研究领域

Animal Physiology - Cell

Over the last 22 years Dr Head’s research has been in the general area of skeletal muscle physiology. In particular his interest has been in the area of the muscular dystrophies and studying the role of [Ca2+]i in the physiology and pathophysiology of skeletal muscle. Dr Head’s laboratory has also performed substantial work on dystrophic mdx mouse cerebellum dysfunction. Dystrophin, the protein missing in Duchenne Muscular Dystrophy, is also normally expressed in the brain. His group demonstrated that dystrophin functions to cluster GABAA receptors at the post synaptic density of Purkinje neurons and in its absence that amplitude of inhibitory GABA currents is reduced by 50%, additionally; there is a 50% blunting of the Long Term Depression response at the parallel fibre/Purkinje synapse. THE GENE FOR SPEED:- Dr Head has been involved in research into the role of skeletal muscle Z line cytoskeletal protein alpha-actinin-3 since. The gene encoding this protein is colloquially termed the “gene for speed”. The understanding of the consequences for skeletal muscle function of an absence of α-actinin-3, both in athletes and the general population, is of global importance given the mutation is present in more than 1 billion people worldwide. To date Dr Head has analysed the basic contractile properties of α-actinin-3 deficient muscle demonstrating that in some aspects the mutant fast-twitch muscle behaves like a slow-twitch muscle, relaxing and fatiguing more slowly than its wild-type counterpart and also that the mutation renders fast-twitch muscle fibres cold acclimatised and pre-endurances trained; which may explain the positive selection pressures on the mutation over the last 100,000 years of human evolution. SUMMARY OF RESEARCH ACHIEVEMENTS:- Between 1990 and 1993 Dr Head was among the first researchers to investigate the [Ca2+ ]i handling and electrophysiological properties of two muscular dystrophies which lacked the cytoskeleton proteins laminin α-2 and dystrophin, respectively. These papers are still cited in current reviews on contractile properties and [Ca2+]i handling in muscular dystrophies. More recently Dr Heads has continued his research into contractile and calcium deficiencies which result when cytoskeletal proteins are absent from excitable cells Dr Head’s research group has been invited to talk and participate at international conferences in Paris (France) and Philadelphia (USA) to present on the role played by the cytoskeletal protein “dystrophin” in [Ca2+]i handling of neural tissues and contractile properties of skeletal muscle. As a further recognition of Dr Head’s international standing in this research area of cellular [Ca2+]i regulation and contractile properties of muscle cells, he was appointed to a Visiting Professorship at the University of Liverpool UK (During 2006) . Dr Head has supervised 8 PhD students.

