Targeting GDNF Family Ligand (GFL) Signalling To Treat Inflammatory Bone Pain
Funder
National Health and Medical Research Council
Funding Amount
$329,285.00
Summary
Pain associated with bone marrow oedema syndromes, osteomyelitis, osteoarthritis, fractures and bone cancer causes a major burden on individuals and health care systems in Australia and worldwide. In this application, we will explore specific signalling pathways that we have identified in nerves that code bone pain. This will provide an opportunity for the rational design of highly specific drugs capable of interacting exclusively with molecules that drive pain in these conditions.
Differentiation, Electrical Activity And Synapse Structure Of Human Stem Cell-derived Sensory Neurons
Funder
National Health and Medical Research Council
Funding Amount
$322,088.00
Summary
A major challenge in treating neurodegenerative conditions with stem cells, is to generate a population of donor cells which are capable of incorporating into the host nervous system and restoring function. This proposal will test the capacity of human stem cells to make functional connections in the auditory system, potentially enhancing hearing with a cochlear implant. These studies are critical in determining how stem cells may be used to promote functional regeneration of the damaged nervous ....A major challenge in treating neurodegenerative conditions with stem cells, is to generate a population of donor cells which are capable of incorporating into the host nervous system and restoring function. This proposal will test the capacity of human stem cells to make functional connections in the auditory system, potentially enhancing hearing with a cochlear implant. These studies are critical in determining how stem cells may be used to promote functional regeneration of the damaged nervous system.Read moreRead less
Use Of A Novel Technique To Identify The Sensory Nerve Endings That Respond To Painful Stimuli In The Upper Gastrointestinal Tract And Characterize Their Mechanisms Of Activation
Funder
National Health and Medical Research Council
Funding Amount
$353,243.00
Summary
Many people experience pain in their upper gastrointestinal tract. Unlike the skin, however, we have no idea where the sensory nerve endings that detect pain are located in this part of the body, and no clear understanding of how these nerve endings are activated to cause pain. This project will utilise a novel technique recently developed by the CIA to finally identify and record directly from the sensory nerve endings that detect painful stimuli in the upper gastrointestinal tract and characte ....Many people experience pain in their upper gastrointestinal tract. Unlike the skin, however, we have no idea where the sensory nerve endings that detect pain are located in this part of the body, and no clear understanding of how these nerve endings are activated to cause pain. This project will utilise a novel technique recently developed by the CIA to finally identify and record directly from the sensory nerve endings that detect painful stimuli in the upper gastrointestinal tract and characterise the mechanisms underlying their activation.Read moreRead less
Understanding How Inflammatory Bowel Disease Causes Hypersensitivity Of Colonic Sensory Nerve Endings And Increased Abdominal Pain
Funder
National Health and Medical Research Council
Funding Amount
$589,466.00
Summary
Patients with inflammatory bowel disease (IBD) commonly experience increased abdominal pain. This project utilises two novel techniques developed by the Chief investigator, that allow us to understand how inflammation of the large intestine leads to increased pain sensations. This project will use these new techniques to identify, for the first time, the sensory nerve endings that detect painful stimuli from within the large intestine; and how these nerve endings become hyperexcitable during inf ....Patients with inflammatory bowel disease (IBD) commonly experience increased abdominal pain. This project utilises two novel techniques developed by the Chief investigator, that allow us to understand how inflammation of the large intestine leads to increased pain sensations. This project will use these new techniques to identify, for the first time, the sensory nerve endings that detect painful stimuli from within the large intestine; and how these nerve endings become hyperexcitable during inflammation to cause increased abdominal pain.Read moreRead less
Role Of Sensory Neurons In Obstruction-induced Bladder Overactivity
Funder
National Health and Medical Research Council
Funding Amount
$340,986.00
Summary
About 20% of people over the age of 40 have the clinical syndrome of an “overactive bladder”, which causes symptoms of urgency, frequency and incontinence. The mechanisms causing bladder overactivity are not known. This project will identify sensory neurons, which become overexcited, and determine which mediators and ionic channels are responsible for this. Our new data will identify selective pharmacological targets for new therapies and diagnostic tools for these distressing bladder disorders.
