Anatomy, Physiology and Human Biology

Skeletal Muscle Physiology

Further Information

Contact a supervisor for detailed information on student research projects

  Assistant Professor Gavin Pinniger
Assoc/Prof Gavin Pinniger

 Assoc/Prof Anthony Bakker
Dr Tony Bakker

 Professor Miranda Grounds
E/Prof. Miranda Grounds

 Dr Peter Noble
Dr Peter Noble

 Professor Jane Pillow
Prof Jane Pillow

 Assoc/Prof Peter Arthur
Dr Peter Arthur (Biochemistry)

Skeletal muscles serve numerous functions that are essential for life. Not only do they provide the power required for movement and locomotion, but they also have vital roles in respiration, thermoregulation and metabolism. Not surprisingly, the loss of muscle mass and/or muscle function can be life threatening. Skeletal muscles of pre-term babies, elderly people and of people suffering from muscle diseases such as the debilitating Duchenne muscular dystrophy (DMD) are highly vulnerable to injury and are inherently weaker than healthy muscle. The goal of our research group is to understand the mechanisms of muscle damage and contractile dysfunction associated with ageing and disease and to evaluate potential therapeutic treatments to alleviate the severity of symptoms and improve the quality of life of these individuals.

Using a range of experimental models from in vitro single cell recordings to in vivo experiments on whole animals we investigate the molecular processes regulating muscle contraction and the mechanisms of contractile dysfunction from a cellular and systems approach. Students will be exposed to experimental techniques including recovery anaesthesia and surgery, microdissection of whole muscle and single muscle fibres, cell-culture and calcium imaging. We have several multi-disciplinary collaborations with local and international researches and are particularly interested in:

i) Factors that affect diaphragm function and contribute to breathing problems in pre-term infants;

ii) Unravelling the molecular processes of force enhancement in skeletal muscle;

iii) Evaluating therapeutic treatments for Duchenne muscular dystrophy

Specific details of Skeletal Muscle Physiology projects are listed below. Although the majority of this work is based on widely accepted and well established animal models of muscle disorders, there is also the possibility of projects working on skeletal muscle function in humans as well .

Factors that affect diaphragm function and contribute to breathing problems in pre-term infants.

With Prof Jane Pillow, Dr Tony Bakker,  Dr Peter Noble

Project Outline

A functional diaphragm is critically important to successful establishment of unsupported spontaneous breathing. The incidence of respiratory failure is higher in preterm babies than at any other time of life and the functional immaturity of the preterm diaphragm is likely to contribute to this respiratory failure. The preterm baby needs to generate sufficient inspiratory force to overcome the mechanical disadvantages imposed by a highly compliant chest wall, low levels of endogenous surfactant and noncompliant, structurally immature lungs. Therefore, the integrity of the diaphragm at delivery may critically influence the resilience of the infant to developing respiratory failure after birth. Optimising in utero diaphragm development and the structure and function of the diaphragm at birth is essential to ensure a healthy start to life for these extremely vulnerable babies. We aim to determine the effect of common, clinically relevant antenatal exposures (inflammation, glucocorticoids) and the timing of these insults on the metabolic, functional and structural phenotype of the fetal and newborn diaphragm.

Project is suitable for

Honours, Masters and PhD

Supervisor

Associate Professor Gavin Pinniger

 
Essential qualifications

For Honours: An appropriate undergraduate degree with a minimum weighted average of 65% in the level 3 subjects that comprise the relevant major, from an approved institution. Applicants will be assessed on a case-by-case basis.

For Masters or PhD : An appropriate Honours degree or equivalent research experience from an approved institution. Applicants will be assessed on a case-by-case basis.

Back to top

Unravelling the molecular processes of force enhancement in skeletal muscle.

