Muscle Research Group Leader and Institute Director, Professor Kathryn North was the first to identify the common genetic variation in alpha-actinin-3 (R577X) that influences muscle function and performance in elite athletes and the general population (the ‘gene for speed').
One in five Australians and more than one billion humans worldwide do not express ACTN3 in their skeletal muscle. The absence of ACTN3 alters skeletal muscle performance, metabolism, mass, our response to exercise and susceptibility to muscle damage. Our research into the ACTN3 gene have greatly improved understanding of normal skeletal muscle biology, as well as highlighting major roles for health and fitness across the human lifespan.
The use of recombinant adeno associated viral (rAAV) vectors to assess mechanisms of muscle mass and function in wild-type and Actn3 KO mice
The absence of a-actinin-3 significantly reduces muscle mass in humans and mice (Actn3 KO). Researchers will use rAAV as a tool to over-express various proteins involved in the muscle hypertrophy/atrophy pathway to assess the role of ACTN3 in skeletal muscle mass and development.
Defining the role of α-actinin-3 in brown adipose tissue and the influence of ACTN3 genotype in adaptive response to diet and cold exposure
The ACTN3 X-allele has shown strong, positive selection during recent human evolution. The mechanism for this change is currently unknown. ACTN3 has recently been identified in BAT, a key organ responsible for heat generation in both animals and humans. This project will explore the role and function of ACTN3 in both skeletal muscle and BAT in response to caloric restriction and exposure to cold.
Characterising ACTN3 genotype as a modifier of Duchenne muscular dystrophy (DMD) and skeletal muscle regeneration
DMD is the most commonly inherited skeletal muscle disorder that affects boys. It results in devastating muscle wasting and premature death. Using our novel mouse model the team will assess the role that ACTN3 plays in the progression of DMD and its effects on muscle regeneration. Identifying the role of ACTN3 in disease will guide the selection of effective interventions to improve muscle metabolism, and maintain skeletal strength during the progression of DMD and other inherited muscle diseases.
Investigating the genetic influence on athletic performance (POWERGENE consortium)
Researchers have established a multinational consortium to study the genetic influence of sprint/power performance in elite athletes. Understanding the genes which play a role in the elite athlete will highlight novel pathways that influence skeletal muscle function, metabolism and performance. With this understanding researchers will potentially identify novel therapeutic pathways for both inherited and acquired diseases; seeking to improve muscle metabolism, bulk and strength.
- Dr Stewart Head – The University of New South Wales
- Associate Professor Nigel Clarke – Institute for Neuroscience and Muscle Research, University of Sydney
- Dr Kate G.R Quinlan – University of New South Wales
- Dr Paul Gregorevic – Baker IDI Heart and Diabetes Institute
- Dr Aaron Shindeler – University of Sydney
- Professor David Bishop – ISEAL, Victoria University
- Dr Nir Eynon – ISEAL, Victoria University
- ACTN3 genotype influences skeletal muscle mass regulation and response to dexamethasone. 2021
- A transformative translational change programme to introduce genomics into healthcare: a complexity and implementation science study protocol. 2019
- Association Between Hematological Parameters and Iron Metabolism Response After Marathon Race and ACTN3 Genotype. 2019
- Australian Genomics: A Federated Model for Integrating Genomics into Healthcare. 2019
- Building a learning community of Australian clinical genomics: a social network study of the Australian Genomic Health Alliance. 2019
- Cullin-3 dependent deregulation of ACTN1 represents a new pathogenic mechanism in nemaline myopathy. 2019
- Integrating Genomics into Healthcare: A Global Responsibility. 2019
- Statistical Considerations for Exercise Protocols Aimed at Measuring Trainability. 2019
- Attention to faces in social context in children with neurofibromatosis type 1. 2018
