Imaging The Activation Of Sensory Nerve Endings That Detect Pain In The Colorectum
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
Within the gastrointestinal tract are sensory nerve endings that detect painful stimuli. In this project a new technique has been developed that allows us to monitor and record the activation of the particular sensory nerve endings that detect painful stimuli. This project will determine how these sensory nerve endings detect pain and how drugs might be used to relieve these unpleasant sensations arising from the gut wall.
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.
Importance Of CGRP Alpha In Pain Processing From The Large Intestine
Funder
National Health and Medical Research Council
Funding Amount
$548,289.00
Summary
This project will determine the mechanisms by which sensory nerve endings detect painful stimuli in the large intestine. The project will use a novel genetically modified mouse (that is only available in our laboratory) which allows us, for the first time, to visualize and record directly from the sensory nerve endings that detect painful stimuli and work out how this process occurs. We also identify a specific gene that is essential for detecting painful stimuli from this organ.
Unravelling The Neuropathological Basis Of The Gastrointestinal Manifestations Of Parkinson’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$822,957.00
Summary
Parkinson’s Disease occurs in about 1% of the population. It is a distressing, progressive disease that places a severe burden on patients, families and carers. 80-90% of Parkinson’s Disease patients have constipation which causes substantial distress to patients, their families and carers. We have a rational path to therapy for constipation of Parkinson’s Disease that will be pursued in this project
A Novel Technique For Prolonged Silencing Of Visceral Pain Without Opiates
Funder
National Health and Medical Research Council
Funding Amount
$637,383.00
Summary
There has been substantial interest in the community for pain relief without opiates. This project demonstrates a new strategy to suppress pain at the source for prolonged periods, by suppressing activity in the sensory nerve endings that detect pain, not by acting in central pathways like opiates. To do this, we use a harmless virus to shut down a vital sodium channel for pain perception. These experiments use techniques that were recently developed in our lab and cant be performed elsewhere.
Cell Therapy For Enteric Neuropathies - The Essential Next Steps
Funder
National Health and Medical Research Council
Funding Amount
$667,142.00
Summary
Gastrointestinal motility disorders caused by damage or diseased neurons in the gut wall ("enteric neuropathies) are some of the most clinically challenging conditions to manage because of a lack of effective treatments. Our recent animal studies suggest that cell-based therapies are a real possibility to treat enteric neuropathies. In this project, we will methodically address the outstanding steps that need to be addressed with the aim of moving enteric cell therapies to the clinic.
Role Of Kinesin Binding Protein And Spontaneous Activity In The Development Of Enteric Neurons
Funder
National Health and Medical Research Council
Funding Amount
$599,889.00
Summary
The nerve cells in the wall of the gut play an essential role in motility. Defects in the development of these nerve cells results in pediatric motility disorders. We will examine the roles of two factors, kinesin binding protein, and spontaneous activity in the development of enteric neurons.
Manipulation Of Enteric Neural Stem Cells For Cell Therapy To Treat Enteric Neuropathies
Funder
National Health and Medical Research Council
Funding Amount
$611,438.00
Summary
Cell therapy offers great promise for the treatment of motility disorders due to defects in the nerve cells in the bowel. Patient-derived cells are likely to be the best source of cells, however, patient-derived cells will require manipulation because they are likely to be defective. We will identify manipulations of stem/progenitor cells that increase their efficacy for cell transplantation.
Novel Cell Therapy For Hirschsprung Disease: From Patient IPS Cells To Large Animal Trials
Funder
National Health and Medical Research Council
Funding Amount
$1,011,764.00
Summary
In Hirschsprung disease the lower bowel has no nerve cells. It does not function so it is surgically removed but quality of life is poor. A new idea is to replace the missing cells with new ones. Human infants are very large so we will use new stem cell technologies to create large numbers of cells. We will use polymer chemistry to devise a method of getting the cells into such a large organ as the bowel, and trial these on a model, the piglet, which closely resembles in size the human baby.
Neurons within the wall of the bowel play an essential role in gut motility. A number of motility disorders are caused by diseased enteric neurons, but there are currently no effective treatments for these diseases. We will use animal models of a pediatric motility disorder to examine whether stem cells implanted into the colon can generate neurons and restore normal motility.