Functional Electrical Stimulation Assisted Cycling (eStimCycle):A Novel Intervention To Improve Outcomes In The Critically Ill
Funder
National Health and Medical Research Council
Funding Amount
$868,811.00
Summary
The legacy of critical illness leaves millions of survivors worldwide with long lasting deficits in physical and brain function as well as anxiety, depression and post-traumatic stress disorder. Early rehabilitation may prevent or minimise these effects. This study evaluates the effectiveness of functional electrical stimulation of muscles with assisted in-bed cycling (eStimCycle) on muscle bulk, strength, physical and brain function at hospital discharge, 6 and 12 months.
Rescuing The Dystrophin-glycoprotein Complex To Protect Muscles From Wasting Conditions
Funder
National Health and Medical Research Council
Funding Amount
$833,340.00
Summary
Existing medical strategies to counteract severe muscle wasting disorders are compromised because of dysfunctional signalling around a cluster of proteins called the dystrophin-glycoprotein complex (DGC) located at the muscle membrane. To address this significant unmet medical need, this proposal investigates novel approaches to retain or restore DGC integrity at the muscle membrane with the goals of preserving and protecting muscles during serious wasting conditions.
Long-term Effects Of Very Low Energy Diet Versus Conventional Diet On Adiposity, Lean Body Mass, Muscle Strength And Bone Density In Obese Adults, And Mechanisms Promoting Changes
Funder
National Health and Medical Research Council
Funding Amount
$925,990.00
Summary
Very low energy diets (VLEDs) are increasingly used to treat obesity. Of concern is the fact that VLEDs induce adaptive responses that can inhibit loss of – and promote regain of – fatness (particularly belly fat) while decreasing lean body mass, muscle strength and bone density. This project will therefore determine whether VLEDs could have negative effects on body composition that increase the risk of metabolic disease, sarcopenia or osteoporosis, and if so, what are the mechanisms involved.
Excitation-contraction Coupling In Skeletal Muscle In Health, Exercise And Disease
Funder
National Health and Medical Research Council
Funding Amount
$623,621.00
Summary
Skeletal muscle dysfunction occurs in certain diseases, aging and exercise, and can deleteriously affect lifestyle and mobility. This project investigates the molecular mechanisms involved in the complex sequence of events that occur in each individual muscle fibre, starting from stimulation by a nerve through to the fibre contracting. This should give information about causes of skeletal muscle dysfunction in myotonia, heart failure and other situations, and help development of therapies.
Muscle Fusion Defects May Be A Common Cause Of Human Dystrophies
Funder
National Health and Medical Research Council
Funding Amount
$391,419.00
Summary
While muscle fusion is a crucial step of muscle formation, it is surprising that human muscle diseases were never associated with muscle fusion defects. We have recently undertaken a genome-wide functional screen using a mouse muscle cell line. We identified 21 genes that were previously associated with muscle dystrophies in human. The aim of this project is to examine the role of those genes during muscle fusion in vivo, using the chick embryo, mouse mutants and lines from patients as models.
Cancer cachexia is a devastating disease characterised by muscle wasting, weakness and fatigue. It impairs patient quality of life and accounts for >20% of cancer-related deaths. This project will identify factors responsible for cancer cachexia and develop new strategies to alleviate wasting and weakness in cancer patients, to improve their quality of life and reduce mortality.
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.
Seeing Is Believing: Imaging Muscle Maintenance And Repair
Funder
National Health and Medical Research Council
Funding Amount
$727,191.00
Summary
We will characterise the behaviour of muscle stem cells in vivo within their micro-environment in normal and regenerating adult muscles, using high-end imaging technologies and mouse lines that we recently created. This will allow correlating cellular behaviours with the activation of signaling pathways, chosen for their likely role in the activation of satellite cells. We will then modulate the activity of these pathways in the satellite cell niche to evaluate their function.
DHPR ? Subunit Binding To A Variably Spliced Region Of RyR1: A Role In EC Coupling And Myotonic Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
We have uncovered a communication pathway between two ion channel molecules in muscle cells that underlies human movement. The pathway is critical in normal mobility and is disrupted in myotonic dystrophy. We will study the molecular components of this pathway to understand normal body function and abnormal function in mytotonic dystrophy. The work will facilitate the design of drugs to relieve the mytotonic dystrophy myopathy and form new and much needed class of specific muscle relaxants.
Manipulating Store-operated Ca2+ Entry To Improve Muscle Function In Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$516,163.00
Summary
Muscle function is regulated in a complex manner by calcium and is impaired in Duchenne muscular dystrophy (DMD). Changes in calcium regulation will be investigated in DMD patients and in an animal model using a novel approach. We will use a combination of novel experimental approaches to manipulate muscles in dystrophic mice and test for improvement in function. Results will determine the viability of a potential treatment.