Neural Mechanisms Mediating Hypersecretion And Motility Patterns Induced By Enterotoxins
Funder
National Health and Medical Research Council
Funding Amount
$415,250.00
Summary
This project aims to identify the nerve cells that are responsible for the massive oversecretion of water and salt seen with cholera and other diseases producing diarrhoea. Many of these disease act through specific toxins and, although the biochemical targets of these toxins are reasonably well understood, the nerve cells on which they act have never been identified. Furthermore, the mechanisms that couple the oversecretion with a massive increase in the propulsive activity of the intestine are ....This project aims to identify the nerve cells that are responsible for the massive oversecretion of water and salt seen with cholera and other diseases producing diarrhoea. Many of these disease act through specific toxins and, although the biochemical targets of these toxins are reasonably well understood, the nerve cells on which they act have never been identified. Furthermore, the mechanisms that couple the oversecretion with a massive increase in the propulsive activity of the intestine are also unknown. We will investigate each of these questions using the small intestine of the guinea-pig, because the nerve circuit in this preparation is better understood than that of any other. Nerve cells that respond to three specific toxins, each known to activate the nervous system via different mechanisms, will be determined using intracellular recording methods, injection of marker dyes and methods that allow the identification of their neurochemistry. This will allow the functions of responsive nerve cells to be identified and their places in the circuits that control secretion and propulsion to be determined. This information will be correlated with studies in whole animals being undertaken in Sweden so that potential sites for intervention can be identified.Read moreRead less
Neural Coordination Of Intestinal Motility And Mucosal Secretion Of Water And Salt - Role In Toxin Induced Diarrhoea
Funder
National Health and Medical Research Council
Funding Amount
$490,020.00
Summary
This project deals with some of the basic mechanisms underlying disorders of gastrointestinal function and in particular with the mechanisms responsible for diarrhoea. Whenever there is a natural disaster (the recent tsunami for example) or a war, the breakdown of medical services leads to concern about outbreaks of cholera and other diarrhoea causing diseases, so understanding the mechanisms by which the cholera bacterium cause diarrhoea remains a major imperative. It is known that the diarrhoe ....This project deals with some of the basic mechanisms underlying disorders of gastrointestinal function and in particular with the mechanisms responsible for diarrhoea. Whenever there is a natural disaster (the recent tsunami for example) or a war, the breakdown of medical services leads to concern about outbreaks of cholera and other diarrhoea causing diseases, so understanding the mechanisms by which the cholera bacterium cause diarrhoea remains a major imperative. It is known that the diarrhoea resulting from cholera infection is produced by an enterotoxin, which acts to produce a massive over-secretion of water and salt through the intestinal wall, which if it is not controlled causes death by dehydration. This effect requires the activity of the nerve cells within the gut wall, the enteric nervous system (ENS). Other bacterial toxins have similar effects and also require activity of the ENS for these effects to be manifested. This project will identify how these toxins alter the activity of the ENS and the effects that they have on intestinal movements which are also regulated by the ENS. We already know that the movements and secretion of water are related to each other and that this relationship is disturbed in some more subtle diseases like irritable bowel syndrome. This project will characterise this relationship, thereby shedding light on the physiology underlying a variety of gastrointestinal disorders.Read moreRead less
Understanding The Role Of MAIT Cells In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$547,593.00
Summary
A specialised set of T lymphocytes called Mucosal Associated Invariant T (MAIT) cells protect us from bacteria and yeast at mucosal sites where the body's immune defences are most easily breached, e.g. gut, oral cavity, airways & reproductive tract. This study investigates the role of MAIT cells in health and in diseases like inflammatory bowel disease, peptic ulceration, periodontitis and tuberculosis. Controlling MAIT cells could help in treating these conditions.
Acupuncture And Mucosal Immunity In The Upper Respiratory Tract
Funder
National Health and Medical Research Council
Funding Amount
$383,082.00
Summary
Many Australians seek complementary and alternate medicine for the treatment of allergic diseases such as allergic rhinitis. There is evidence that acupuncture treatment is clinically beneficial for the treatment of allergic rhinitis. This project will produce new information that will provide a scientific basis of how acupuncture influences the immune response and modulates inflammation. Broader application to other inflammatory diseases and therapeutic interventions is possible.
Coordinating Neuroimmune Sensory Networks In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$884,405.00
Summary
Living organisms use cellular rhythms to optimize their energy use and cellular responses. Our proposal aims to produce significant new fundamental knowledge by elucidating the fundamental cellular and molecular biology of innate cells, their role in mucosal homeostasis and tissue repair pathways in the gut. Understanding this foundational process of cellular regulation will generate new basic knowledge and may lead to better management systems.
Secretion is an essential step in memory and learning, control of metabolism and reproduction and the functioning of most organs. Secretory dysfunction also underlies many diseases including type 2 diabetes. We plan experiments to test for a new model of control of insulin secretion.
Development Of A Novel Mannan-based Avian Influenza Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$195,566.00
Summary
We have a sugar (mannan) that can be used to increase immune responses. We have found that mannan decreases the dose of inactivated virus needed for intranasal immunization. We will investigate if dose sparing is seen when given intramuscularly. This method will be first tried with the human flu virus and if successful will be tried with the bird flu virus. If the preparation can protect mice and ferrets from human or bird flu infection it could develop into a human vaccine against bird flu.
Do Synaptic-like Mechanisms Control Insulin Secretion?
Funder
National Health and Medical Research Council
Funding Amount
$593,235.00
Summary
An estimated 415 million people world-wide were diagnosed with diabetes in 2015. One of the causal factors in disease is the dysregulation of insulin secretion. We have developed new techniques to study insulin secretion that has led us to propose a new model for secretory control. This proposal sets out experiments to critically test this model. The outcomes could have wide-reaching impact on understanding and for future treatment and prevention of the diabetes.