"Smart Food" - The fulcrum in the energy balance equation. The overall aim of the project is to establish how nutrients best promote an increase in energy expenditure and therefore weight loss. The experiments will be performed in rats using sophisticated technologies to introduce specific combinations of fats, carbohydrates or proteins directly into the stomach and then measure energy expenditure in a specialised type of energy burning rather than energy storing fat called brown adipose tissue. ...."Smart Food" - The fulcrum in the energy balance equation. The overall aim of the project is to establish how nutrients best promote an increase in energy expenditure and therefore weight loss. The experiments will be performed in rats using sophisticated technologies to introduce specific combinations of fats, carbohydrates or proteins directly into the stomach and then measure energy expenditure in a specialised type of energy burning rather than energy storing fat called brown adipose tissue. These experiments will uncover the mechanisms that relate nutrients in the stomach and activation of brown adipose tissue. They will provide a framework on which this project can build a knowledge of smart diets that will allow the effective control of body weight through modulation of energy expenditure. Read moreRead less
Mechanisms Underlying Disordered Skin Blood Flow Following Nerve Injury
Funder
National Health and Medical Research Council
Funding Amount
$408,000.00
Summary
Many people who recover from traumatic injury or who have chronic conditions such as diabetes or neuropathy from exposure to a toxic chemical suffer from peripheral vascular disorders leading to poor circulation in the extremities. These conditions are characterised by impaired wound healing, cold hands and feet and ongoing pain. These people must face a long life with progressively increasing disability. Even normal ageing can lead to similar problems. This project is directed at understanding ....Many people who recover from traumatic injury or who have chronic conditions such as diabetes or neuropathy from exposure to a toxic chemical suffer from peripheral vascular disorders leading to poor circulation in the extremities. These conditions are characterised by impaired wound healing, cold hands and feet and ongoing pain. These people must face a long life with progressively increasing disability. Even normal ageing can lead to similar problems. This project is directed at understanding the role of the nerve supply to blood vessels in the skin in these disorders. The experiments will be conducted in skin blood vessels of rats with various forms of nerve lesion that will mimic these conditions in patients. We will use our knowledge of the structure and behaviour of nerve-blood vessel connections to analyse the changes in the properties of vascular smooth muscle and relate it to the state of the innervation. Skin arteries normally receive two types of nerve - sympathetic (which release noradrenaline) and afferent ( which release peptides) - that have opposing actions on the vessel (constriction and dilation respectively). We hypothesize that removal of part or all of the innervation changes the contractile mechanism of the smooth muscle in the wall of the vessel so that it becomes much more sensitive to calcium ions and produces larger and more prolonged contractions. We will combine electrophysiology and contraction studies with immunohistochemistry and biochemical analysis to define the relation between the nerve deficit and the vascular responses. The aim is to identify appropriate drug targets for which local application in the affected region can alleviate the symptoms without causing widespread side effects.Read moreRead less
Anandamide activated chloride channels in sensory neurons. We are seeking to understand how the nerve cells that sense our environment are regulated by signalling molecules produced by our body. Understanding how these cells function in normal conditions is essential as basis for understanding how they may function abnormally in physically stressful situations or in chronic pain conditions. The work may eventually lead to better treatments for a wide range of disorders that involve the sensory ....Anandamide activated chloride channels in sensory neurons. We are seeking to understand how the nerve cells that sense our environment are regulated by signalling molecules produced by our body. Understanding how these cells function in normal conditions is essential as basis for understanding how they may function abnormally in physically stressful situations or in chronic pain conditions. The work may eventually lead to better treatments for a wide range of disorders that involve the sensory nervous system. Read moreRead less
The role of intracellular calcium in fibre-type specific gene expression in skeletal muscle. Muscles contain different fibre types whose composition can be changed by activity. The aim of this proposal is to identify the intracellular mechanisms which control fibre type. Our hypothesis is that different patterns of intracellular calcium determine the pattern of gene expression which determines fibre type. Understanding how gene expression is regulated is a central issue in biology.
