How Intestinal Motility Activates Sensory Pathways
Funder
National Health and Medical Research Council
Funding Amount
$555,875.00
Summary
Pain and discomfort from the gut are common and unpleasant. We understand how gut sensory nerve cells work, at the cellular, molecular and genetic level. However, movement of the gut wall and contents are the major cause of activation of sensory neurons. We know little about which particular patterns of movement cause pain. This is crucial information for accurately diagnosing human gut disorders, for monitoring effectiveness of treatments and for identifying potential new drug targets.
Mechanical Factors In Normal Human Colonic Motility
Funder
National Health and Medical Research Council
Funding Amount
$650,023.00
Summary
Abnormal human colonic contractions cause significant medical, societal and financial burdens. Diagnosis and treatment of motility disorders requires an understanding of normal colonic contractility against which to measure dysfunction. Through state-of-the-art recording and analytical techniques, developed by the applicants, this project will provide the first clear description of normal human colonic motor patterns and how they are generated.
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.
The migration of cancer cells (metastasis) is responsible for most cancer deaths. Central to this is dynamic organisation of the actin cytoskeleton _ an internal structure that provides cell shape and enables movement. We have identified a family of small molecules (called miR-200) that regulates this actin cytoskeleton through specifically downregulating various genes. We are investigating the nature of these genes and their role in cell motility _ an underlying pre-requisite of metastasis.