With Dr Tony Bakker


Project Outline

Muscle contraction involves the cyclic interaction between myosin heads (crossbridges) on the thick filaments with binding sites on the thin (actin) filaments, a process that is driven by ATP hydrolysis. The original Huxley (1957) model for crossbridge cycling provides the foundation for current theories of muscle contraction and can account for various aspects of skeletal muscle function such as the force-length relationship and the force-velocity relationship during muscle shortening (concentric contraction). However, current models of muscle contraction fail to fully account for the force response when an active muscle is lengthening (eccentric contraction), or for the force enhancement observed with high frequency doublet stimulations.

Experiments on isolated muscle preparations have shown that stretch of an active muscle causes a transient increase in force arising from the strain of both contractile (crossbridges) and non-contractile (structural) components of the sarcomere. The relative contributions of these components can be determined from their force-velocity characteristics and by the use of specific myosin inhibitors (Pinniger et al., J Physiol, 2006). Structural proteins such as titin, act to stabilize the sarcomere allowing the transmission of force within and between muscle fibres and disruption to these proteins is associated with the development of exercise-induced muscle damage. Although the contribution of the structural proteins (titin) to stretch-induced force enhancement is unknown, there is evidence that titin stiffness increases upon activation in a calcium-dependent manner. This calcium dependent increase in stiffness may also account for some of the force potentiation observed with doublet stimulation.

This study aims to determine the contribution of titin filaments to calcium dependent increases in muscle stiffness. Experiments will be performed on single muscle fibres and to determine the calcium sensitivity of stretch-induced force enhancement and doublet induced force potentiation. This research is focused on unravelling the complex molecular mechanisms of tension development during muscle activation. The outcomes of this research will provide valuable insight into the mechanisms of exercise induced muscle damage and help to identify key features of the adaptation process brought about by repeated exposure to eccentric exercise.

Project is suitable for

Honours, Masters and PhD

Supervisor

Associate Professor Gavin Pinniger

Essential qualifications

For Honours: An appropriate undergraduate degree with a minimum weighted average of 65% in the level 3 subjects that comprise the relevant major, from an approved institution. Applicants will be assessed on a case-by-case basis.

For Masters or PhD : An appropriate Honours degree or equivalent research experience from an approved institution. Applicants will be assessed on a case-by-case basis.

Back to top

 

The role of inflammation and reactive oxygen species in skeletal muscle weakness in Duchenne Muscular Dystrophy (DMD)

With Dr Peter Arthur (Biochemistry) and Prof. Miranda Grounds

Project Outline

Due to the absence of functional dystrophin protein, the skeletal muscles of DMD patients are inherently weaker and highly susceptible to muscle damage. Localized muscle damage and membrane lesions allow the infiltration of extracellular calcium and key inflammatory cytokines such as tumor necrosis factor (TNF) which stimulate the increased production of reactive oxygen species (ROS). The accumulation of these reactive molecules can lead to degradation of cellular constituents that can lead to cell death (myofibre necrosis). Excessive ROS production can also contribute to muscle weakness by reversible modification of protein function. We have shown that blockade of TNF activity (using cV1q, a mouse specific TNF antibody) results in a striking reduction of myofibre necrosis and muscle weakness in dystrophic mdx mice. We have also shown that anti-oxidant compounds such as N-acetyl cysteine (NAC) also reduce the severity of muscle damage and weakness in dystrophic muscle. However, our recent studies suggest that NAC may act indirectly by increasing the availability of cysteine derivatives such as taurine. This project will investigate the hypothesis that the inherent weakness in dystrophic muscle is caused by the lack of taurine availability and that taurine supplementation is a potential therapeutic treatment for DMD. Experiments will be carried out on normal healthy mice and dystrophic, mdx mice using a combination of in vivo eccentric muscle testing as well as isolated, intact muscle fibre experiments.

Project is suitable for

Honours, Masters and PhD

Supervisor

Associate Professor Gavin Pinniger

 
Essential qualifications

For Honours: An appropriate undergraduate degree with a minimum weighted average of 65% in the level 3 subjects that comprise the relevant major, from an approved institution. Applicants will be assessed on a case-by-case basis.

For Masters or PhD : An appropriate Honours degree or equivalent research experience from an approved institution. Applicants will be assessed on a case-by-case basis.

Back to top