incurable blood cancer. We have discovered that IMiDs destroy proteins that myeloma cells use to ‘read’ cancer-causing genes in their own DNA. We will therefore investigate how important the destruction of these ‘gene readers’ is in myeloma cells, including patient samples. This will set up future studies targeting ‘gene readers’ using IMiDs in combination with other targeted drugs in clinical trials.
Building A Bridge Between Animal Models Of Blood Transfusion And Clinical Practice: Development Of Sheep Laboratory Models To Investigate The Effects Of Transfusion
Funder
National Health and Medical Research Council
Funding Amount
$86,117.00
Summary
This research project aims to develop clinically-relevant sheep laboratory models of transfusion that will provide a ‘bridge’ between human laboratory and sheep in vivo models and clinical setting by contributing to a better understanding of the underlying mechanisms of transfusion with stored blood products. Ultimately, addressing key knowledge gaps regarding transfusion of aged and cryopreserved blood products will result in improved outcomes for patients.
Mechanisms Of Action Of The Trefoil Peptides In Promoting Healing In Models Of Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$365,270.00
Summary
Preliminary experiments from our laboratory have shown that members of a family of small proteins called trefoil peptides, found naturally in the stomach, intestine and colon, are able to shorten the healing time of ulcers and reduce inflammation, in an animal model of inflammatory bowel disease. Crohn's disease and ulcerative colitis together make up the human inflammatory bowel diseases, or IBD for short. They afflict many members of the community, are debilitating, expensive to treat, and cur ....Preliminary experiments from our laboratory have shown that members of a family of small proteins called trefoil peptides, found naturally in the stomach, intestine and colon, are able to shorten the healing time of ulcers and reduce inflammation, in an animal model of inflammatory bowel disease. Crohn's disease and ulcerative colitis together make up the human inflammatory bowel diseases, or IBD for short. They afflict many members of the community, are debilitating, expensive to treat, and current treatments like corticosteroids and suppressors of the immune system have unpleasant and health-threatening side effects. There are therefore good reasons for the development of new forms of therapy which will be better tolerated and which are specific in their actions. We believe that the trefoil peptides may be good candidates on which new treatments for inflammatory disease might be based. The studies outlined in this proposal will test the best route of administration, and how often to give trefoil peptides in order to relieve the symptoms of experimental IBD. In addition the effectiveness of the trefoils will be compared to other agents currently used in IBD treatment, or which are known to relieve inflammation or speed the healing of the ulcerated colon. We will also carry out experiments designed to work out the mechanisms by which the trefoils' healing effects are mediated, and finally we will characterise a new member of the trefoil peptide family which we have recently discovered.Read moreRead less
Genomic Medicine: Predictors Of Refractory Ulcerative Colitis And Its Response To Treatment
Funder
National Health and Medical Research Council
Funding Amount
$879,048.00
Summary
Ulcerative colitis (UC) is a major form of inflammatory bowel disease, affecting over 35,000 Australians. Symptoms include bleeding from the anus, tummy pain, and diarrhoea. There is a 1 in 4 risk of needing major surgery for UC. Our study will use current genetic techniques to classify patients according to the severity of their colitis, and their response to treatments. This will allow clinicians to personalize medical treatment far more effectively from the outset of a patients’ disease.
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
Immunotherapy has recently shown promise in bone cancer. We have found that while immune modulators Il-6 and Ifn?? contribute to tumour suppression Il-23 promotes the growth of radiation-induced bone cancer. We have generated mouse models of bone cancer to investigate tumour growth and immune surveillance in immune competent mice with an overall aim of identifying therapeutic targets in this disease.