Office: Biotechnology Center Rm. 2111
Rensselaer Polytechnic Institute
110 8th Street
Troy, NY 12180
Muscle physiology, motor protein biophysics, muscle and heart diseases.
My laboratory investigates the molecular mechanisms that enable muscle to perform an amazingly wide variety of tasks including powering flight, swimming, and blood circulation. These different modes and velocities of movement are made possible by different muscle fiber types. How variation in the mechanical properties of muscle fiber types is determined by muscle proteins is a major focus of my lab. We are particularly interested in the role of myosin, the molecular motor that powers muscle contraction by converting the chemical energy in ATP to force and motion through a series of kinetic and mechanical steps known as the cross-bridge cycle. Different isoforms of myosin (versions) are a major determinant of how fast a muscle fiber type shortens and how much force it can generate. We investigate which structural regions of myosin are critical for setting these properties using our model organism, Drosophila (fruit flies).
We take an integrative approach, starting with manipulating muscle genes and moving up in scale to protein expression and function, muscle mechanics, and whole organism studies. This comprehensive approach is possible by taking advantage of the unique genetic techniques available with Drosophila. For example, we can express a modified myosin gene in Drosophila to produce altered myosin protein in its flight muscle. The altered myosin protein can be isolated from Drosophila flight muscle to measure biochemical, biophysical and single molecule properties. We can also measure the mutated myosin’s impact on flight muscle mechanical properties such as power, velocity and force production. We relate these altered fiber properties to observed changes in locomotion, such as wing beat frequency.
Some of the myosin structural regions we investigate are hot spots for point mutations that lead to familial hypertrophic cardiomyopathy, an atypical thickening of heart ventricular muscle that is a leading cause of sudden death in young adults. If we can understand how these regions are important for normal myosin function, we can learn why these mutations cause heart disease. We also directly investigate muscle diseases. For example, we are studying Drosophila muscle expressing a myosin with a point mutation that leads to myosin based inclusion body myopathy type 3. This human disease weakens fast contracting muscle fiber types.
My laboratory is also investigating the function of muscle LIM protein (MLP). Mutations in human MLP cause cardiac hypertrophy. Our experiments suggest MLP’s role is to maintain proper muscle stiffness, and that it may be involved in signaling for increased muscle protein expression in response to increased muscle use. We have started investigating the contribution of the muscle regulatory protein troponin to stretch activation. Stretch activation is a mechanism used by insect flight muscle and heart muscle to increases the amount of force and power generated during each contraction cycle. Understanding the molecular basis of stretch activation could lead to methods to restore function to failing hearts. Another recent project is a collaboration with Dr. Corr in RPI’s Department of Biomedical Engineering to develop methods of growing muscles and tendons in culture for wound repair.
Swank, D.M. (2012) Mechanical analysis of Drosophila indirect flight and jump muscles. Methods 56: 69-77.
Wang, Q., C. Zhao and D.M. Swank (2011) Calcium and stretch-activation modulate power generation in Drosophila flight muscle. Biophysical Journal 101: 2207-2213.
Ramanath, S., Q. Wang, W. A. Kronert, S. I. Bernstein and D. M. Swank (2011) Disrupting the myosin converter-relay interface impairs Drosophila indirect flight muscle performance. Biophysical Journal 101: 1114-1122.
Clark, K.A., H. Lesage, C. Zhao, M. Beckerle and D. M. Swank (2011) Deletion of Drosophila muscle LIM protein decreases flight muscle stiffness and power generation. Amer. J. Physiol.-Cell 301: C373-C382.
Purcell, T. J., N. Naber, K. Franks-Skiba, A. R. Dunn, C. C. EldredG, C. L. Berger, A. Malnasi-Csizmadia, J. A. Spudich, D. M. Swank, E. Pate, and R. Cooke. (2011). Nucleotide pocket thermodynamics measured by EPR reveal how energy partitioning relates myosin speed to efficiency. J. Mol. Biol. 407:79-91.
