Investigation Of Neural Mechanisms Of 670 And 830nm Laser Acupuncture In Pain Relief, Using Rat
Funder
National Health and Medical Research Council
Funding Amount
$326,207.00
Summary
Background Chronic pain is common and costs $10 billion dollars per year in Australia. Drug therapies are widely used but serious side effects limit use. Patients actively seek non-drug treatments and laser acupuncture is one of the most commonly sought therapies for chronic pain, however, how it works is not well understood. Our previous work Researchers propose that laser acupuncture reduces pain by direct effects on nerves, altering how pain signals are transmitted to the brain. To investigat ....Background Chronic pain is common and costs $10 billion dollars per year in Australia. Drug therapies are widely used but serious side effects limit use. Patients actively seek non-drug treatments and laser acupuncture is one of the most commonly sought therapies for chronic pain, however, how it works is not well understood. Our previous work Researchers propose that laser acupuncture reduces pain by direct effects on nerves, altering how pain signals are transmitted to the brain. To investigate this we (CI A and CI B) previously undertook a study of infrared laser on nerve cell cultures. This followed on from a positive clinical study with the same laser wavelength in the treatment of neck pain, undertaken by CI B. We established that laser temporarily interrupts the nerve transport system, which is made up of a series of minute tubes, called microtubules. These act as a “monorail” system for transport of mitochondria, which provide energy for all nerve functions. We propose that temporary interruption of this system, called fast axonal transport, disrupts the conduction of pain signals along the nerve, resulting in pain relief. Important unanswered questions The mechanism by which 830nm laser acupuncture relieves pain clinically remains poorly understood. For its acceptance into mainstream clinical practice it is important to determine the effect of laser on the peripheral nerves and in particular the pain carrying fibres. We know from an earlier study that a single exposure causes significant but reversible changes in pain fibres including axonal microtubule disruption, decrease in mitochondrial membrane potential and block of fast axonal flow. These events would result in conduction failure. The question is whether the repeated irradiations, comparable to those delivered clinically result in the same changes. This would provide a scientific basis for understanding the clinical effectiveness of laser acupuncture. We also do not know if 670nm laser acupuncture would act in the same way. There is evidence that this may be more effective so that this remains another important unanswered question. Further, there is no evidence regarding which wavelength would be cost and time effective as it is desirable to deliver lower dose. We need to determine the most effective dose and wavelength so that clinical trials could be carried out as was done for the trials by CIB (Chow and Barnsley, 2006).Read moreRead less
Assembly And Misassembly Of Mitochondrial Respiratory Chain Complex I
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Mitochondria are the powerhouses in our cells. They burn the carbon fuels we eat and store the energy by making ATP that is used for functions such as muscle contraction and triggering of nerves. Mitochondrial Complex I is a molecular motor that helps to make ATP. “Mitochondrial disease” is often seen when Complex I is not built properly and this results in early childhood death. In this project we will study how Complex I is built and how the mitochondria responds to assembly problems.
STRUCTURE, FUNCTION AND REGULATION OF F-TYPE ATP SYNTHASES
Funder
National Health and Medical Research Council
Funding Amount
$544,660.00
Summary
ATP synthase is the molecular machinery that converts energy derived from nutrients or photosynthesis into the universal biological energy carrier ATP (adenosine triphosphate). This is one of the most fundamental processes of life and is conserved from bacteria to plants to humans. Understanding how bacterial and mitochondrial ATP synthases work in molecular detail will have wide-ranging implications for both medicine (in understanding metabolic disorders, controlled cell death and aging) and th ....ATP synthase is the molecular machinery that converts energy derived from nutrients or photosynthesis into the universal biological energy carrier ATP (adenosine triphosphate). This is one of the most fundamental processes of life and is conserved from bacteria to plants to humans. Understanding how bacterial and mitochondrial ATP synthases work in molecular detail will have wide-ranging implications for both medicine (in understanding metabolic disorders, controlled cell death and aging) and the design of new antibacterial agents.Read moreRead less
Systems Approaches To Understanding Mitochondrial Function And Dysfunction In Disease
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Mitochondria produce the energy for our bodies. Defects in this process cause mitochondrial disease, which affects at least 1/4300 people. Diagnosis is often inconclusive and few if any effective treatments exist. State of the art CRISPR gene-editing tools will be used to make disease models mimicking the different types of mitochondrial disease. These will be used to understand how mitochondria function, identify new disease genes and develop new drugs.
