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Epithelial cell surface mucins are large complex proteins found on the surface of all mucosal epithelial tissues, for example in the respiratory, gastrointestinal, reproductive and urinary tracts. Most bacterial and viral pathogens enter the body via mucosal tissues. We have recently demonstrated that mucin proteins are a vital component of initial defence against mucosal pathogens. Defects in these proteins probably predispose individuals to common chronic infective and inflammatory diseases. T ....Epithelial cell surface mucins are large complex proteins found on the surface of all mucosal epithelial tissues, for example in the respiratory, gastrointestinal, reproductive and urinary tracts. Most bacterial and viral pathogens enter the body via mucosal tissues. We have recently demonstrated that mucin proteins are a vital component of initial defence against mucosal pathogens. Defects in these proteins probably predispose individuals to common chronic infective and inflammatory diseases. The proposed research aims to explore the mechanims by which mucins protect from infection, with a focus on the gastrointestinal tract. Gastrointestinal infections remain one of the major causes of mortality in children in undeveloped countries. We believe that these proteins are a critical hereto unrecognised element of immunity and that the proposed studies will have broad significance for treatment and prevention of infection. Additionally, understanding the function of mucins could lead to the development of new drugs to treat epithelial inflammation such as that seen in inflammatory bowel diseases and respiratory diseases such as asthma and cystic fibrosis.Read moreRead less
Vagal Nerve Stimulation As A Novel Therapy In Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$88,502.00
Summary
Inflammatory bowel disease (IBD) is common exerting a large personal and societal burden to the Australian population. Current medications used to treat IBD are expensive, have many side effects and at times require hospitalisation for their administration. We aim to develop the non invasive and inexpensive technique of vagal nerve stimulation as a novel treatment strategy for IBD.
Dissecting The TMPRSS6 Regulation Of Iron Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$613,311.00
Summary
Iron overload and anaemia are two of the most significant health problems affecting humans. Understanding how the body regulates iron levels is key to our understanding of these disorders and to the future development of new therapies. This research is aimed at understanding how a hormone produced in the liver called hepcidin that maintains iron balance is regulated. This research may lead to novel therapies aimed at correcting the iron balance in conditions of iron overload or anaemia
How Does Dietary Cholesterol Induce Non-alcoholic Steatohepatitis?
Funder
National Health and Medical Research Council
Funding Amount
$802,600.00
Summary
Non-alcoholic fatty liver disease is the most common liver disease that can progress to non-alcoholic steatohepatitis (NASH), cirrhosis and liver cancer. Dietary cholesterol is a major risk factor for NASH. We can demonstrate that cholesterol changes the gut bacteria. These bacteria generate toxic chemicals (bile acids) that signal to the liver and induce NASH. In this project, we use novel ways to clarify the mechanisms of liver inflammation and test novel therapeutic approaches to reverse it.
Epithelial - Stromal Interactions In Pancreatic Cancer: Role Of Pancreatic Stellate Cells
Funder
National Health and Medical Research Council
Funding Amount
$425,750.00
Summary
The pancreas is the major digestive organ in the body. It is located in the abdomen, draped across the spine behind the stomach. Pancreatic cancer is a leading cause of death in this country and in Western Society in general. Most patients with this disease survive only a few months after diagnosis. Even for those in whom a curative operation is undertaken, survival is poor. Chemotherapy and radiotherapy (alone and in combination) result in, at best, limited benefit. Clearly, there is a need for ....The pancreas is the major digestive organ in the body. It is located in the abdomen, draped across the spine behind the stomach. Pancreatic cancer is a leading cause of death in this country and in Western Society in general. Most patients with this disease survive only a few months after diagnosis. Even for those in whom a curative operation is undertaken, survival is poor. Chemotherapy and radiotherapy (alone and in combination) result in, at best, limited benefit. Clearly, there is a need for novel approaches to this lethal disease. The proposed project involves an examination of the local tissue reaction around pancreatic cancer. This tissue reaction is usually prominent and the cells involved may determine the extent of local and distant spread of the cancer. Modulation of this tissue reaction may limit pancreatic cancer growth and thus improve outcome.Read moreRead less
Defining how serotonin regulates gut motility. This project aims to deepen knowledge of gastrointestinal physiology, and reveal the mechanisms by which the major gastrointestinal signalling molecule, serotonin, regulates gut peristalsis. Almost all of the serotonin in our body is made in the gastrointestinal tract where it controls many functions, including how our gut wall contracts during peristalsis. Proper control of gut peristalsis and the transit of material through our bowel is important ....Defining how serotonin regulates gut motility. This project aims to deepen knowledge of gastrointestinal physiology, and reveal the mechanisms by which the major gastrointestinal signalling molecule, serotonin, regulates gut peristalsis. Almost all of the serotonin in our body is made in the gastrointestinal tract where it controls many functions, including how our gut wall contracts during peristalsis. Proper control of gut peristalsis and the transit of material through our bowel is important for our health. This project expects to define how serotonin controls peristalsis, where in the bowel this serotonin comes from, how serotonin communicates with the nervous system in our gastrointestinal tract, and how the cells that synthesise gut serotonin respond to contraction to trigger the secretion of serotonin.Read moreRead less
Alcoholic Chronic Pancreatitis: Induction, Progression And Reversal
Funder
National Health and Medical Research Council
Funding Amount
$632,211.00
Summary
Pancreatitis (inflammation of the pancreas) is a serious complication of alcohol abuse. Patients suffer from severe and often intractable abdominal pain, maldigestion and diabetes, We have recently shown that gut toxins (endotoxins) may act as a trigger factor for pancreatitis in alcoholics. The proposed project aims to characterise the effects of gut toxins on the pancreas during alcohol abuse so as to identify pathways that may be therapeutically targeted to prevent or retard the disease.
