Control Of Gastrointestinal Motility By Interstitial Cells And Neuronal Projections
Funder
National Health and Medical Research Council
Funding Amount
$845,540.00
Summary
The gastrointestinal tract moves contents along its length in an ordered manner, so allowing digestion and absorption of gut contents. These movements are controlled by the properties of the cells in the muscle layers which in part make up the wall of the gastrointestinal tract, by activity in the nerves that innervate the gut and by hormonal factors. Recently we have shown that a key part of the control system lies in a set of special cells, interstitial cells, that lie amongst the muscle cells ....The gastrointestinal tract moves contents along its length in an ordered manner, so allowing digestion and absorption of gut contents. These movements are controlled by the properties of the cells in the muscle layers which in part make up the wall of the gastrointestinal tract, by activity in the nerves that innervate the gut and by hormonal factors. Recently we have shown that a key part of the control system lies in a set of special cells, interstitial cells, that lie amongst the muscle cells. This project will determine how these cells exert their control. These cells generate large long lasting waves of voltage which flow to nearby muscle cells so causing them to contract. The first aim is to determine how the special cells generate the command signals and the second aim is to determine how the signals spread to the muscle cells. The subsequent section of the project will determine how the behavior of the cells in the gastrointestinal tract are controlled by nervous influences. Disorders of the intestine are frequent and these appear to involve disrupted muscle contraction either because the intrinsic control system is malfunctioning or because the nervous system is unable to exert its normal influence. This project will determine how the normal control system works, invariably when this has been done with other systems, disease states are easier to rectify.Read moreRead less
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
Dendritic Activity And Neuronal Output During Sensory Perception
Funder
National Health and Medical Research Council
Funding Amount
$832,748.00
Summary
A fundamental goal of neuroscience is to understand how sensory experiences arise from activity in the brain. This is no easy feat and is the basis of the research in this proposal. Here, using cutting edge recording techniques, the activity of brain cells within the cortex will be measured during sensory-based behavioural tasks. This research will provide insight into therapeutic approaches to numerous brain diseases where sensory processing is compromised.
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.
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
A Signalling Endosomal Network In T Cell Activation
Funder
National Health and Medical Research Council
Funding Amount
$428,016.00
Summary
T lymphocytes play a central role in the adaptive immune response, which specifically targets pathogens and cancer cells and creates the immunological memory. Activation of sometimes as little as one single receptor on a T cell triggers a cellular signal that rapidly expands and branches out in a multitude of sub-signals. Here we will use a combination of novel microscopy approaches to visualise how a network of dedicated intracellular compartments is in charge of these processes.