Muc1 Regulation Of The NLRP3 Inflammasome In The Gastrointestinal Tract
Funder
National Health and Medical Research Council
Funding Amount
$444,351.00
Summary
The mucin Muc1 is an important part of the barrier against infection in the gut, and appears to protect against development of bacterial inflammatory disease. We have identified that Muc1 suppresses activation of the inflammasome (a mechanism by which pathogens cause inflammation). We will now examine how Muc1 does this and explore the importance of this effect on inflammatory disease in the intestine. This may identify novel approaches for protecting against gastric and colorectal cancer.
Cell Surface Mucins In Gastrointestinal Infection, Inflammation And Cancer Development
Funder
National Health and Medical Research Council
Funding Amount
$469,627.00
Summary
Cell surface mucins are protective molecules that line all the wet surface of the body, including the gastrointestinal tract. Our research has uncovered that mucins regulate cell growth and cell death. Inappropriate control by the mucins, could lead to chronic inflammation and formation of cancers. We will test how important these molecules are in the development of cancers in the intestine, and further explore the mechanism of action.
ASSESSMENT OF ENDOPLASMIC RETICULUM STRESS AND MUTATIONS IN MUCIN OLIGOMERIZATION DOMAINS IN ULCERATIVE COLITIS
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
Ulcerative colitis affects 0.2% of Australians causing chronic or recurrent health morbidity and affecting employment. In severe cases it is life threatening. Its pathogenesis remains poorly understood. We have exciting and novel preliminary data from humans and informed by our unique animal models that make us propose that the disease is caused by Endoplasmic Reticulum Stress due to misfolding of mucin. We have designed fully powered prospective clinical and lab studies to test this hypothesis.
Investigating The Effects Of Macrolides On Excessive Synthesis And Secretion Of Airway Mucins Using Novel Ex Vivo And In Vivo Approaches
Funder
National Health and Medical Research Council
Funding Amount
$520,821.00
Summary
Many people have difficulty breathing because the airway tubes that move air in and out of their lungs are blocked by excessive amounts of sticky mucus. Our project will use new techniques developed in our laboratories to investigate whether a group of medicines called “macrolides” can prevent the excessive production and release of mucus in the airways, and thus be beneficial in treating asthma, and potentially other lung diseases.
Disrupting Mucin-mucin Interactions To Treat Respiratory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$480,531.00
Summary
Diseases like asthma, emphysema and cystic fibrosis all feature the overproduction of mucus in the lungs that make it very difficult for patients to breathe and increases their susceptibility to infections. Few therapies are available for thinning this mucus, which is made thick by a network of linkages between proteins. We are studying these linkages and developing methods to break them up. This research could yield new mucus-thinning drugs to treat lung diseases.
Faecal Microbiota Transplantation And Other Novel Therapeutic Microbial Manipulation Strategies In Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
There is growing interest in the role of microbial-based strategies including faecal microbiota transplantation (FMT) for the treatment of inflammatory bowel disease. This project will develop such strategies into valid treatment options through a combination of clinical & basic science work including (1) characterising viral & fungal factors of importance, (2) evaluation of novel orally-delivered formulations of FMT, and (3) development of better defined, more reproducible microbial treatments.
Integrated Clinical And Scientific Studies In Post-Operative Crohn’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$71,606.00
Summary
Crohn’s disease is a chronic inflammatory bowel condition; the incidence in Australia is now amongst the highest in the world. Most patients require repeated invasive bowel surgeries when disease recurs. Using data from a past clinical trial comparing preventive treatments for recurrence; genetic, immunological and microbiological testing will be done on existing patient samples. This extensive data set will be analysed using systems biology methods to identify the cause of Crohn’s disease.