Faculty of Health and Medical Sciences

Muscle Research Group

 

Prof. Miranda D Grounds

Laboratory:
Muscle Research Group
Location:
School of Anatomy, Physiology and Human Biology, the University of Western Australia
Websites:

https://school.anhb.uwa.edu.au/personalpages/grounds/


Area of Expertise

For over 40 years our research into skeletal muscle has used in vivo mouse (and other animal) models to investigate a wide range of cellular and molecular factors controlling the post-natal growth, maintenance, hypertrophy/atrophy, damage and regeneration of normal, diseased and ageing skeletal muscles, plus tissue engineering.  The regenerative interests include topics of stem cells, inflammation, myogenesis, fibrosis and the central role of the extracellular matrix. We then apply this broad knowledge of skeletal muscle biology to provide deep insight into the molecular basis of muscular dystrophies and the age-related loss of skeletal muscle mass and function known as sarcopenia, with the aim of developing targeted therapies.  The ageing research is broad and has resulted in a focus on neuromuscular changes involving the sciatic nerves and spinal cord, plus systemic benefits of exercise.We have long-standing research experience with the mdx mouse model for the lethal childhood disease Duchenne Muscular Dystrophy (DMD) and optimising pre-clinical experiments and trials. This research includes pioneering myogenic cell therapies, novel use of drugs that target the proinflammatory cytokine TNF to block inflammation and, more recently, drugs that reduce protein thiol oxidation to protect dystrophic muscles from necrosis; leading to a current focus on taurine with a proposed clinical trial for DMD boys. This research has a strong translational emphasis: Miranda is involved with international muscle networks including TreatNMD, to help develop Standard Operating Procedures for pre-clinical mouse models, and she is a core member of the TreatNMD clinical trial evaluation committee (TACT). A major current interest is investigating the molecular basis for the high levels of lipid, and later adipocyte replacement of myofibres, in the dysferlin deficient limb girdle muscle dystrophy that affects adults. This research is widely recognised internationally with >200 publications. Miranda also co-founded SymbioticA, the leading biological studio/laboratory for Art & Science.


Top 5 Recent Publications

  1. Grounds MD, Radley-Crabb HG, Terrill J, Robertson T, Papadimitriou J, Spuler S, Shavlakadze T. (2014) Lipid accumulation in dysferlin-deficient muscles.  American Journal of Pathology. 184(6):1668-1676 PMID:  24685690
  2. Barns M, Gondro C, Tellam R, Radley-Crabb HG, Grounds MD, Shavlakadze T. (2014) Molecular analyses provide insight into mechanisms underlying sarcopenia and myofibre denervation in old skeletal muscles of mice.  International Journal of Biochemistry and Cell Biology. 53:174-85 PMID: 24836906
  3. Krishnan VS, White Z, McMahon CD Hodgetts SI, Fitzgerald L, Shavlakadze T, Harvey AR, Grounds MD. (2016) A neurogenic perspective of sarcopenia: time course study of sciatic nerves from aging mice. Journal of Neuropathology and Experimental Neurology 75(5):464-78. PMID:27030741.
  4. Butchart L, Shavlakadze T, Fox A, Grounds MD. (2016) The long and short of non-coding RNAs during post-natal growth and differentiation of skeletal muscles: focus on lncRNA and miRNAs. Differentiation 92(5):237-248.  PMID:  27292314
  5. Terrill JR, Duong N, Turner R, Le Guiner C, Boyzatis A, Kettle AJ, Grounds MD, Arthur PG. (2016) Levels of inflammation and oxidative stress, and a role for taurine in dystropathology of the Golden Retriever Muscular Dystrophy dog model for Duchenne Muscular Dystrophy.  Redox Biology 9: 276-286. PMID: 27611888


Publications with CCTRM byline

  1. White Z, White RB, McMahon C, Grounds MD,  Shavlakadze T. (2016) High mTORC1 signaling is maintained and protein degradation pathways disturbed in old murine skeletal muscles in the fasted state. International Journal of Biochemistry and Cell Biology. Jun 22;78:10-21 PMID: 27343428
  2. White Z, Terrill J, White RB, McMahon C, Sheard P, Grounds MD, Shavlakadze T. (2016) Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL/6J mice.  Skeletal Muscle Dec 13;6(1):45.  PMID: 27964759


Recent Grant Successes

  1. 2017 Duchenne Parent Project Netherlands
  2. 2017 Neurotrauma Research Program
  3. 2017- 2018 Muscular Dystrophy Association (MDA) USA
  4. 2016-2018 Australian Research Council (ARC)
  5. 2014-2016 National Health & Medical Research Council (NHMRC) Australia
  6. 2014 Muscular Dystrophy Association, USA
  7. 2013 Jain Foundation (USA)
  8. 2013 Duchenne Parent Project, Netherlands
  9. 2012-2015 ARC Linkage Round 1

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