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
Cell Surface Mucins In Gastrointestinal Mucosal Innate Immunity
Funder
National Health and Medical Research Council
Funding Amount
$475,500.00
Summary
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. We have recently identified three of the seven genes currently known to produce this type of molecule. We propose that mucins have a very important role in maintaining the barrier between potentially infectious microorganisms often present in epithelial tracts and the internal organs. We also believe 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. We have recently identified three of the seven genes currently known to produce this type of molecule. We propose that mucins have a very important role in maintaining the barrier between potentially infectious microorganisms often present in epithelial tracts and the internal organs. We also believe that these molecules trigger epithelial cell defensive responses to the presence of microorganisms. The proposed research aims to prove these propositions and to elucidate the molecular mechanisms underlying function of cell surface mucins. Understanding the function of cell surface 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
Structure And Functional Characterisation Of AB5 Toxins
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
The proposed research program, using a combination of structure and biochemical analyses, will provide insight into two novel AB5 toxins that represent a medically important family of proteins. This study will not only improve our fundamental understanding of AB5 toxins action but could lead to rational design of antimicrobials.
Roles Of The Peptide Hormone, Ghrelin, In The Spinal Cord
Funder
National Health and Medical Research Council
Funding Amount
$414,326.00
Summary
This study investigates the control of internal organs of the body, the heart, blood vessels, intestine and bladder. We have made the new and surprising discovery that ghrelin, previously known to be a hormone, is probably also a neurotransmitter in the spinal cord. This raises the possibility that drugs that act on ghrelin receptors in the spinal cord could be used to treat high blood pressure or other problems of internal organs.
Glucose is a critical fuel for living organisms and its presence in the gut triggers nerves that slow stomach emptying. However, little is known of how glucose is actually detected in the gut. We have established that sweet taste molecules of the tongue are also present in the gut, where they may detect glucose. This research will measure the expression and function of these molecules in the gut of humans and mice, and reveal key information on their potential as targets in health and disease.
The Role Of The ABCA12 Transporter In Epidermal Lipid Homeostasis And Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$516,401.00
Summary
We have shown that a protein called Abca12 can control the transport of lipids in our bodies. If the function of this gene is attenuated both human and mice develop severe skin disease. Our preliminary results indicate the Abca12 protein regulates cholesterol transport in particular, and this grant will investigate how this might affect normal skin function and contribute to the heart disease atherosclerosis, one of the most common causes of death in the western world.
Gastrointestinal Function And Appetite In Obesity - Acute And Longer-term Effects Of Changes In Energy Intake
Funder
National Health and Medical Research Council
Funding Amount
$744,645.00
Summary
The prevalence of obesity is assuming epidemic proportions. While weight loss diets help people to lose weight, body weight stabilises over time despite continued dieting. Our research proposal represents a novel initiative with the aim to understand the adaptations in gastrointestinal mechanisms in response to acute and longer-term dietary restriction that compromise weight loss. Ultimately our research will help to develop weight loss strategies that are successful in the long-term.
The role of the immune system in pain is emerging from recent discoveries, and may hold the key to novel pain treatments. Most people experience brief gut infections from food or contagion without long-term consequences. Many others suffer symptoms for years afterwards - probably the best example of immune-based pain. Our project investigates how immune cells communicate with sensory nerves, and how these communications change from both angles after gut infection or inflammation.