The long term goal of my research program is to understand the design of muscular systems. This involves performing experiments that facilitate the integration of information from molecular, cellular and whole animal studies. This approach is unusual and important because scientists generally work either on molecules, cells or whole animals but not on all three. This approach is crucial because there are large gaps in our knowledge of the principles by which animals use their muscles. An ultimate goal of this integrative approach is to understand enough about the molecular (e.g., crossbridges, Ca pumps) and macroscopic (e.g., joints, muscle arms) components of muscular systems, so that we can develop a comprehensive model that enables us to understand and predict how alterations in one parameter (e.g., crossbridge detachment rate) might affect motor performance. With the recent developments in biophysical, whole animal, and musculo-skeletal modeling techniques, we are for the first time in the position where we can relate molecular properties (e.g., crossbridge kinetics) to whole animal function in meaningful way. The frog, Rana pipiens, presents a superb model to proceed to this level. First, the jumping muscles are nearly pure in fiber type, and all the fibers are maximally recruited during jumping. Further, frog fibers are amenable to biophysical techniques, and jumping is amenable to biomechanical analysis. Our goal will be to 1) measure the sarcomere length changes and activation pattern of the major extensor muscles during jumping, 2) drive the isolated muscles through these in vivo length changes and stimulation pattern, and measure the resulting force and power output, 3) construct an anatomically and physically accurate model of the frog muscular system. This """"""""virtual animal"""""""" will enable us to transduce our understanding of isolated muscle to whole animal locomotion and to test specific hypotheses about the design of the frog muscular system. 4) We will make a series of biophysical measurements on frog muscle fibers from which we will construct a simple molecular-based model of muscle which can be integrated into the overall model of the frog. We will then manipulate molecular properties in the model and observe the effect on jumping performance. Ultimately, elucidation of the principles of how healthy motor systems work may be useful in 1) understanding disease/injuries of the motor/cardiovascular systems, 2) designing computer systems for aiding movement in the handicapped, 3) designing pharmacological and genetic interventions for muscle disease states, 4) understanding the functional basis of training/ rehabilitation, 5) choosing appropriate skeletal muscle for heart pumping assist.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR046125-05
Application #
6659850
Study Section
Special Emphasis Panel (ZRG1-GMA-2 (01))
Program Officer
Nuckolls, Glen H
Project Start
1999-09-01
Project End
2006-08-31
Budget Start
2003-09-01
Budget End
2006-08-31
Support Year
5
Fiscal Year
2003
Total Cost
$309,197
Indirect Cost
Name
University of Pennsylvania
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Harwood, Claire L; Young, Iain S; Tikunov, Boris A et al. (2011) Paying the piper: the cost of Ca2+ pumping during the mating call of toadfish. J Physiol 589:5467-84
Kargo, William J; Ramakrishnan, Arun; Hart, Corey B et al. (2010) A simple experimentally based model using proprioceptive regulation of motor primitives captures adjusted trajectory formation in spinal frogs. J Neurophysiol 103:573-90
Tikunov, Boris A; Rome, Lawrence C (2009) Is high concentration of parvalbumin a requirement for superfast relaxation? J Muscle Res Cell Motil 30:57-65
Elemans, Coen P H; Mead, Andrew F; Rome, Lawrence C et al. (2008) Superfast vocal muscles control song production in songbirds. PLoS One 3:e2581
Rome, Lawrence C (2007) The effect of temperature and thermal acclimation on the sustainable performance of swimming scup. Philos Trans R Soc Lond B Biol Sci 362:1995-2016
Tikunov, Boris A; Rome, Lawrence C (2007) Controlling the freezing process: a robotic device for rapidly freezing biological tissues with millisecond time resolution. Cryobiology 55:93-7
Rome, Lawrence C (2006) Design and function of superfast muscles: new insights into the physiology of skeletal muscle. Annu Rev Physiol 68:193-221
Klimov, A A (2006) [Measuring real-time sarcoplasmic reticulum calcium pumping in skinned muscle fibers] Biofizika 51:844-51
Rome, Lawrence C; Flynn, Louis; Goldman, Evan M et al. (2005) Generating electricity while walking with loads. Science 309:1725-8
Nguyen, Taitan; Rubinstein, Neal A; Vijayasarathy, Camasamudram et al. (2005) Effect of chronic obstructive pulmonary disease on calcium pump ATPase expression in human diaphragm. J Appl Physiol 98:2004-10

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