Functional Relationships Of Gastrin And Its Regulators In The Developing And Diseased Gastrointestinal Tracts
Funder
National Health and Medical Research Council
Funding Amount
$607,832.00
Summary
Gastrin is a hormone from the stomach which aids digestion by stimulating acid secretion. However too much acid can cause ulcers of the gastrointestinal tract. Gastrin also stimulates growth of the lining of the stomach and intestines. This growth promoting effect is important for the development of the gastrointestinal tract before birth and may also be involved in a number of cancers especially colon cancer. Several different forms of gastrin are made by endocrine cells of the stomach and by c ....Gastrin is a hormone from the stomach which aids digestion by stimulating acid secretion. However too much acid can cause ulcers of the gastrointestinal tract. Gastrin also stimulates growth of the lining of the stomach and intestines. This growth promoting effect is important for the development of the gastrointestinal tract before birth and may also be involved in a number of cancers especially colon cancer. Several different forms of gastrin are made by endocrine cells of the stomach and by cancers of the colon. It seems that the different types of gastrins have different effects and act through distinct receptors. The production and effects of gastrin are mediated in part by the local factor histamine and modified by the hormone somatostatin. The amount, type and activity of gastrin, and the interactions with histamine and somatostatin, will be measured in foetal and newborn animals, and people with or at risk of developing colon cancer.Read moreRead less
The Impact Of Virulence Gene Polymorphisms On Helicobacter Pylori Pathogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$448,434.00
Summary
The bacterium Helicobacter pylori causes various types of disease of the stomach and intestine. It is still not clear, however, why some infected individuals develop very severe forms of disease (ulcers or cancer) whilst others develop only inflammation. This project will investigate H. pylori interactions with cells that line the stomach wall and how these interactions may contribute to the development of more severe disease.
The Role Of The Gastric H/K ATPase In Parietal Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$166,885.00
Summary
The cells of the body contain many specialised membrane structures. At present it is not clear how the synthesis of these stuctures is directed. To study this problem we are examining the acid secretory parietal cells of the stomach. These cells have a very elaborate membrane system that contains a major proton pump protein. By manipulating the levels and form of the proton pump we will gain novel insights into the mechanism of membrane structure and function.
Secretion is an essential step in memory and learning, control of metabolism and reproduction and the functioning of most organs. Secretory dysfunction also underlies many diseases including type 2 diabetes. We plan experiments to test for a new model of control of insulin secretion.
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