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.
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.
Role Of UBL-5 In Mitochondrial Function And Glucose Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$647,539.00
Summary
Type 2 diabetes is caused by insulin resistance, a condition that is characterised by the inability of insulin to elicit its normal function to lower blood sugar levels. The cause of insulin resistance is not known. In this study we will determine the role of a novel gene called UBL-5 to elicit insulin resistance in muscle and fat by generating genetically-induced models in which this gene has been deleted. By understanding the role of UBL-5 in insulin resistance, better therapeutic strategies c ....Type 2 diabetes is caused by insulin resistance, a condition that is characterised by the inability of insulin to elicit its normal function to lower blood sugar levels. The cause of insulin resistance is not known. In this study we will determine the role of a novel gene called UBL-5 to elicit insulin resistance in muscle and fat by generating genetically-induced models in which this gene has been deleted. By understanding the role of UBL-5 in insulin resistance, better therapeutic strategies can be developed to treat Type 2 diabetes.Read moreRead less
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.
Influence Of In Utero Environment On Diaphragm Structure And Function
Funder
National Health and Medical Research Council
Funding Amount
$494,966.00
Summary
The diaphragm is the major muscle involved in breathing. Normal function of the diaphragm is essential to survival. Preterm babies may be exposed to infection and other agents that interfere with diaphragm development and make breathing efforts weaker after birth, potentially leading to respiratory failure. This study will study diaphragms of preterm lambs to determine how fetal exposure to infection and steroids affect fetal diaphragm development, and if adverse effects are prevented by fetal t ....The diaphragm is the major muscle involved in breathing. Normal function of the diaphragm is essential to survival. Preterm babies may be exposed to infection and other agents that interfere with diaphragm development and make breathing efforts weaker after birth, potentially leading to respiratory failure. This study will study diaphragms of preterm lambs to determine how fetal exposure to infection and steroids affect fetal diaphragm development, and if adverse effects are prevented by fetal treatment with blocking agents.Read moreRead less