I am a neurophysiologist who examines the neural control of movement and the interaction of sensation and movement in human subjects. I study cortical and motoneuronal events during exercise and muscle fatigue. I also study proprioception i.e. the sensati
Origin Of Cells In The 'artificial' Artery Grown In The Peritoneal Cavity
Funder
National Health and Medical Research Council
Funding Amount
$489,000.00
Summary
Implantation of a foreign object (such as a sterile, flexible plastic tube) into the abdominal cavity of animals induces cells floating in the peritoneal fluid to form a capsule around the object. Over the next 2-3 weeks, the cells differentiate into fibroblasts then myofibroblasts. When this capsule of living tissue (in the appropriate moulded shape) is subsequently grafted into smooth muscle-rich organs such as artery, bladder, uterus or vas deferens to replace excised segments, it gains the s ....Implantation of a foreign object (such as a sterile, flexible plastic tube) into the abdominal cavity of animals induces cells floating in the peritoneal fluid to form a capsule around the object. Over the next 2-3 weeks, the cells differentiate into fibroblasts then myofibroblasts. When this capsule of living tissue (in the appropriate moulded shape) is subsequently grafted into smooth muscle-rich organs such as artery, bladder, uterus or vas deferens to replace excised segments, it gains the structure of the surrounding tissue and the myofibroblasts differentiate further into functional smooth muscle. This raises the question: what is the origin of the cells of the capsule? Our previous studies suggested that monocyte-macrophages stimulated to enter the abdominal cavity in response to the sterile foreign body might be the source of the cells. In the current study we will use transgenic (c-fms EGFP and c-fms Cre Z-AP) mice in which cells of monocyte-macrophage lineage are genetically labelled. These cells can be clearly distinguished from all other cells of the body, and analysis of capsules formed around foreign bodies will give us a definitive answer. We will using micro-array analysis, determine which growth factors-cytokines are important in regulating differentiation of the cells, and the role of physical factors (eg pulsatile stretching). Finally, we will determine whether these cells stimulated to enter the abdominal cavity are capable of differentiating along alternative pathways, such as cardiac muscle or liver cells. Knowledge gained will further the use of the abdominal cavity as a bioreactor in which to engineer tissues for organ replacement therapies. Identification of the mechanisms regulating the (trans)differentiation and biology of the cells may also assist in wound repair strategies to prevent pathologies caused by excessive myofibroblast accumulation and fibrosis.Read moreRead less
Brain Plasticity Following Changes In Sensory Input
Funder
National Health and Medical Research Council
Funding Amount
$312,576.00
Summary
The research proposed here will investigate the mechanisms our brains use to adapt to changes in sensory input, as occurs following blindness, deafness, nerve damage or loss of a limb. The information gathered will help develop treatments for diseases associated with sensory loss, as well as those associated with deficits in our ability to learn and remember, such as Alzheimer's disease.
Synaptic Integration And Plasticity In The Rat Piriform Cortex
Funder
National Health and Medical Research Council
Funding Amount
$250,500.00
Summary
The human cerebral cortex is the pinnacle of evolution. It is the most complex structure known, responsible for all of those skills - like language and reasoning - that make our species so remarkable. It is also a major site of many brain diseases, like schizophrenia and epilepsy. An understanding of how the cerebral cortex works would be a remarkable achievement, of immeasurable benefit to human health. How can one go about studying such a complex structure? The strategy taken in this project i ....The human cerebral cortex is the pinnacle of evolution. It is the most complex structure known, responsible for all of those skills - like language and reasoning - that make our species so remarkable. It is also a major site of many brain diseases, like schizophrenia and epilepsy. An understanding of how the cerebral cortex works would be a remarkable achievement, of immeasurable benefit to human health. How can one go about studying such a complex structure? The strategy taken in this project is to begin by studying one of the simplest regions of the cerebral cortex, the olfactory (or piriform) cortex. The olfactory cortex is an evolutionarily ancient region of cortex, with a simpler architecture than other cortical regions. Its task is to process the sense of smell, a primitive sense that is more elaborated in lower animals than in humans. The broad goal of our research is to understand, by studying the olfactory cortex of rats, how olfactory processing occurs at the level of nerve cells (neurons). We will use a number of powerful techniques - including microelectrode recording and laser microscopy - to measure the electrical properties of individual neurons. We will also study the synaptic connections between neurons, and how these connections change following memory-inducing stimuli. It is hoped that this work will shed light on how the healthy cortex is able to process and store information, and how brain diseases cause these functions to deteriorate.Read moreRead less
I am a physiologist investigating the molecular basis of normal function in skeletal muscle and the dysfunctions occurring in various muscle diseases and in fatigue. In addition, I investigate analogous dysfunction of calcium release and excitability occu
Establishing STARS As A Therapeutic Target To Reduce Muscle Wasting And Improve Muscle Function
Funder
National Health and Medical Research Council
Funding Amount
$446,189.00
Summary
Muscle wasting occurs rapidly with disuse after injuries occurring at work, during sport, with chronic disease and in road accidents. It is also a consequence of ageing. Muscle wasting and reduced muscle function places considerable financial strain on our health care system. We aim to use gene therapy and pharmacological interventions to increase the levels of a protein called STARS. We hypothesize that STARS will reduce disuse-induced muscle wasting, increase recovery and improve function.
Genetic Basis For Skeletal Muscle Formation And Regeneration In Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$876,005.00
Summary
How does muscle grow and repair after injury or disease? This basic question in the focus of the research in this fellowship. Specific cells are put aside during development to generate the growth and provide stem cells required for regeneration. Using the advantages of the zebrafish system I will record the action of different stem cell populations during growth and disease. I will define the genes required for stem cell action and utilize this knowledge to create new therapeutic pathways.
Therapeutic Potential Of Skeletal Muscle Plasticity And Slow Muscle Programming For Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$780,476.00
Summary
There is no cure for DMD, a devastating, life-limiting muscle disease causing progressive muscle wasting in boys and young men. A potential therapy may come from modulating muscle activity patterns to promote a protective slow muscle phenotype through low-frequency stimulation protocols and/or well-described pharmacological ‘exercise mimetics’. This proposal will evaluate their therapeutic merit in mouse models of DMD to answer the key questions to advance this approach to the clinic.