Gastrokine 2 Promotes Gastric Homeostasis And Inhibits Bacterial Pathology
Funder
National Health and Medical Research Council
Funding Amount
$621,335.00
Summary
Gastrokine 2 is a small regulatory protein secreted by the stomach lining. Its function is unknown but data from our lab suggests that it may be important in maintaining stomach integrity. This project will investigate how gastrokine 2 maintains stomach function, how this can be compromised when bacterial infection is ongoing, and how we might be able to turn up gastrokine 2 expression to prevent inflammation and precancerous changes in the stomach lining.
Factors Regulating Initiation, Progression And Submucosal Invasion In Gastric Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$450,750.00
Summary
Gastric cancer is the second most common cause of death in humans. It is strongly associated with Helicobacter pylori, a common and easily transmitted bacterium which infects about half the world's population. Exactly how Helicobacter pylori (HP) causes cancer, and why it does so in only a small percentage of those infected is unknown. It is clear however that Helicobacter species that produce a strong inflammatory response in the host and possess a full complement of pathogenic (disease-associa ....Gastric cancer is the second most common cause of death in humans. It is strongly associated with Helicobacter pylori, a common and easily transmitted bacterium which infects about half the world's population. Exactly how Helicobacter pylori (HP) causes cancer, and why it does so in only a small percentage of those infected is unknown. It is clear however that Helicobacter species that produce a strong inflammatory response in the host and possess a full complement of pathogenic (disease-associated) genes are more strongly associated with cancer development after long-term infection than others. We have recently developed a genetically modified mouse which has a minor defect in a regulatory pathway which controls some aspects of gut inflammation. Surprisingly 100% of these mice rapidly develop gastric cancer which has many similarities with the human disease, including inflammation, loss of structure of the stomach lining and penetration of cancerous cells into the muscle layers below. The objectives of this project are to work out whether HP induces similar changes in normal stomach cells as occurs in our defined mouse model of gastric cancer. Specifically we will determine if HP disturbs the way a particular mediator of inflammation works, and if so the way this impacts on certain stomach genes which detect cancerous cells and prevent tumor growth.Read moreRead less
Mechanisms Of Action Of The Trefoil Peptides In Promoting Healing In Models Of Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$365,270.00
Summary
Preliminary experiments from our laboratory have shown that members of a family of small proteins called trefoil peptides, found naturally in the stomach, intestine and colon, are able to shorten the healing time of ulcers and reduce inflammation, in an animal model of inflammatory bowel disease. Crohn's disease and ulcerative colitis together make up the human inflammatory bowel diseases, or IBD for short. They afflict many members of the community, are debilitating, expensive to treat, and cur ....Preliminary experiments from our laboratory have shown that members of a family of small proteins called trefoil peptides, found naturally in the stomach, intestine and colon, are able to shorten the healing time of ulcers and reduce inflammation, in an animal model of inflammatory bowel disease. Crohn's disease and ulcerative colitis together make up the human inflammatory bowel diseases, or IBD for short. They afflict many members of the community, are debilitating, expensive to treat, and current treatments like corticosteroids and suppressors of the immune system have unpleasant and health-threatening side effects. There are therefore good reasons for the development of new forms of therapy which will be better tolerated and which are specific in their actions. We believe that the trefoil peptides may be good candidates on which new treatments for inflammatory disease might be based. The studies outlined in this proposal will test the best route of administration, and how often to give trefoil peptides in order to relieve the symptoms of experimental IBD. In addition the effectiveness of the trefoils will be compared to other agents currently used in IBD treatment, or which are known to relieve inflammation or speed the healing of the ulcerated colon. We will also carry out experiments designed to work out the mechanisms by which the trefoils' healing effects are mediated, and finally we will characterise a new member of the trefoil peptide family which we have recently discovered.Read moreRead less
Novel Candidate Genes, Lung Function And Allergic Airways Disease
Funder
National Health and Medical Research Council
Funding Amount
$581,892.00
Summary
We propose to study airway remodelling (structural changes to the airway) and in asthma using human samples and rodent models of asthma. We are particularly interested in investigating the role of trefoil peptide 2 and relaxin, two genes identified as determining lung function. To do this we need to understand the mechanisms of airway remodelling and its impact on disease severity in the patient. A strength of this study is availability of samples from a large study of human asthma.