Mechanisms Of Action Of Neurochemicals And Modulators In Human Intestine: Changes In Disease
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Inflammatory bowel disease (IBD) and idiopathic chronic constipation (ICC) are two serious gastrointestinal disorders, for which no effective medical treatment is known. We will investigate the hypothesis that abnormalities in the nerve chemicals found in the gut contribute to the aetiology of these diseases. Our studies will examine the sites of action (receptors) for these chemicals (neurotensin and acetylcholine) in the small and large intestine. The mechanisms governing motility changes in r ....Inflammatory bowel disease (IBD) and idiopathic chronic constipation (ICC) are two serious gastrointestinal disorders, for which no effective medical treatment is known. We will investigate the hypothesis that abnormalities in the nerve chemicals found in the gut contribute to the aetiology of these diseases. Our studies will examine the sites of action (receptors) for these chemicals (neurotensin and acetylcholine) in the small and large intestine. The mechanisms governing motility changes in response to these chemicals have been well studied in animal intestine, but there is little detailed information from the human intestine. This study will provide insight into the mechanisms operating in the normal bowel, providing a base for comparing bowel obtained from patients with IBD or ICC. We will also study bowel removed at surgery for acute diverticular disease (DD), representing another type of inflammation. Studies on isolated segments of colon from ICC patients will determine whether the contractility of the muscle is abnormal in general or only with respect to the chemicals under investigation. Other studies will investigate the inflammatory processes occurring in the bowel and whether this differs in IBD. Our work will facilitate understanding of the function of the bowel in health and in gastrointestinal disorders and may lead to new medical treatments for IBD and ICC.Read moreRead less
Rhythmicity And Synchronicity In Uterine Smooth Muscle
Funder
National Health and Medical Research Council
Funding Amount
$291,823.00
Summary
Natural birth occurs through rhythmic contractions of the smooth muscle of the uterus. There is surprisingly little understanding of the mechanism of the pacemaker clock that both initiates and times each contraction in a coordinated manner to expel the fetus. This project is to challenge this knowledge gap using our findings on cellular rhythms that herald Ca2+ stores as a major pacemaker mechanism. First, we will use electrophysiology and calcium imaging techniques to test the hypothesis that ....Natural birth occurs through rhythmic contractions of the smooth muscle of the uterus. There is surprisingly little understanding of the mechanism of the pacemaker clock that both initiates and times each contraction in a coordinated manner to expel the fetus. This project is to challenge this knowledge gap using our findings on cellular rhythms that herald Ca2+ stores as a major pacemaker mechanism. First, we will use electrophysiology and calcium imaging techniques to test the hypothesis that rhythmicity and synchronicity of uterine contractions are underpinned by store pacemaking. Second, we will probe the role of current spread between cells via gap junctions as a mechanism of recruitment and will examine whether accessory cells termed interstitial cells subserve a role in pacemaking. These cells are present within the uterine wall but their function is unknown. We will probe their ion channel properties in relation to pacemaking using patch clamp techniques. Third, we will examine the role of labour hormones, such as oxytocin, in augmenting uterine contractions via interaction with the Ca2+ store mechanism and cell recruitment. These studies will provide new and fundamental insights into uterine pacemaking, an outcome that should be of great significance to understanding and better controlling birth-associated complications such as preterm delivery and failure to progress.Read moreRead less
A vitamin-sized capsule, containing gas sensors, is to be fully developed for assessing the state of health and diagnosing the diseases relevant to gastrointestinal tract. The capsule travels along the tract, transmitting information about the gas species generated by the microorganisms of the gut, which is closely associated with the health of the human under surveillance. The information will be invaluable for diagnostics and adjusting the diet to mitigate and cure the diseases of the guts.
Neuroimmune Interactions In Functional And Organic Gastrointestinal Diseases
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) are chronic, incurable diseases of the lower gastrointestinal tract with unknown causes and poor treatment options. Both the immune and nervous systems are altered in GI disease, but have traditionally been studied in isolation. My research investigates how the neuro-immune axis is altered in these diseases, using animal models and human tissue samples to identify novel treatment options for these debilitating diseases.
Vagal Nerve Stimulation As A Novel Therapy In Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$88,502.00
Summary
Inflammatory bowel disease (IBD) is common exerting a large personal and societal burden to the Australian population. Current medications used to treat IBD are expensive, have many side effects and at times require hospitalisation for their administration. We aim to develop the non invasive and inexpensive technique of vagal nerve stimulation as a novel treatment strategy for IBD.
The Effects Of Intestinal Inflammation On The Currents And Channels Of Identified Enteric Neurons
Funder
National Health and Medical Research Council
Funding Amount
$476,264.00
Summary
Intestinal inflammation, in gastroenteritis, Crohn's disease, ileitis or colitis, has effects on the motility (movement) of the gastrointestinal and on secretion within it. The symptoms that are recognised are poor digestion, crampy pains and diarrhoea. The symptoms often continue after the inflammation has subsided. The major disease entity that can develop after inflammation is the irritable bowel syndrome (IBS). IBS is associated with persistent disorders of bowel motility. The symptoms are t ....Intestinal inflammation, in gastroenteritis, Crohn's disease, ileitis or colitis, has effects on the motility (movement) of the gastrointestinal and on secretion within it. The symptoms that are recognised are poor digestion, crampy pains and diarrhoea. The symptoms often continue after the inflammation has subsided. The major disease entity that can develop after inflammation is the irritable bowel syndrome (IBS). IBS is associated with persistent disorders of bowel motility. The symptoms are triggered by changes in the properties of enteric neurons, many of which become hyperexcitable. Enteric neurons are part of the nervous system within the gut wall. However, the neurons that have changed properties after inflammation have not been identified, and the mechanisms of change are not known. This work is designed to determine the molecular basis of the changes in neuron excitability that lead to hyperexcitability. Identification of the molecules whose properties are changed will permit those molecules to be targeted in the design of compounds to treat the abnormalities of intestinal physiology that follow inflammation.Read moreRead less