Role Of Microbiota In The Developing Enteric Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$661,979.00
Summary
The correct development of neurons in the gut is vital for digestive functions. This project will provide novel insights into how environmental factors such as the bacteria that reside in the gut and changes in diet affect maturation of the gut’s nervous system. The data will improve knowledge of the effects of widely used antibiotics and probiotics, which will facilitate strategies to improve human health and quality of life.
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
The Physiological And Pathological Role Of The Bile Acid Receptor TGR5 And Its Potential Targeting For The Treatment Of Intestinal Motility Disorders And Visceral Pain.
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
Defects in the secretion of bile into the intestine cause digestive diseases, and abnormal circulating levels of bile acids induce profound itch and abnormal pain sensation. This project examines whether a cell-surface receptor (TGR5) produced by intestinal and sensory neurons mediates actions of bile acids on intestinal functions and pain. The project aims to define mechanisms of digestive and sensory disorders and identify new therapies for constipation, diarrhoea, and pain.
Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occul ....Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occult segmental pattern in adult mice. This work will give us a new way of understanding the organisation of brainstem centres that control breathing, cardiovascular functions and emotional states.Read moreRead less
How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information i ....How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information is essential to understand how blood pressure is controlled under healthy conditions.Read moreRead less
Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also mi ....Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also migratory cell populations that must populate the areas through which they migrate, and thus some cells get left behind while others advance. The planned data are likely to be relevant to other cell populations that also populate the areas through which they migrate, including neural crest-derived melanocytes and Schwann cell precursors.Read moreRead less
Electrical activity in early enteric neuron development. Intestinal movements and secretion are critical to the good health and nutrition of both humans and animals. These functions are regulated by a large nervous system contained within the intestinal wall, the enteric nervous system. This project will identify how enteric nerve cells develop and how their behaviour influences the development of other enteric nerve cells. This is will provide an important base for more applied research aime ....Electrical activity in early enteric neuron development. Intestinal movements and secretion are critical to the good health and nutrition of both humans and animals. These functions are regulated by a large nervous system contained within the intestinal wall, the enteric nervous system. This project will identify how enteric nerve cells develop and how their behaviour influences the development of other enteric nerve cells. This is will provide an important base for more applied research aimed at developing treatments for diseases like chronic constipation and irritable bowel syndrome. It will also contribute to the growing knowledge about how epigenetic factors can modify genetically programmed development within the nervous system.Read moreRead less
Cell cycle and enteric neuron and glial differentiation. Enteric neurons arise from a very small starting population of precursor (neural crest) cells, most of which emigrate from the hindbrain, and colonise the developing gut. Over a protracted period of time the precursors proliferate and differentiate into glia and many different types of neurons. Cell cycle exit is a critical event in the development of many neuron types, largely because the time at which cells exit from the cell cycle lim ....Cell cycle and enteric neuron and glial differentiation. Enteric neurons arise from a very small starting population of precursor (neural crest) cells, most of which emigrate from the hindbrain, and colonise the developing gut. Over a protracted period of time the precursors proliferate and differentiate into glia and many different types of neurons. Cell cycle exit is a critical event in the development of many neuron types, largely because the time at which cells exit from the cell cycle limits the number of neurons that will be generated. We will determine whether exit from the cell cycle contributes to the differentiation and specification of enteric neurons and glia.Read moreRead less
Cellular bases of enteric neural circuitry underlying gut propulsion. This project aims to investigate the neural bases of behaviour in the mammalian gut. The Enteric Nervous System (ENS) plays a critical role in the propulsion of intestinal contents. This project expects to establish how specific functional classes of enteric neurons control propulsion along the gut. By recording the simultaneous neural activity from hundreds of different functional classes of enteric nerve cells simultaneously ....Cellular bases of enteric neural circuitry underlying gut propulsion. This project aims to investigate the neural bases of behaviour in the mammalian gut. The Enteric Nervous System (ENS) plays a critical role in the propulsion of intestinal contents. This project expects to establish how specific functional classes of enteric neurons control propulsion along the gut. By recording the simultaneous neural activity from hundreds of different functional classes of enteric nerve cells simultaneously, whilst recording intestinal muscle electrical activity and the movements of the gut wall, the project expects to identify which enteric neurochemical classes of neurons generate specific motor patterns along the intestine.Read moreRead less
The jugular vagal sensory connectome regulating visceral function. Internal body organs have a rich supply of sensory nerve fibres that serve important roles in monitoring the local environment for normal and abnormal sensory stimuli. These nerve fibres have different origins and wire into brain circuits that regulate widely diverse physiological responses. In this study we aim to study the neural circuits and responses mediated by a group of these sensory nerves which has not been investigated ....The jugular vagal sensory connectome regulating visceral function. Internal body organs have a rich supply of sensory nerve fibres that serve important roles in monitoring the local environment for normal and abnormal sensory stimuli. These nerve fibres have different origins and wire into brain circuits that regulate widely diverse physiological responses. In this study we aim to study the neural circuits and responses mediated by a group of these sensory nerves which has not been investigated appreciably in the past. We believe that these sensory neural circuits will reveal important new insights into how internal organs perform their diverse and essential functions to sustain life.Read moreRead less