Transcriptional Regulation Of Nociceptor Function And Extreme Genetic Pain Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,007,462.00
Summary
Disorders involving untreatable pain have a devastating impact on a patient’s quality of life. To better treat these conditions, we require a basic understanding of how sensory neurons work. In this study we will define the genetic network involved in regulating pain-sensing neurons. We will then search the genome of pain patients looking for coding mutations within this pain transcriptional network, and we will prove these mutations are causative in fly and mouse systems.
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.
Analysis Of Functional Role Of The BDNF Precursor In Sensory Neurons
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
Neurotrophins, which are generated from their precursors, are essential for the survival and function of the nervous system. One of neurotrophins, brain derived neurotrophic factor (BDNF), is made in sensory neurons and transported towards nerve terminals. Mutation of a single amino acid in the precursor of BDNF disrupts this transport. This project will examine whether the precursor of BDNF has any function within sensory nerves. We will examine whether the precursor of BDNF gets into the nerve ....Neurotrophins, which are generated from their precursors, are essential for the survival and function of the nervous system. One of neurotrophins, brain derived neurotrophic factor (BDNF), is made in sensory neurons and transported towards nerve terminals. Mutation of a single amino acid in the precursor of BDNF disrupts this transport. This project will examine whether the precursor of BDNF has any function within sensory nerves. We will examine whether the precursor of BDNF gets into the nerve via its receptors and whether it plays any role in the development of pain and maintenance of neuropathic pain after nerve injury. Successful execution of the project will eludicate mechanisms of pain, especially neuropathic pain, and will provide important information to assist in the design of drugs for neurological diseases.Read moreRead less
Mechanisms Of Activation Of Vascular Afferent Nociceptors To The Gut
Funder
National Health and Medical Research Council
Funding Amount
$542,890.00
Summary
We have recently identified the nerve fibres responsible for detecting pain from the gut. In this project we will study exactly how these nerve cells are activated by movements of the gut wall, by changes in blood vessel diameter and how this can be studied most efficiently We will use this information to develop simple preparations in which to study these sensory nerves in animal and adult tissue to test which drugs may affect their excitability and hence be useful in treating gut pain.
The broad aim of this project is to understand how the eye receives visual signals and sends them to the brain. Our experimental goal is to study the structure of neural connections in a poorly understood division of the visual system, called the koniocellular pathway. The cells of the koniocellular pathway make up close to 10 percent of all projections from the eye to the brain, but their functions are almost completely unknown. The fovea is a specialised region of the retina (the nerve cells w ....The broad aim of this project is to understand how the eye receives visual signals and sends them to the brain. Our experimental goal is to study the structure of neural connections in a poorly understood division of the visual system, called the koniocellular pathway. The cells of the koniocellular pathway make up close to 10 percent of all projections from the eye to the brain, but their functions are almost completely unknown. The fovea is a specialised region of the retina (the nerve cells which line the back of the eye). It is characterised by a very high density of cone photoreceptors, and is essential for high-acuity vision. This makes the fovea the most important part of the primate retina, but the high density of nerve cells there is thought to be the reason why the fovea is especially vulnerable to disease and age-related degeneration. Our aim is to analyse, using high-resolution microscopic techniques, the connections of koniocellular-pathway cells within the retina. We specifically aim to discover whether the koniocellular pathway contributes to foveal vision. Recent work from our and other laboratories has shown that many koniocellular-pathway cells receive functional connections from short-wavelength sensitive (blue) cone photoreceptors. Thus, our study will provide new insights into the connectivity of blue-cone pathways in the fovea. Although these experiments address basic scientific questions, they can lead to improved clinical practice. Understanding the wiring diagram of the retina can inform clinical studies of conditions such as glaucoma, and helps to give a rational basis for development of treatments. For example, dysfunction in blue-cone pathways is an early sign of glaucoma, so understanding the connections of blue-cone pathways in the fovea can lead to improved methods for early detection of this leading cause of blindness.Read moreRead less