Scott Medler

Skeletal Muscle Design and Plasticity

Research Assistant Professor

PhD (1993-1998) Louisiana State University
Instructor (1998-1999) Louisiana State University
NIH Postdoctoral Fellow (2003-2003) Colorado State University
Assistant Biology Professor (2003-2004) Community College of Denver
Research Assistant Professor (2004-Present) University at Buffalo

Address Information

Scott Medler
Department of Biological Sciences
666 Cooke Hall
State University of New York at Buffalo
Buffalo, NY 14260
Phone: (716) 645-2363 Ext. 201
e-mail: smedler@buffalo.edu

RESEARCH SUMMARY

My focus is on the cellular and molecular organization, or design, of muscles and ultimately on how these properties change in response to development, exercise, and other demands. The physiological properties of muscles are derived from their cellular and molecular organization. All muscle work is based on myosin heavy chain motors that bind to actin filaments and pull them, eliciting muscle shortening. Within this common design, great diversity exists with respect to cellular organization and function. I am particularly interested in the organization of invertebrate muscles, because these muscle types are more diverse in their organization than those found in mammals. Muscles differ with respect to their specific assemblage of myofibrillar protein isoforms and with respect to their ultrastructural organization. During my graduate research I used electron microscopy and other techniques to study the ultrastructural organization of smooth muscles in bivalve molluscs. For the last several years, I have been using biochemical and molecular techniques to study muscle fiber organization and plasticity in crustacean muscles.

SELECTED PROJECTS

• Muscle Plasticity in Crustacean Muscles

I am interested in the establishment of different muscle types in developing lobster claw muscles. In early juvenile lobsters, the claw muscles of the paired claws are isomorphic: both are composed primarily of slow fibers surrounding a central core of fast muscle. Over subsequent molt cycles, the predominantly used claw differentiates into a large, heavy claw used for crushing prey items. At the same time, the contralateral claw becomes a much thinner claw used for catching prey and manipulating it. By adulthood, the larger claw (termed the crusher claw) is filled completely with slow muscle fibers, while the slimmer claw (termed the cutter claw) primarily possesses fast fibers. Precisely how this process of differentiation occurs is unclear, but it appears to be driven by an asymmetry at the level of the central nervous system. Over the last several years, I have been using biochemical and molecular techniques to study this process in juvenile and adult lobster muscles. It has turned out to be a more complex process than we had anticipated, in part because we discovered that even fully differentiated lobster muscles exhibit a high degree of polymorphism. That is, single muscle fibers often express multiple isoforms of myofibrillar proteins (for example, both fast and slow myosin heavy chain, MHC). Furthermore, we found that circulating levels of molting hormones (ecdysteroids) have little if any effect on myofibrillar gene expression. My interest is now turning to the relationship between fiber innervation pattern and muscle phenotype. The muscle fibers in the claw are controlled by two excitatory (one phasic and one tonic) motor neurons, and I am interested in the correlation between innervation pattern and the expression of alternate isoforms of MHC and other myofibrillar proteins.

• Scaling Effects on Muscle Organization in Terrestrial Crabs

A new project I am developing focuses on the effects of body size, or scale, on the organization of skeletal muscles in terrestrial 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). The precise causes for this scaling effect has been a matter of debate among biologists for decades, but remain obscure. However, one of the contributing factors stems from small animals possessing 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 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. In this project, I will measure changes in stride frequency in running crabs as a function of body size and investigate the cellular and molecular correlates in isolated skeletal muscles. I anticipate that both the ultrastructural organization and protein isoform assemblage in the muscles are fine-tuned as the crabs grow. Transmission electron microscopy is used in conjunction with stereological methods to quantify ultrastructural changes and standard biochemical and molecular techniques are used to monitor changes in isoform assemblage.

 

• Single Fiber Polymorphism in Mouse Muscle

I am also beginning a project focusing on single fiber polymorphism in mammalian muscles. As with lobster muscles, recent studies in mammalian models have found that single fibers predominantly 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 most 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 allowing fiber polymorphism? 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 can be monitored with quantitative PCR and muscle phenotype can be determined using protein gels. I anticipate 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.

SELECTED PUBLICATIONS