Understanding The Relationship Of Incretin Hormones, Gastric Emptying And Reactive Hypoglycaemia
Funder
National Health and Medical Research Council
Funding Amount
$132,743.00
Summary
Low blood glucose levels following a meal occur frequently in otherwise healthy people and those who have had surgery for weight loss. It affects quality of life adversely and current management is unsatisfactory. The proposed studies will use sophisticated techniques to evaluate the roles of the rate of stomach emptying and the so-called 'incretin' hormones which stimulate the release of insulin after a meal. The outcomes will have major implications for more rational management.
Establishment Of A Biomarker To Test Molecular Risk Of Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$834,448.00
Summary
Less than 20% of patients live 5 years after a diagnosis of gastric cancer (GC). This is due to the advanced stage at the time of diagnosis. We have no markers to monitor therapy of cancer. This proposal aims to use next generation sequencing to find specific genetic changes in a persons tumour that can be used to monitor therapy. We aim to use the same technology to group patients into high-risk or low risk for development of GC. This will allow specific screening only for those at high-risk.
Structural Basis For Helicobacter Pylori Adhesion To Host Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$665,328.00
Summary
The aim of this grant is to understand how the bacteria that cause gastric cancer and ulcers interact with the cells that line the stomach. This information will be used to develop new treatments to combat disease.
Acid Resistance Mechanisms Of Helicobacter Pylori And Their Impact On Gastric Colonisation
Funder
National Health and Medical Research Council
Funding Amount
$287,036.00
Summary
The gastric bacterium, Helicobacter pylori, infects more than half the population of the globe. H. pylori may cause either no symptomatic disease, induce peptic ulcers or be responsible for one of the major killing cancers, gastric cancer. Millions die or suffer from this infection each year. Yet we are remarkably ignorant of why the infection causes these different patterns of disease. This project aims to provide evidence to show that the very mechanism the bacterium has acquired to help it re ....The gastric bacterium, Helicobacter pylori, infects more than half the population of the globe. H. pylori may cause either no symptomatic disease, induce peptic ulcers or be responsible for one of the major killing cancers, gastric cancer. Millions die or suffer from this infection each year. Yet we are remarkably ignorant of why the infection causes these different patterns of disease. This project aims to provide evidence to show that the very mechanism the bacterium has acquired to help it resist stomach acid and so live in the stomach, is responsible for these differences. I.e. The organism lives in different parts of the stomach due to differences in local acid at that site. If the acid in a particular part of the stomach is too high, the acid resistance mechanism cannot cope. If the acid is too low, the organism also cannot grow well. Because the bacterium has evolved to only thrive in a relatively narrow range of acid, it will behave very differently in these different parts of the stomach. This results in different diseases. Various populations in different countries of the world have different levels of acid production and this also explains why in some countries duodenal ulcers predominate and in others gastric ulcer- gastric cancer is the norm. Showing why H. pylori lives where it lives will provide fundamental information relevant to understanding some of the world s major diseases and will also provides insights relevant to the design of new therapeutic approaches.Read moreRead less
Improving Efficacy Of Vaccination Against The Gut Pathogen Helicobacter Pylori
Funder
National Health and Medical Research Council
Funding Amount
$504,000.00
Summary
Helicobacter pylori are bacteria which live in the stomachs of half the World's population, where they are the main cause of two types of stomach cancers, as well as stomach and duodenal ulcers. The development of a vaccine against this organism would have a major impact on these diseases. Unfortunately, while there has been some success in animal models, the results from clinical trials have so far been disappointing. A key issue with vaccines against H. pylori is their poor efficacy, i.e. alth ....Helicobacter pylori are bacteria which live in the stomachs of half the World's population, where they are the main cause of two types of stomach cancers, as well as stomach and duodenal ulcers. The development of a vaccine against this organism would have a major impact on these diseases. Unfortunately, while there has been some success in animal models, the results from clinical trials have so far been disappointing. A key issue with vaccines against H. pylori is their poor efficacy, i.e. although they produce a significant reduction in bacteria numbers in animal models, they do not clear all of the bacteria. The remaining bacteria are sufficient to continue to cause disease. It is currently not understood how these vaccines work in mice, which makes it very difficult to improve their design. An additional problem common to all human vaccines, is the lack of a suitable adjuvant. An adjuvant is a non-specific vaccine component which is required to activate the immune system. Thus, for an effective vaccine it is essential to identify suitable adjuvants which will work against H. pylori and can be used in people. The chief investigator on this project has been working in the H. pylori vaccine field, in both academia and industry, for 8 years. He very recently identified an immunisation regime which greatly increases the effectiveness of vaccination against H. pylori in an animal model. The main aim of this project is to further develop this novel discovery to identify key immune factors that are critical to making an improved vaccine. In addition, the two associate investigators are experts in the area of adjuvants for human vaccines, and will help to test new vaccine systems in the H. pylori model. If successful, this project will generate highly significant data that will strongly contribute towards the design of an improved vaccine strategy against H. pylori in people.Read moreRead less
The Role Of Capsulin, A New BasicHelix-Loop-Helix Factor, In Differentiation And Repair Of The Gastric Mucosa.
