Muscle Biology Laboratory
- Professor Kay Ohlendieck;
Tel: (353-1) 708 3842; Fax: (353-1) 708 3845;- kay.ohlendieck@nuim.ie
- Research Profile
Research Interests:
The functional performance of skeletal muscle is based on refined physiological mechanisms that couple the electrical depolarisation of the surface membrane to motor protein activation, generally referred to as excitation-contraction coupling. Our laboratory focuses on the biochemical and physiological characterisation of supramolecular membrane complexes involved in the regulation and stabilisation of this relatively unique signal transduction mechanism. In mature fast fibres, direct physical coupling between the voltage-sensing receptor of the transverse tubules and the calcium release channel complex of the sarcoplasmic reticulum initiates contraction, while the energy-dependent re-uptake of calcium ions causes muscle relaxation. Using blot overlay assays with conjugated proteins, two-dimensional gel electrophoresis and chemical crosslinking and various immunochemical techniques we are characterising the role of protein-protein interactions in ion homeostasis.
Muscle fibres exhibit enormous plasticity and can adapt efficiently to changes in activity by atrophy, hypertrophy and/or fibre type shifting. Employing chronic low-frequency electro-stimulation to fast fibres, we are studying the effect of the fast-to-slow transition process on isoform expression patterns of key muscle proteins. Diseases affecting muscle proteins usually have devastating consequences for the organism, i.e. muscular dystrophy or sarcopenia of old age. To elucidate the molecular pathogenesis of these diseases, we are examining naturally occurring animal models, such as the dystrophic mdx mouse. The long-term aim of our laboratory is to make major advances in the understanding of excitation-contraction coupling by focussing on the elucidation of the molecular architecture of the triad junction, the molecular cell biology and functional interactions between ion-regulatory elements and on the pathophysiology of neuromuscular diseases arising from abnormalities in calcium handling. In conjunction with research networks funded by SFI and the European Commission, our laboratory is currently involved in a proteomics-based approach to identify all integral membrane proteins responsible for the assembly and maintenance of the junctional sarcoplasmic reticulum during myogenesis, transformation and ageing.
Science Foundation Ireland Principal Investigator grant; Health Research Board; European Commission; Muscular Dystrophy Ireland; Departmental Funding.