Transcutaneous Electrical Stimulation To Relieve Chronic Constipation In Children
Funder
National Health and Medical Research Council
Funding Amount
$346,995.00
Summary
We have over 300 children with chronic treatment-resistant constipation at Royal Children's Hospital Melbourne. We have a new physiotherapy technique that may overcome constipation and stop soiling in many of these children. In 2003-4, we ran a pilot study to test a technique used by physiotherapists to treat urinary incontinence. We have called the method TESIC (transcutaneous electrical stimulation using interferential current). TESIC uses suction electrodes placed on the belly and back at the ....We have over 300 children with chronic treatment-resistant constipation at Royal Children's Hospital Melbourne. We have a new physiotherapy technique that may overcome constipation and stop soiling in many of these children. In 2003-4, we ran a pilot study to test a technique used by physiotherapists to treat urinary incontinence. We have called the method TESIC (transcutaneous electrical stimulation using interferential current). TESIC uses suction electrodes placed on the belly and back at the level of the belly button. The electrical stimulation is applied using a current (interferential current) that stimulates deep into the abdomen. We tested 8 children and had very encouraging results with improved constipatio in 5-8 and all with soiling stopped. Parents and children are keen to use this technique but first we need to establish that the results are reproducible in a larger group of 70 children. We also need to know if the effect was just a placebo response (due to time spent with the physiotherapists), and how long the effect lasts. We will also measure changes in soiling. Faecal soiling is smelly and antisocial. Relief of soiling has a big impact on a child's ability to fit in at school and to attend normal schooling. We will measure outcomes using daily diaries kept by children, questionnaires, how quickly food moves through the bowel and pressures within the bowel. We have a multidiciplinary team of experienced clinicians and scientists with expertise in these techniques and in constipation and incontinence in children (paediatric surgeon, gastroenterologist, manometry nurse, incontinence paediatrician and physiotherapist, expert in electrical stimulation and gut nervous system scientist). This technique could revolutionise treatment of chronic constipation. Most physiotherapists have TESIC machines, allowing delivery Australia wide. It is non-invasive and should also be able to be used by adults, including the elderly in nursing homes.Read moreRead less
Proteomics And Confocal Endomicroscopy In The Evaluation Of Inflammatory Bowel Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$436,096.00
Summary
Inflammatory bowel diseases (IBD) result in devastating consequences and affect more young Australians than epilepsy or road traffic accidents. Damaged bowel results in loss of the normal gut barrier and flora can enter the tissue and even the blood. This concept of the "leaky gut" has been previously difficult to demonstrate. This can now be seen and measured using two new technologies called proteomics and confocal endomicroscopy. These tests offer new avenues of research for the 61,000 Austra ....Inflammatory bowel diseases (IBD) result in devastating consequences and affect more young Australians than epilepsy or road traffic accidents. Damaged bowel results in loss of the normal gut barrier and flora can enter the tissue and even the blood. This concept of the "leaky gut" has been previously difficult to demonstrate. This can now be seen and measured using two new technologies called proteomics and confocal endomicroscopy. These tests offer new avenues of research for the 61,000 Australian sufferers of IBD.Read moreRead less