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.
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.
GABA(B) Receptor Modulation Of Gastrointestinal Function In Health And Disease By Alpha-Conotoxins
Funder
National Health and Medical Research Council
Funding Amount
$689,050.00
Summary
Chronic visceral pain is a common and debilitating condition arising from numerous diseases that affect our internal organs. There is a desperate need for more information about the mechanisms responsible for signalling chronic visceral pain to provide therapies and potentially find a cure for it. Our research focuses on ?-conotoxins (small peptides from marine cone snail venom) as novel potential therapeutic agents for the treatment of chronic visceral pain.
Determining The Mechanisms Underlying Chronic Visceral Pain And Providing Novel Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
Gastroenteritis activates special types of nerve endings in the gut to cause acute pain. In chronic gut pain, although the damaged tissue has healed, the nerve endings remain active and don’t reset back to normal. This project will identify why this occurs, determining pain mechanisms associated with Irritable Bowel Syndrome, a leading form of chronic pain. It will identify which ion channels and receptors can be targeted allowing the development of novel and effective therapies for pain relief.
The role of the immune system in pain is emerging from recent discoveries, and may hold the key to novel pain treatments. Most people experience brief gut infections from food or contagion without long-term consequences. Many others suffer symptoms for years afterwards - probably the best example of immune-based pain. Our project investigates how immune cells communicate with sensory nerves, and how these communications change from both angles after gut infection or inflammation.
Transient Receptor Potential Channels (TRPs) As Transducers And Targets In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$669,130.00
Summary
Transient receptor potential, or TRP channels, are involved in generating many of the sensations we perceive, such as heat, cold, touch and pain. Some TRP channels are specialized to signal pain from visceral organs, which we must investigate if we are to find treatments for visceral pain, which are currently lacking.
Development Of Diagnostic Tools To Characterise Predictors Of Therapeutic Outcome In Severe Constipation
Funder
National Health and Medical Research Council
Funding Amount
$433,999.00
Summary
This project will use fibre-optic technology to create detailed high resolution maps of colonic motor patterns in both health and in patients with severe constipation. The data will be used in combination with actual patient symptoms to help identify specific markers of disease that can differentiate sub-types of constipation and ultimately guide and improve treatment in constipated patients
Ion Channels Underlying Inflammatory And Post-inflammatory Visceral Mechanical Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$453,439.00
Summary
Inflammation causes tissue damage that triggers ion channels within sensory nerve fibres to produce greater signals in response to mechanical events, causing acute pain. In chronic pain, although the inflamed tissue has healed, sensory nerve fibres fail to "reset" back to normal. Often chronic pain is more severe than acute pain. This project will identify which ion channels are responsible for signalling acute and chronic visceral pain, explaining why sensory nerve fibres fail to reset.
Effects Of The Fatty Acid, Lauric Acid, On Energy Intake And Gut Motor And Hormonal Function In Health And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$744,645.00
Summary
Obesity is largely due to energy intake exceeding energy expenditure, thus, strategies that reduce energy intake will result in weight loss. We discovered recently that the fatty acid, lauric acid, markedly reduces energy intake. Our studies will determine the effects of lauric acid on energy intake and body weight reduction in obese subjects. The research is a new initiative and explores the potential of lauric acid as a novel, nutrient-based and side-effect free approach to obesity management.