Mitochondria are both the powerhouses and the poison cupboard of our cells. They have evolved from bacteria and still possess the ability to grow and divide. Unregulated mitochondrial division is seen in dying cells and in cells from patients with neurodegenerative diseases. We have identified new molecules involved in mitochondrial division and are investigating how they function in normal and unhealthy cells.
Understanding Uterine Contractility: What Can We Learn From Obesity?
Funder
National Health and Medical Research Council
Funding Amount
$600,792.00
Summary
The incidence of failure to progress in labour has increased in recent years, being linked to the rise in obesity. The result is a significant escalation in the rate of delivery by Caesarean Section (CS) which increases the risk of serious complications during subsequent pregnancies. We have identified five dysfunctional systems associated with poor uterine contraction. We now aim to determine the mechanisms underlying these dysfunctional systems, particularly those mechanisms in common.
EPITHELIAL ION TRANSPORT DEFECTS IN CYSTIC FIBROSIS: PATHOPHYSIOLOGY AND TREATMENT
Funder
National Health and Medical Research Council
Funding Amount
$290,440.00
Summary
The thin layer of fluid covering the surface of the air passages acts to protect the airway surface from drying. This fluid also allows the hair-like projections, or cilia, on the top of the airway cells to beat more effectively. The volume and composition of this fluid is determined by the movement of salt and water across the mucous membranes of the air passages. The importance of this fluid is shown by the problems that occur in Cystic Fibrosis (CF), the most common lethal inherited disease a ....The thin layer of fluid covering the surface of the air passages acts to protect the airway surface from drying. This fluid also allows the hair-like projections, or cilia, on the top of the airway cells to beat more effectively. The volume and composition of this fluid is determined by the movement of salt and water across the mucous membranes of the air passages. The importance of this fluid is shown by the problems that occur in Cystic Fibrosis (CF), the most common lethal inherited disease affecting Australians. In CF, altered salt transport causes drying of the airway surface which impairs the working of the cilia. This leads to retention of mucous in the airway with repeated bacterial infections damaging the lungs. Simple tests have been designed to directly measure the movement of salt across the surface of the nasal passage using a fine soft rubber tube. Movement of mucous in the nose is measured using other simple techniques that are currently used diagnostically. Together, these tests in the nose provide vital information about how the surface of normal human airway moves salt, water and mucous. Any differences found in CF patients will then give us a good idea of the problems found in the CF lung. We will study the interactions between calcium, sodium and chloride in the fluid lining the airways, measuring changes in salt and mucous movement. A range of testing procedures will be used in human volunteers, anaesthetised mice and isolated tissues from sheep. We have already demonstrated important links between the fluid lining the airways and salt movement, and we expect that this may lead to the development of new treatments for Cystic Fibrosis. This therapy will focus on treating the lung problems of CF patients, the major cause of disability. We anticipate that this preventative therapy may offer real benefits in the fight to cure CF.Read moreRead less
Fission, Fusion And Distribution Of Mitochondria In Mammalian Cells
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
Mitochondria are small cellular compartments that produce most of the cell's energy in the form of ATP. Mitochondria were once thought of as small bean-shaped organelles floating around in the cell, however it has become clear that this is not the case. Mitochondria are found as a network of tubules radiating from around the nucleus and they undergo constant changes in their shape through both fission and fusion events. Mitochondria are transported along microtubules which act as highways in the ....Mitochondria are small cellular compartments that produce most of the cell's energy in the form of ATP. Mitochondria were once thought of as small bean-shaped organelles floating around in the cell, however it has become clear that this is not the case. Mitochondria are found as a network of tubules radiating from around the nucleus and they undergo constant changes in their shape through both fission and fusion events. Mitochondria are transported along microtubules which act as highways in the cell so that they can be distributed to areas that require ATP or other functions particular to mitochondria such as their ability to regulate the release of calcium. In specialist cells, mitochondria are organised even further. Sperm cells contain mitochondria packed around the mid-piece of the flagellum so that ATP can be utilised directly for swimming. Mitochondria are also highly organised in muscle cells to supply ATP for movement while in pancreatic cells mitochondria at the cell's edge help to regulate the secretion of molecules such as insulin into the bloodstream. While we are beginning to understand the great importance of mitochondria to the cell, we are yet to work out how these organelles undergo the drastic morphological changes which are essential for cellular function. In this application, we plan to identify and characterise the proteins involved in the division of mitochodria and the movement of these organelles along the microtubule highways. Understanding the basic mechanisms of mitochondrial dynamics in tissue culture cells will provide valuable insights into mitochondrial segregation and specialisation in differentiated cells such as sperm, nerve, muscle and pancreatic cells, where such events are crucial for function.Read moreRead less