Chemotherapy-induced Peripheral Neuropathy In The Pediatric Population: Risk Factors, Assessment Strategies And Functional Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$88,766.00
Summary
Chemotherapy, commonly used for treatment of childhood cancer, can cause peripheral nerve injury with disabling symptoms which may be long lasting. This project aims to provide a comprehensive evaluation of the nerve injury and standardize sensitive ways of measuring nerve function. This is the first study that will follow children throughout their treatment cycle with regular nerve assessments, providing a greater understanding of nerve injury mechanisms and enabling treatment modification.
Novel Applied Bayesian Statistics for Monitoring Neuromuscular Diseases. Neurological diseases such as motor neurone disease are caused by the progressive death of motor units serving a muscle. Currently there are no ways of quantifying and detecting change in the number of motor units serving a muscle which are non-invasive. Our research will provide an objective method for the progression of neuromuscular diseases to be monitored with minimal inconvenience to patients. This will allow clinic ....Novel Applied Bayesian Statistics for Monitoring Neuromuscular Diseases. Neurological diseases such as motor neurone disease are caused by the progressive death of motor units serving a muscle. Currently there are no ways of quantifying and detecting change in the number of motor units serving a muscle which are non-invasive. Our research will provide an objective method for the progression of neuromuscular diseases to be monitored with minimal inconvenience to patients. This will allow clinical trials for possible effective treatments of neurological diseases such as motor neurone disease to be conducted with an objective measurement of disease progression. Read moreRead less
Clinical Features, Neurophysiology And Histopathology Of Peripheral Neuropathy In Children With Mitochondrial Disease
Funder
National Health and Medical Research Council
Funding Amount
$56,200.00
Summary
Peripheral neuropathies are frequently associated with mitochondrial diseases in children and cause progressive weakness and gait abnormalities and could result in loss of ambulation. This study aims to characterise the clinical spectrum and range of electrophysiological and histopathological abnormalities in the peripheral nerves of children with mitochondrial neuropathies to provide a resource that enables early diagnosis and implementation of rehabilitative measures.
The Biophysical Basis Of HCN Channels In Human Peripheral Nerve
Funder
National Health and Medical Research Council
Funding Amount
$50,315.00
Summary
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play an important role as pacemakers in the cardiac and nervous systems. HCN channel dysfunction is implicated in a number of disorders including neuropathic pain and epilepsy. My aim is to determine the kinetics and voltage dependence of HCN channels in human peripheral nerve in vivo. Understanding these channels is a prerequisite to the development of safe targeted therapies against neuropathic pain.
Use of an animal model to understand mechanisms underlying reductions in body weight associated with use of the laparoscopic adjustable gastric band. At least one in ten Australians is classified as morbidly obese and as such are eligible for bariatric surgery. Those undergoing the surgery will achieve an average excess weight loss of up to 60 per cent, they will have reduced or eliminated diabetes and will appreciably improve their prospects of survival. These experiments aimed at understandin ....Use of an animal model to understand mechanisms underlying reductions in body weight associated with use of the laparoscopic adjustable gastric band. At least one in ten Australians is classified as morbidly obese and as such are eligible for bariatric surgery. Those undergoing the surgery will achieve an average excess weight loss of up to 60 per cent, they will have reduced or eliminated diabetes and will appreciably improve their prospects of survival. These experiments aimed at understanding the mechanisms underpinning this success have the potential to further improve surgical approaches and outcomes and provide insights that will better enable weight loss therapies for all overweight and obese Australians.Read moreRead less
Discovering Genes For X-linked Charcot-Marie-Tooth Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$486,789.00
Summary
Our goal is to explore peripheral nerve degeneration by identifying the genes causing X-linked forms of Charcot-Marie-Tooth neuropathy. Using bioinformatic resources, next generation sequencing and state of-the-art microarray and mutation scannning technologies we will perform comprehensive systematic analysis of candidate genes on the X chromosome. Discovery of genes for this subset of inherited peripheral neuropathies will elucidate mechanisms causing neurodegeneration and lead to targeted the ....Our goal is to explore peripheral nerve degeneration by identifying the genes causing X-linked forms of Charcot-Marie-Tooth neuropathy. Using bioinformatic resources, next generation sequencing and state of-the-art microarray and mutation scannning technologies we will perform comprehensive systematic analysis of candidate genes on the X chromosome. Discovery of genes for this subset of inherited peripheral neuropathies will elucidate mechanisms causing neurodegeneration and lead to targeted therapeutic treatment strategies.Read moreRead less