Muscle Bioengineering

The Muscle Bioengineering group focuses on different muscle diseases, including genetic muscle conditions that affect children such as Facioscapulohumeral muscular dystrophy (FSHD).

To study these diseases, the group uses stem cells to generate human skeletal muscle tissue in the lab.

These ‘mini muscles’ act and function like the muscle in your body, giving the Muscle Bioengineering group the unique ability to measure important properties like muscle strength, kinetics and endurance. .

Using this approach, they can generate thousands of mini muscles in the lab to better understand the biology of muscle disease and screen for potential new therapies.

Watch the video of bioengineered skeletal muscle contracting and producing force in a dish.

Contact us

For more information on our research, please contact us.

Associate Professor Richard Mills
Group Leader / Principal Research Fellow
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Our projects

Facioscapulohumeral muscular dystrophy therapeutic target discovery 

Facioscapulohumeral muscular dystrophy (FSHD) is a common genetic muscle disorder that causes progressive weakness and wasting of muscles in the face, shoulder blades, and upper arms. It is caused by mis-expression of the double homeobox protein 4 gene (DUX4). Within the lab, we can model FSHD through inducing DUX4 expression or using patient cells to make muscle fibres and bioengineered skeletal muscle.

Using these approaches, we performed a 30,000-compound screen to identify molecules that are protective in FSHD. Of these we identified 6 compounds that were protective across all healthy and patient muscle.

This project will continue to develop these drugs in the aim of developing a treatment for FSHD.

Advanced maturation of bioengineered skeletal muscle 

In general, stem-cell derived systems are more representative of neonatal tissue rather than adult, which can limit their ability for disease modelling and drug discovery.

Lab-made skeletal muscle does not recapitulate adult function (10x fold weaker) or adult metabolism, which makes modelling diseases like type 2 diabetes impossible.

We aim to develop approaches to accelerate bioengineered muscle maturation to adult-like tissue and demonstrate their utility. 

Modelling skeletal muscle aging (sarcopenia) 

Sarcopenia is the progressive, age -related loss of skeletal muscle mass, strength and function. These age-related changes can be accelerated by environmental factors such as sedentary lifestyle or prolonged bed rest (immobilisation).

This project investigates how bioengineered muscle generated from older individuals differs from younger individuals and their response to ‘bed-rest’. Our approach shows that muscle generated from older donor muscle stem cells (approximately 70 years old) have decreased strength compared to younger donors (approximately 30 years old), and that mechanical unloading of tissue mimics skeletal muscle disuse.

Using this approach, we are investigating the interplay between ageing and bed-rest, to uncover novel mechanistic insights and therapeutic targets for age-related muscle weakness.

Funding

• National Health and Medical Research Council (NHMRC)
• reNEW Center for Stem Cell Medicine
• Medical Research Future Fund (MRFF)
• Wellcome LEAP- Dynamic Resilience Program
• Jain Foundation

Collaborations

• Professor Andy Philp (Centenary Institute)
• Dr Peter Houweling
• Dr Sean Humphrey
• Professor James Hudson (QIMR Berghofer)
• Professor Enzo Porrello
• Professor David Elliot
• Dr Jessica Vanslambrouck
• Dr Rhiannon Werder
• Dr Holly Voges
• A/Professor Ben Parker (University of Melbourne)
• Dr Kevin Watt
• Professor Matthew Watt (University of Melbourne)
• Professor Paul Gregorevic (University of Melbourne)
• Professor Niels Geijsen (Leiden University)
• Professor Mirana Ramialison
• A/Professor Fernando Rossello

Featured publications

Pocock MW, et.al., Mills RJ*, Hudson JE*. Maturation of human cardiac organoids enables complex disease modelling and drug discovery. Nature Cardiovascular Research (2025) 4(7):821-840. 

Mills, R.J., et al., BET Inhibition Blocks Inflammation-Induced Cardiac Dysfunction and SARS-CoV-2 Infection. Cell (2021) 184(8). 

Mills, R.J., et al.,  Drug screening in human PSC-cardiac organoids identifies pro-proliferative compounds acting via the mevalonate pathway. Cell Stem Cell (2019) 24(6):895-907.e6. 

Mills, R.J., et al.,  Development of a human skeletal micro muscle platform with pacing capabilities. Biomaterials (2019) 198:217-227. 

Mills, R.J., et al.,  Neurturin is a PGC-1α1-controlled myokine that promotes motor neuron recruitment and neuromuscular junction formation. Molecular Metabolism (2018) 7:12-22. 

Mills, R.J., et al.,  Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest. PNAS (2017) 114(40): 8372-81.