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.
Characterization Of Novel, Colitis Associated Pathobionts To Identify Therapeutic Targets In The Host Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$684,609.00
Summary
Applying cutting edge methods to grow bacteria from the human gut, we have identified three species, two previously unknown, that are found in many inflammatory diseases including Inflammatory bowel disease, colorectal cancer and in cancer immunotherapy patients who experience colitis. By characterizing these bacteria and the immune response in human cells we are seeking to discover novel targetted methods to prevent colitis and gastrointestinal inflammation.
Stimulant laxatives are widely used and usually very effective in the short term, but how they work is very poorly understood. Our recent work has shown that they selectively excite sensory pathways from the colon which then trigger defaecation. This points to an undiscovered mechanism that potently affects colonic sensation and motility. This is likely to be a target for new treatments for other colonic disorders such as Irritable bowel syndrome and faecal incontinence.
Irritable Bowel Syndrome (IBS) is one of the leading causes of chronic pain both world-wide and in Australia for which there is a lack of treatments. Chronic pain arises from nerve fibres in the colon wall, which fail to 'reset' back to normal following inflammation. Targeting these nerve endings with drugs is a key advance in IBS treatment. This project will identify selective oxytocin analogues that act in the colon to lower pain in sensory nerves thus providing efficacious pain relief in IBS.
Anti-sporulation Strategies For Clostridium Difficile Infections
Funder
National Health and Medical Research Council
Funding Amount
$651,559.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with highly virulent isolates emerging overseas in 2002 and in Australia in 2010. These strains have spread through our hospitals and are also found in the community. This project will increase our understanding of how these strains spread and will provide knowledge that is critical for developing improved strategies for preventing these infections.
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.
Norovirus Infection At The Stress Granule-PKR-p-elF2α Axis
Funder
National Health and Medical Research Council
Funding Amount
$505,967.00
Summary
This project application will aim to investigate and understand how viruses that cause vomiting and diarrhoea are able to infect, proliferate and spread within the human body. It aims to address how viruses are able to avoid and replicate in the presence of an effective immune response. We have evidence showing that Noroviruses are able to exploit certain antiviral proteins to paradoxically aid in virus replication and survival.
A Novel Therapeutic Target For Preventing Helicobacter Pylori-associated Diseases
Funder
National Health and Medical Research Council
Funding Amount
$750,336.00
Summary
Gastric cancer mainly results from chronic inflammation (gastritis) caused by the stomach-dwelling bacterium, Helicobacter pylori. We have identified a potassium channel which our data suggest could be a new therapeutic target for protecting against gastric cancer caused by H. pylori infection. This project will test the role of this channel in H. pylori gastritis and see whether drugs that target this channel can protect mice against H. pylori-associated disease.
Many infants and children suffer from bowel motility disorders, for example, chronic constipation affects up to 1 in 10 children. However, the cause of many of these paediatric motility disorders remains unknown. In this project, we will examine the development of wiring of the nervous system that controls bowel motility. This is the first study to investigate the development of cell-cell communication during early stages of nervous system development.
Re-EValuating The Inhibition Of Stress Erosions (REVISE): Gastrointestinal Bleeding Prophylaxis In ICU
Funder
National Health and Medical Research Council
Funding Amount
$2,955,164.00
Summary
Around 50,000 patients in Australian Intensive Care Units receive a drug called pantoprazole each year with the aim of preventing bleeding from the gut. Recent research suggests this practice is ineffective and may harm patients by increasing their risk of serious infections. We will perform a definitive study to determine whether the widespread use of pantoprazole is beneficial or harmful.