Funder
National Health and Medical Research Council
Funding Amount
$131,812.00
Summary
We aim to understand the role that a new factor plays in the processes whereby the lining of the stomach is continually renewed, and also repaired after injury due to inflammation and ulceration. Once we understand the role of this factor and how it works, we may be able to use this factor as a therapeutic to prevent the initial formation of inflammation and ulceration in the stomach that can lead to more serious diseases, such as cancer.
Helicobacter Pylori VacA Toxin: Modulation Of Human Mitochondrial Function By A Bacterial Pathogen
Funder
National Health and Medical Research Council
Funding Amount
$508,003.00
Summary
This work will greatly further our understanding of how a bacterium, Helicobacter pylori, causes stomach ulcers and cancer. We will use cutting edge model systems to study the VacA toxin that is secreted from the bacteria and is targeted to human cells. We will examine where the toxin goes and how it affects our cells. It is expected that the improved understanding that will arise from this work will assist researchers to better devise drugs against this prevalent pathogen.
Mechanics Of Normal And Disordered Gastric Emptying Studied Using Simultaneous Ultrasound And High Resolution Manometry
Funder
National Health and Medical Research Council
Funding Amount
$145,626.00
Summary
Optimal digestion and absorption relies on the stomach breaking down food and delivering it to the small intestine at an optimal rate. Abnormalities in the processes controlling the stomach's processing of food may lead to malnutrition, gastrointestinal symptoms or unpredictable drug absorption, and are commonly seen in patients with diabetes mellitus, gastrointestinal reflux disease and nonulcer dyspepsia, or following stomach surgery. Currently our understanding of the way the stomach empties ....Optimal digestion and absorption relies on the stomach breaking down food and delivering it to the small intestine at an optimal rate. Abnormalities in the processes controlling the stomach's processing of food may lead to malnutrition, gastrointestinal symptoms or unpredictable drug absorption, and are commonly seen in patients with diabetes mellitus, gastrointestinal reflux disease and nonulcer dyspepsia, or following stomach surgery. Currently our understanding of the way the stomach empties food is incomplete, and there is little information as to the mechanisms by which diseases cause abnormal stomach emptying. Recent developments in recording methods mean that we can now simultaneously measure stomach contractions, the pressures these generate and flow from the stomach. This information is synchronised and displayed for analysis using computer techniques. In this project these novel methods will be used initially to examine the normal processes by which meals with a variety of compositions and consistencies empty from the stomach. This will provide information as to which aspects of the way the stomach functions are important for breaking down food into particles, and which aspects control the flow of food from the stomach into the intestine. The mechanisms by which the rate of emptying of the stomach is controlled by feedback signals caused by the presence of foodstuffs in the small intestine will be investigated by examining the effects of infusing nutrients into the intestine on the motions of the stomach wall, pressures within the stomach and the passage of stomach contents into the small intestine. The mechanism of action of drugs and diseases which slow stomach emptying will then be examined by measuring the movements, pressures and emptying of the stomach in subjects receiving the drug, or in patients with dibetes, and comparing this information with the processes observed during normal stomach emptying.Read moreRead less