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Dr. Scott Medler

Research Assistant Professor
666 Cooke Hall
Phone: (716) 645-4941
e-mail: smedler@buffalo.edu
Further research info

Research Summary

My focus is on the cellular and molecular organization of skeletal muscles and how these properties change in response to development, exercise, and other demands. The physiological properties of muscles are primarily derived from their cellular and molecular organization. All muscle work is based on muscle shortening, produced when myosin heavy chain motors bind to actin filaments and pull them. Yet within this common design, great diversity exists with respect to cellular organization and function. I am particularly interested in the organization of skeletal muscles from the standpoint of task-specific design, and the integration with organismal function. Muscles differ with respect to their specific assemblage of myofibrillar protein isoforms, including multiple isoforms of motor proteins (myosins) and of the regulatory proteins (tropomyosin and troponins I, T, and C) that function to switch the muscle on and off.  My research seeks to understand how these various isoforms are matched with one another to create a specific muscle phenotype.  Recent research demonstrates that single muscle fibers possess a continuum of phenotypes, suggesting that muscles have the capability to be ‘fine-tuned’ to produce a precise type of contractile output. 

• Scaling Effects on Muscle Organization in Terrestrial Crabs

Over the past few years we have been examining the effects of body size, or scale, on the organization of skeletal muscles in terrestrial ghost crabs. For centuries, people have been aware that small animals tend to move with faster limb movements than large animals (imagine the limb frequency of a running mouse versus a running horse). We have found that stride frequency declines as the crabs grow larger, with large animals (> 45 g) running at ~ 5 hz and small animals (< 10 g) at ~ 8 hz. The precise causes for this scaling effect has been a matter of debate among biologists for decades, but seems to stem from the natural frequency of the limbs. Whatever the precise mechanisms involved, one of the outcomes is that muscles from small animals possess faster contracting muscles than their larger counterparts. In animals with indeterminate growth, what are the cellular and molecular adjustments to the muscles that cause them to slow with increasing size? Many species of terrestrial ghost crabs possess running abilities that rival similar sized vertebrates and a single species has individual animals differing in body mass by an order of magnitude or more. We are making measurements of muscle function in running crabs and determining the molecular organization of the skeletal muscles that drive locomotion. These muscles express three different isoforms of the myosin heavy chain (MHC) molecule that is the motor protein in the muscles. Subtle changes in the expression of these alternate isoforms may allow the kinetic properties of the muscles to be fine-tuned as the crabs grow.

• Single Fiber Polymorphism in Mouse Muscle

We are currently working on a project focusing on single fiber polymorphism in mammalian muscles. During my postdoctoral research, I discovered that many lobster muscle fibers co-express multiple isoforms of MHC and other myofibrillar proteins. Similarly, recent studies in mammalian models have found that single fibers in many rodent muscles co-express multiple isoforms of MHC. Just a few years ago, such co-expression was taken as a sign that the fibers were in the process of switching from one type to another. Skeletal muscles are highly plastic tissues and this type of fiber type switching does take place, but newer findings that many fibers are polymorphic challenges our understanding of basic muscle biology. Since mammalian skeletal muscle fibers are under the control of a single motor neuron, what are the mechanisms responsible for fiber polymorphism? We are currently assessing the relative abundance of polymorphic fibers in specific mouse muscles and investigating the relative stability of these phenotypes. One area of interest is the influence of different types of stimuli, such as eccentric and concentric muscle contraction on the expression of specific MHC isoforms. Following an exercise protocol, isoform specific expression is monitored with quantitative PCR and muscle phenotype can be determined using histochemistry and single fiber protein gels. One hypothesis is that exercise acts to reduce fiber polymorphism, by eliciting the expression of predominantly one MHC isoform over the others. Determining the factors that influence skeletal muscle phenotype is central to our basic understanding of muscle responses to exercise and disease.

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Identification of muscle fiber types. (Above) Histochemical staining (ATPase) is used to identify muscle fiber types. In this image, slow fibers are dark, while fast fibers are light. (Below) Monoclonal antibodies to slow (type I) MHC identify the slow fibers in a serial section. (mouse gastrocnemius muscle)		Kinematic analyses are used to determine muscle function in vivo. (Above) Ghost crab running on treadmill. (Middle) Anatomical measurement of muscles. (Below) Angular velocity translates into muscle shortening velocity.

MHC isoforms identified with SDS PAGE (Left) Four adult MHC isoforms can be identified in rodent muscles. (Right) This technique is used to identify MHC content in single mouse fibers. The fiber sample second from the left is a hybrid X/B fiber (triceps).

Selected Publications

• Perry, MJ, Tait, J, Hu, J, White, SC, and Medler, S. (2009) Skeletal muscle fiber types in the ghost crab, Ocypode quadrata: implications for running performance. Journal of Experimental Biology 212: 673-683. Article

• Medler, S and Hulme, K (2009). Power output from striated muscles performing cyclical contractions: patterns and constraints. Comparative Biochemistry and Physiology 152A: 407-417. Article

• Medler S, Lilley T R, Riehl J H, Mulder E P, Chang E S, and Mykles D L (2007). Myofibrillar gene expression in differentiating lobster claw muscles.  Journal of Experimental Zoology 307A: 281-295. Article

• Medler S, Lilley T, and Mykles, DL (2004) Fiber polymorphism in lobster
  skeletal muscles: continuum between slow phasic (S₁) and slow tonic (S₂) muscle fibers. Journal of Experimental Biology 207: 2755-2767 Article

• Medler S (2002) Comparative trends in shortening velocity and force production
  in skeletal muscles. American Journal of Physiology Regulatory Integrative Comp Physiol 283: R368-R378. Article