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Hogarth MW; Garton FC; Houweling PJ; Tukiainen T; Lek M; Macarthur DG; Seto JT; Quinlan KGR; Yang N; Head SI; North KN, 2016, 'Analysis of the ACTN3 heterozygous genotype suggests that α-actinin-3 controls sarcomeric composition and muscle function in a dose-dependent fashion', Human Molecular Genetics, vol. 25, no. 5, pp. 866 - 877, http://dx.doi.org/10.1093/hmg/ddv613 Cooper ST; Head SI, 2015, 'Membrane Injury and Repair in the Muscular Dystrophies', The Neuroscientist: reviews at the interface of basic and clinical neurosciences, vol. 21, no. 6, pp. 653 - 668, http://dx.doi.org/10.1177/1073858414558336 Head SI; Chan S; Houweling PJ; Quinlan KGR; Murphy R; Wagner S; Friedrich O; North KN, 2015, 'Altered Ca2+ Kinetics Associated with α-Actinin-3 Deficiency May Explain Positive Selection for ACTN3 Null Allele in Human Evolution', PLoS Genetics, vol. 11, no. 1, http://dx.doi.org/10.1371/journal.pgen.1004862 Yu ZY; Tan JC; McMahon AC; Iismaa SE; Xiao H; Kesteven SH; Reichelt ME; Mohl MC; Smith NJ; Fatkin D; Allen D; Head SI; Graham RM; Feneley MP, 2014, 'RhoA/ROCK signaling and pleiotropic α1A-adrenergic receptor regulation of cardiac contractility', PLoS One, vol. 9, no. 6, http://dx.doi.org/10.1371/journal.pone.0099024 Head SI; Chan S; Chen G; Hardeman EC; Houweling PJ, 2014, 'Properties of regenerated mouse extensor digitorum longus muscle following notexin injury', Experimental Physiology, http://dx.doi.org/10.1113/expphysiol.2013.077289 Head SI; Arber MB, 2013, 'An active learning mammalian skeletal muscle lab demonstrating contractile and kinetic properties of fast- and slow-twitch muscle', Advances in Physiology Education, vol. 37, no. 4, pp. 405 - 414, http://dx.doi.org/10.1152/advan.00155.2012 Head S, 2012, 'Does skeletal muscle fiber branching play a role in the inability of old EDL dystrophic muscle to resist large passive stretches?', Journal of Applied Physiology, vol. 112, no. 2, pp. 331, http://dx.doi.org/10.1152/japplphysiol.01355.2011 Head SI; Ha TN, 2011, 'Acute inhibitory effects of clenbuterol on force, Ca 2+ transients and action potentials in rat soleus may not involve the β 2-adrenoceptor pathway', Clinical and Experimental Pharmacology and Physiology, vol. 38, no. 9, pp. 638 - 646, http://dx.doi.org/10.1111/j.1440-1681.2011.05574.x Head SI, 2011, 'Old men still have the skeletal muscle contractile function to get up and go even after they have had their leg in a cast', The Journal of Physiology, vol. 589, no. 19, pp. 4639, http://dx.doi.org/10.1113/jphysiol.2011.218826 Seto JT; Lek M; Quinlan KGR; Houweling PJ; Zheng XF; Garton F; MacArthur DG; Raftery JM; Garvey SM; Hauser MA; Yang N; Head SI; North KN, 2011, 'Deficiency of α-actinin-3 is associated with increased susceptibility to contraction-induced damage and skeletal muscle remodeling', Human Molecular Genetics, vol. 20, no. 15, pp. 2914 - 2927, http://dx.doi.org/10.1093/hmg/ddr196 Nikolova-Krstevski V; Leimena C; Xiao XH; Kesteven S; Tan JC; Yeo LS; Yu ZY; Zhang Q; Carlton A; Head S; Shanahan C; Feneley MP; Fatkin D, 2011, 'Nesprin-1 and actin contribute to nuclear and cytoskeletal defects in lamin A/C-deficient cardiomyopathy', Journal of Molecular and Cellular Cardiology, vol. 50, no. 3, pp. 479 - 486, http://dx.doi.org/10.1016/j.yjmcc.2010.12.001 Kueh SLL; Dempster J; Head SI; Morley JW, 2011, 'Reduced postsynaptic GABAA receptor number and enhanced gaboxadol induced change in holding currents in Purkinje cells of the dystrophin-deficient mdx mouse', Neurobiology of Disease, vol. 43, no. 3, pp. 558 - 564, http://dx.doi.org/10.1016/j.nbd.2011.05.002 Chan S; Seto JT; Houweling PJ; Yang N; North KN; Head SI, 2011, 'Properties of extensor digitorum longus muscle and skinned fibers from adult and aged male and female ACTN3 knockout mice', Muscle and Nerve, vol. 43, no. 1, pp. 37 - 48, http://dx.doi.org/10.1002/mus.21778 Chan S; Head SI, 2011, 'The role of branched fibres in the pathogenesis of Duchenne muscular dystrophy', Experimental Physiology, vol. 96, no. 6, pp. 564 - 571, http://dx.doi.org/10.1113/expphysiol.2010.056713 Head SI; Greenaway B; Chan S, 2011, 'Incubating isolated mouse EDL muscles with creatine improves force production and twitch kinetics in fatigue due to reduction in ionic strength', PLoS One, vol. 6, no. 8, http://dx.doi.org/10.1371/journal.pone.0022742 Head SI, 2010, 'Branched fibres in old dystrophic mdx muscle are associated with mechanical weakening of the sarcolemma, abnormal Ca2+ transients and a breakdown of Ca2+ homeostasis during fatigue', Experimental Physiology, vol. 95, no. 5, pp. 641 - 656, http://dx.doi.org/10.1113/expphysiol.2009.052019 Anderson JL; Morley JW; Head SI, 2010, 'Enhanced homosynaptic LTD in cerebellar Purkinje cells of the dystrophic mdx mouse', Muscle and Nerve, vol. 41, no. 3, pp. 329 - 334, http://dx.doi.org/10.1002/mus.21467 Chan S; Head SI, 2010, 'Age- and gender-related changes in contractile properties of non-atrophied EDL muscle', PLoS One, vol. 5, no. 8, http://dx.doi.org/10.1371/journal.pone.0012345 Kueh SLL; Head SI; Morley JW, 2008, 'GABAA receptor expression and inhibitory post-synaptic currents in cerebellar Purkinje cells in dystrophin-deficient mdx mice', Clinical and Experimental Pharmacology and Physiology, vol. 35, no. 2, pp. 207 - 210, http://dx.doi.org/10.1111/j.1440-1681.2007.04816.x Macarthur DG; Seto JT; Chan S; Quinlan KGR; Raftery JM; Turner N; Nicholson MD; Kee AJ; Hardeman EC; Gunning PW; Cooney GJ; Head SI; Yang N; North KN, 2008, 'An Actn3 knockout mouse provides mechanistic insights into the association between α-actinin-3 deficiency and human athletic performance', Human Molecular Genetics, vol. 17, no. 8, pp. 1076 - 1086, http://dx.doi.org/10.1093/hmg/ddm380