- Branched fibers from old fast-twitch dystrophic muscles are the sites of terminal damage in muscular dystrophy. 2018
- CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63. 2018
- Effects of methylphenidate on cognition and behaviour in children with neurofibromatosis type 1: a study protocol for a randomised placebo-controlled crossover trial. 2018
- More than a 'speed gene': ACTN3 R577X genotype, trainability, muscle damage, and the risk for injuries. 2018
- Nemaline myopathy and distal arthrogryposis associated with an autosomal recessive TNNT3 splice variant. 2018
- No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running times in 698 Caucasian athletes. 2018
- Preliteracy impairments in children with neurofibromatosis type 1. 2018
- Social Function and Autism Spectrum Disorder in Children and Adults with Neurofibromatosis Type 1: a Systematic Review and Meta-Analysis. 2018
- The Effect of ACTN3 Gene Doping on Skeletal Muscle Performance. 2018
- Agreement between concern about autism spectrum disorder at the time of referral and diagnosis, and factors associated with agreement. 2017
- Androgen Action via the Androgen Receptor in Neurons Within the Brain Positively Regulates Muscle Mass in Male Mice. 2017
- Atypical Local Interference Affects Global Processing in Children with Neurofibromatosis Type 1. 2017
- Co-option of the cardiac transcription factor Nkx2.5 during development of the emu wing. 2017
- Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases. 2017
- Evidence for ACTN3 as a genetic modifier of Duchenne muscular dystrophy. 2017
- Exploring the relationship between α-actinin-3 deficiency and obesity in mice and humans. 2017
- Facial emotion recognition, face scan paths, and face perception in children with neurofibromatosis type 1. 2017
- Impaired engagement of the ventral attention system in neurofibromatosis type 1. 2017
- Improving genetic diagnosis in Mendelian disease with transcriptome sequencing. 2017
- Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness. 2017
- Neurofibromatosis Type 2. 2017
- Preface: genomics and biology of exercise is undergoing a paradigm shift. 2017
- The influence of α-actinin-3 deficiency on bone remodelling markers in young men. 2017
- The neural basis of deficient response inhibition in children with neurofibromatosis type 1: Evidence from a functional MRI study. 2017
- ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: a multi-cohort study. 2016
- Analysis of the ACTN3 heterozygous genotype suggests that a-actinin-3 controls sarcomeric composition and muscle function in a dose-dependent fashion. 2016
- Can in-the-moment diary methods measure health-related quality of life in Duchenne muscular dystrophy? 2016
- How does α-actinin-3 deficiency alter muscle function? Mechanistic insights into ACTN3, the 'gene for speed'. 2016
- Limb patterning genes and heterochronic development of the emu wing bud. 2016
- Mutations in HSPB8 causing a new phenotype of distal myopathy and motor neuropathy. 2016
- Neurocognitive outcomes in neurofibromatosis clinical trials: Recommendations for the domain of attention. 2016
- No Evidence of a Common DNA Variant Profile Specific to World Class Endurance Athletes. 2016
- Phonics Training Improves Reading in Children with Neurofibromatosis Type 1: A Prospective Intervention Trial. 2016
- Physical activity and the use of standard and complementary therapies in Duchenne and Becker muscular dystrophies. 2016
- Progress and prospects of gene therapy clinical trials for the muscular dystrophies. 2016
- Prominent scapulae mimicking an inherited myopathy expands the phenotype of CHD7-related disease. 2016
- Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1. 2016
- Rodent models for resolving extremes of exercise and health. 2016
- The Future of Genomic Research in Athletic Performance and Adaptation to Training. 2016
- TOR1AIP1 as a cause of cardiac failure and recessive limb-girdle muscular dystrophy. 2016
- Uptake of health monitoring and disease self-management in Australian adults with neurofibromatosis type 1: strategies to improve care. 2016
- Variants in SLC18A3, vesicular acetylcholine transporter, cause congenital myasthenic syndrome. 2016
- Variants in the Oxidoreductase PYROXD1 Cause Early-Onset Myopathy with Internalized Nuclei and Myofibrillar Disorganization. 2016
