Research Themes
Research Themes
Discovery
Currently unanswered questions include:
- How do muscles form their shape and complexity during embryonic development?
- What fundamental processes govern cell number?
- How many muscle fibres are formed and how many precursor cells give rise to the formation of individual muscle fibres?
- What processes determine variations in individual fibre size and functionality?
- How do muscle fibres form, grow, adapt and remodel in response to genetic perturbations, nutritional changes and activity patterns?
- What fundamental processes are altered with advancing age?
Another important and unresolved issue in skeletal muscle biology is to understand the role of the local metabolic environment in regulating muscle stem cell (MuSC) function during periods of muscle growth and development, adaptation and plasticity.
Research projects will identify how the local metabolic environment regulates MuSC identity and will reveal entirely new information about how muscles adapt to stimuli.
This research is crucial for advancing stem cell biology and harnessing the biological potential of stem cells for future applications like stem cell transplantation strategies for muscular diseases and muscle wasting conditions (thus relevant to Research Theme – Health).
Answering these questions will lead to significant biological discoveries and reinforce the Centre’s reputation for publishing fundamental research in the world’s most influential scientific journals.
Current Research Projects (Discovery)
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Therapeutic potential of skeletal muscle plasticity and slow muscle programming for muscular dystrophy
Project Leader: Prof Gordon Lynch
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Defining new roles for the Hippo signalling pathway in skeletal muscle
Project Leader: A/Prof Paul Gregorevic
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Unravelling the mysteries of E3 ubiquitin ligase in regulating skeletal muscle size and function
Project Leader: A/Prof Paul Gregorevic
Engineering and Technologies
The Centre’s expertise in muscle development, muscle injury and regeneration include the study of MuSCs, engineered muscle tissues and viral vector technologies to manipulate gene function.
These tools have potential application for cellular transplantation; creating bioartificial structures to facilitate tissue repair; and even for the formulation of nutrient dense foods.
Viral vector technologies have the capacity to selectively overexpress or downregulate genes that manipulate muscle attributes like fibre size and metabolism, and also to engineer muscle to express circulating therapeutic agents. The use of muscle organoids, including three-dimensional multicellular structures formed from muscle stem cells, fat, nerve and connective tissue components, means they have potential application for restoring muscle function after trauma or surgeries, and even for the creation of meat-like foods of variable textures and flavours.
With researchers in Science, Veterinary and Agricultural Sciences and the School of Engineering collaborating on these studies, the theme capitalises on the University’s excellence across faculties.
Current Research Projects (Engineering)
Health
The biomedical translation of the Centre’s discovery biology encompasses the study of muscle structure, function and metabolism across diseases and conditions, particularly muscle wasting pathologies such as
- ageing (sarcopenia)
- cancer cachexia
- muscular dystrophies (particularly Duchenne muscular dystrophy and facioscapulohumeral muscular dystrophy)
- inflammatory myopathies
- intensive care unit acquired wasting
The Centre’s mechanistic focus on understanding the signalling pathways regulating muscle attributes like size and metabolism, have applications for improving human performance, enhancing safety and productivity in the workplace, and for optimising sports performance through understanding the underlying bases of muscular fatigue, muscle growth, adaptation and plasticity in response to nutritional and pharmacological interventions.
Muscle wasting conditions
The biomedical translation of the Centre’s discovery biology encompasses the study of muscle structure, function and metabolism across diseases and conditions. Particularly muscle wasting pathologies including ageing (sarcopenia), cancer cachexia, muscular dystrophies (particularly Duchenne muscular dystrophy and facioscapulohumeral muscular dystrophy), inflammatory myopathies, intensive care unit acquired wasting and other muscle-related conditions.
The Centre’s mechanistic focus on understanding the signalling pathways regulating muscle attributes like size and metabolism, have applications for improving human performance, enhancing safety and productivity in the workplace, and for optimising sports performance through understanding the underlying bases of muscular fatigue, muscle growth, adaptation and plasticity in response to nutritional and pharmacological interventions.
Ageing
Australia's population is projected to be ~38 million by 2060 – a reality of record life expectancies, but one where living longer does not mean necessarily living in better health. The Productivity Commission report ‘An Ageing Australia: Preparing for the Future’ describes how ageing will affect the economy due to changes in population, participation and productivity, affecting labour supply, economic output, infrastructure and budgets.
Consider the reality of the pension age rising to 70 by 2035 and the concomitant demands on the workforce to remain healthy and productive for longer. Addressing the physical reality of this problem depends entirely on muscle and breakthroughs in understanding the biology of ageing are needed to cope sensibly and humanely with our growing older population.
Ageing is linked with a deterioration of muscle structure and function that occurs in all animals and so preserving muscle is essential for quality of life since everyday activities and even survival is dependent on a functioning musculature.
The Centre’s complementary themes of Discovery and Engineering will be applied to understanding the biological regulators of muscle ageing, especially the cellular and molecular events that dictate muscle fibre size and adaptations to the environment.
Current Research Projects (Health)
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Investigating the Dystrophin-Glycoprotein Complex to Protect Muscles from Wasting Conditions
Project Leader: Prof Gordon Lynch
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Identifying factors that improve gastrointestinal function in Duchenne's muscular dystrophy
Project Leader: Prof Gordon Lynch
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Investigating the role of cachexia in the response to surgical tumour resection in mice
Project Leader: Prof Gordon Lynch
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Defining new roles for the Hippo signalling pathway in skeletal muscle
Project Leader: A/Prof Paul Gregorevic
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Developing innovative animal and cell culture models to study and treat muscular dystrophies
Project Leader: A/Prof Paul Gregorevic
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Learning from skeletal muscles to develop new treatments for cancer
Project Leader: A/Prof Paul Gregorevic
Food
Australia’s livestock industries play a critical role in the national economy. The beef cattle, dairy, lamb, pork and poultry industries, account for 45% of the gross value of Australian agricultural output, generating returns >$22 billion.
Collaborating with affiliated researchers in the Veterinary and Agricultural Sciences, Science, and Engineering, the Centre’s discovery biology will underpin this research theme to translate new knowledge to the efficient agricultural production of meats of high nutritional value across the livestock and aquaculture (salmonid, barramundi, kingfish, abalone, oyster and shrimp) industries, and developing nutritionally-enhanced novel foods, including synthetic nutrient dense meat products.
Working with collaborators and industry partners in livestock and aquaculture, the Centre evaluates unique technologies such as nutritive steering and inducible vector-mediated phenotype manipulation, to alter muscle size and composition to improve meat quality and obviate industry problems of competitive traits from genetic selection, creating new opportunities for domestic consumption and export. Developing functional foods that address the protein needs of older adults is an urgent and unmet need.