Life-threatening Ulcer Complications In The Elderly: Role Of Visceral Sensory Function And Molecular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$445,011.00
Summary
A large proportion of patients with chronic disease such as peptic ulcer disease present with life-threatening complications such as severe peptic ulcer bleedings without any relevant symptoms prior to the manifestation of the complication. This lack of symptoms can be considered the main reason that the disease is not earlier diagnosed or before severe complications such as life-threatening bleeding ulcers occur.
Vaccinating Against Helicobacter Pylori-induced Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,088,714.00
Summary
Stomach cancer is the 3rd leading cause of cancer-related deaths. Most stomach cancers result from inflammation due to Helicobacter pylori infection. Most infections are treatable with antibiotics but this does not protect against cancers that develop before infection is diagnosed. Normal vaccine approaches aimed at this infection have been unsuccessful. We have identified a new approach for protecting against stomach cancer by preventing inflammation; this project aims to develop this vaccine.
Identification Of Novel Colonisation Factors In Helicobacter Pylori
Funder
National Health and Medical Research Council
Funding Amount
$336,142.00
Summary
The discovery by Drs Marshall and Warren of the bacterium Helicobacter pylori, and its role in stomach disease, has proven to be one of the major break-throughs of the late 20th century. Indeed, several common ailments of the upper digestive tract that were once thought to be untreatable, or which could only be treated by radical surgery, are now managed through the use of antibiotics and acid-blocking substances. The efficacy of these treatments has, however, been affected by the increasing rat ....The discovery by Drs Marshall and Warren of the bacterium Helicobacter pylori, and its role in stomach disease, has proven to be one of the major break-throughs of the late 20th century. Indeed, several common ailments of the upper digestive tract that were once thought to be untreatable, or which could only be treated by radical surgery, are now managed through the use of antibiotics and acid-blocking substances. The efficacy of these treatments has, however, been affected by the increasing rates of H. pylori resistance to these antibiotics in the general community. Furthermore, the limited choice of antibiotics available for use in anti-H. pylori treatment regimens, and the side-effects associated with several of these compounds, suggest that there is a need to develop new therapies against this bacterial infection. This, however, will necessitate a greater understanding of the mechanisms by which H. pylori is able to colonise and survive in the mucus layer covering the stomach. To address this point, we have used a gene profiling technique to compare gene expression in H. pylori bacteria displaying high and low levels of colonisation in a mouse model. For this, mouse-colonising H. pylori bacteria were attenuated through extensive passaging on culture media in the laboratory. Five genes were identified as being poorly expressed in the attenuated bacteria. These genes are proposed to encode putative H. pylori colonisation factors. The aim of the project is to characterise these factors, and to determine the roles of two of these, which are involved in the production of vitamin B6, in the colonisation of the stomach. This work will contribute to a greater understanding of the factors involved in H. pylori colonisation of the stomach. Amongst the possible public health benefits of this work is the identification of molecular targets for the development of new therapies for the prevention and treatment of H. pylori infection.Read moreRead less
Improving Ubiquitous Interventions To Optimise Outcomes From Critical Illness
Funder
National Health and Medical Research Council
Funding Amount
$333,710.00
Summary
A/Prof Deane is a specialist intensive care physician who combines clinical work at The Royal Melbourne Hospital with a large research program. The research supported by this Fellowship will translate to fundamental changes in the administration of ubiquitous interventions and will optimise management of conditions that occur frequently in the critically ill and represent a major source of mortality, morbidity and healthcare utilisation/costs.
Protease-activated Receptor-1 (PAR-1) And Regulation Of Helicobacter Pylori Induced Mucosal Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$478,090.00
Summary
Helicobacter pylori infections cause chronic gastritis which in some people results in stomach cancer or ulcers. We have identified a novel host factor, PAR-1, important for preventing this inflammation. We will use mice to identify how this molecule protects against gastritis and samples from patients to examine its importance in human disease. This will help explain why these diseases develop in some people but not others and perhaps allow identification of those at risk of developing disease.
Potassium Channel Regulation Of Bacterial-driven Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$576,000.00
Summary
Helicobacter pylori infections cause a chronic inflammation which in some people results in stomach cancer or ulcers. We have used a mouse with natural resistance to H. pylori gastritis to identify a completely novel regulator of the pathology induced by this infection. In this project, we will examine the mechanism by which this regulator protects against disease in mice, and examine its significance in the susceptibility of people to gastric cancer.