- All the World's a Stage: Facilitating Discovery Science and Improved Cancer Care through the Global Alliance for Genomics and Health. 2015
- Altered Ca2+ kinetics associated with a-actinin-3 deficiency may explain positive selection for ACTN3 null allele in human evolution. 2015
- Developmental trajectories of young children with neurofibromatosis type 1: a longitudinal study from 21 to 40 months of age. 2015
- Direct-to-consumer genetic testing for predicting sports performance and talent identification: Consensus statement. 2015
- Elite athletes' genetic predisposition for altered risk of complex metabolic traits. 2015
- Evidence-based guideline summary: evaluation, diagnosis, and management of congenital muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Issues Review Panel of the American Association of Neuromuscular & Electrodiagnostic Medicine. 2015
- Exercise training and DNA methylation in humans. 2015
- Expanding the phenotype of GMPPB mutations. 2015
- Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene. 2015
- MCT1 A1470T: a novel polymorphism for sprint performance? 2015
- Muscle weakness in children with neurofibromatosis type 1. 2015
- Muscle weakness in TPM3-myopathy is due to reduced Ca2+-sensitivity and impaired acto-myosin cross-bridge cycling in slow fibres. 2015
- Mutations in PIGY: expanding the phenotype of inherited glycosylphosphatidylinositol deficiencies. 2015
- Neuronal control of bone and muscle. 2015
- PGC-related gene variants and elite endurance athletic status in a Chinese cohort: a functional study. 2015
- Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2. 2015
- Recent studies of ovine neuronal ceroid lipofuscinoses from BARN, the Batten Animal Research Network. 2015
- Skeletal muscle and motor deficits in Neurofibromatosis Type 1. 2015
- The Athlome Project Consortium: A Concerted Effort to Discover Genomic and other "OMIC" Markers of Athletic Performance. 2015
- The Impact of Neurofibromatosis Type 1 on the Health and Wellbeing of Australian Adults. 2015
- Vitamin D Receptor Ablation and Vitamin D Deficiency Result in Reduced Grip Strength, Altered Muscle Fibers, and Increased Myostatin in Mice. 2015
- a-Actinin-3 deficiency alters muscle adaptation in response to denervation and immobilization. 2014
- Approach to the diagnosis of congenital myopathies. 2014
- Calpain cleavage within dysferlin exon 40a releases a synaptotagmin-like module for membrane repair. 2014
- Diagnostic approach to the congenital muscular dystrophies. 2014
- EPAS1 gene variants are associated with sprint/power athletic performance in two cohorts of European athletes. 2014
- Longitudinal assessment of cognition and T2-hyperintensities in NF1: an 18-year study. 2014
- Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies. 2014
- Over-expression of DMRT1 induces the male pathway in embryonic chicken gonads. 2014
- Properties of regenerated mouse extensor digitorum longus muscle following notexin injury. 2014
- Relationship between cognitive dysfunction, gait, and motor impairment in children and adolescents with neurofibromatosis type 1. 2014
- The genetic and neuroanatomical basis of social dysfunction: lessons from neurofibromatosis type 1. 2014
- The vitamin D receptor (VDR) is expressed in skeletal muscle of male mice and modulates 25-hydroxyvitamin D (25OHD) uptake in myofibers. 2014
- ACTN3 genotype influences muscle performance through the regulation of calcineurin signaling 2013
- Cognitive Features that Distinguish Preschool-Age Children with Neurofibromatosis Type 1 from Their Peers: A Matched Case-Control Study 2013
- Genes for Elite Power and Sprint Performance: ACTN3 Leads the Way 2013
- Mutations in BICD2 Cause Dominant Congenital Spinal Muscular Atrophy and Hereditary Spastic Paraplegia 2013
- Mutations in GDP-Mannose Pyrophosphorylase B Cause Congenital and Limb-Girdle Muscular Dystrophies Associated with Hypoglycosylation of alpha-Dystroglycan 2013
- Mutations in KLHL40 Are a Frequent Cause of Severe Autosomal-Recessive Nemaline Myopathy 2013
- Social functioning in adults with neurofibromatosis type 1 2013
- Reactivity of the sulfhydryl groups of soluble succinate dehydrogenase. 1976