(Head of Laboratory)
Maria Antonietta Pellegrino
(MD, Sport Medicine Centre)
Skeletal muscle plasticity in health and disease
Skeletal muscle shows a high structural and functional heterogeneity and a high degree of plasticity, namely its structure and function can deeply adapt to physiologic and pathologic conditions such as exercise training, disuse, ageing, muscular dystrophy, chronic non muscle diseases, drug administration. Skeletal muscle plasticity is of paramount importance to enable the body to improve or simply maintain physical performance, and to cope with changes in energy and amino acid supply such as those occurring in starvation or chronic diseases. Our research group has been working since the 80s on the cellular and molecular mechanisms underlying skeletal muscle plasticity in health and disease.
To achieve our goal we combine the analyses of muscle structure and function in both humans and small mammals. The functional analysis of force and shortening velocity are performed at all levels of organisation: whole body; isolated muscles in vitro; individual muscle fibres; isolated myosin. The samples used for functional analysis can be subjected to the following structural analyses: (i) muscle fibres size and type by immuno-histochemistry; (ii) concentration of myosin and myofibrillar proteins by quantitative electrophoresis; (iii) expression of myofibrillar proteins isoforms by high resolutions SDS-PAGE and Western blot; (iv) global protein pattern and post-translational modifications of proteins by proteomics; (v) intracellular signalling pathways controlling muscle mass and metabolism.
We have given a relevant contribution to: (i) the understanding of the role of myosin isoforms in determining the contractile and energetic properties of skeletal muscle fibres; (ii) the identification of the molecular mechanisms underlying myosin isoform functional diversity; (iii) the understanding of the mechanisms underlying the functional adaptation to exercise, ageing, disuse and muscular dystrophy.
Selected PapersUltrafast force-clamp spectroscopy of single molecules reveals load dependence of myosin working stroke. Capitanio M, Canepari M, Maffei M, Beneventi D, Monico C, Vanzi F, Bottinelli R & Pavone FS. (2012). Nature methods 9, 1013-1019.
The role of alterations in mitochondrial dynamics and PGC-1alpha over-expression in fast muscle atrophy following hindlimb unloading. Cannavino J, Brocca L, Sandri M, Grassi B, Bottinelli R & Pellegrino MA. (2015). J Physiol. 593, 1981-1995.
Human skeletal muscle fibre contractile properties and proteomic profile: adaptations to 3 weeks of unilateral lower limb suspension and active recovery. Brocca L, Longa E, Cannavino J, Seynnes O, de Vito G, McPhee J, Narici M, Pellegrino MA & Bottinelli R. (2015). J Physiol 593, 5361-5385.