Yang, C., C. Kaplan, M. Thatcher and D. M. Swank (2010) The influence of myosin converter and relay domains on cross-bridge kinetics of Drosophila indirect flight muscle. Biophysical Journal 99:1546-1555.
Eldred, C.C. D.R. Simeonov, R.A. Koppes, C. Yang, D.T. Corr and D.M. Swank (2010) The mechanical properties of Drosophila jump muscle expressing wild-type and embryonic myosin isoforms. Biophysical Journal 98:1218-1226.
Miller, M.S., C. M. Dambacher, A. F. Knowles, J. M. Braddock, G. P. Farman, T. C. Irving, D. M. Swank, S. I. Bernstein and David W. Maughan (2009) Alternative S2 hinge regions of the myosin rod affect myofibrillar structure with minor alterations in myosin kinetics. Biophysical Journal 96:4132-4143.
Kronert, W.A., C.A. Dambacher, A.F. Knowles, D.M. Swank and S.I. Bernstein (2008) Alternative relay domains of Drosophila melanogaster myosin differentially affect ATPase activity, in vitro motility, myofibril structure and muscle function. J. Mol. Biol. 379:443-456.
Yang, C., S. Ramanath, S. I. Bernstein, D. W. Maughan and D. M. Swank (2008) Alternative versions of the myosin relay domain differentially respond to load to influence Drosophila muscle kinetics. Biophysical Journal (in press).
Swank, D.M., V. Vishnudas and D.W. Maughan (2006) An exceptionally fast actomyosin reaction powers insect flight muscle. Proc. Natl. Acad. Sci. 103:17543-17547.
Swank, D.M., J. Braddock, W. Brown, H. Lesage, S.I. Bernstein, and D.W. Maughan (2006) An alternative domain near the ATP binding pocket of Drosophila myosin affects muscle fiber kinetics. Biophys. J. 90:2427-2435.
Liu, H., M.S. Miller, D.M. Swank, W.A. Kronert, D.W. Maughan and S.I. Bernstein (2005) Paramyosin phosphorylation site disruption affects indirect flight muscle stiffness and power generation in Drosophila melanogaster. Proc. Natl. Acad. Sci. 102:10522-10527.
Miller, B.M., S. Zhang, J.A. Suggs, D.M. Swank, K.P. Littlefield, A.F. Knowles and S.I. Bernstein (2005) An alternative domain near the nucleotide-binding site of Drosophila muscle myosin affects ATPase kinetics. J. Mol. Biol. 353:14-25.
Swank, D.M. and J.O. Vigoreaux (2004) The development of the flight and leg muscle. In: Comprehensive Molecular Insect Science, L.I. Gilbert, K. Iantrou and S.S. Gill (eds.) Elsevier Science Ltd. Oxford, UK.
Littlefield, K.M., D.M. Swank, B. Sanchez, A.F. Knowles, D. M. Warshaw, and S.I. Bernstein* (2003) The converter domain modulates the kinetic properties of Drosophila myosin. Amer. J. of Physiol.-Cell 284:C1031-C1038.
Swank, D.M., A.F. Knowles, W.A. Kronert, J.A. Suggs, G.E. Morrill, M. Nikkoy, G.G. Manipon, and S.I. Bernstein (2003) Variable N-terminal regions of muscle myosin heavy chain modulate ATPase rate and actin sliding velocity. J. Biol. Chem. 278:17475-17482.
Swank, D.M., A.F. Knowles, F. Sarsoza, J.A. Suggs, D.W. Maughan and S.I. Bernstein (2002) The myosin converter domain modulates muscle performance. Nature Cell Biology 4: 312-317.
Swank, D.M., M.L. Bartoo, A.F Knowles, C. Iliffe, S.I. Bernstein, J.E. Molloy, and J.C. Sparrow (2001) Alternative exon-encoded regions of Drosophila myosin heavy chain modulate ATPase rates and actin sliding velocity. J. Biol. Chem 276: 15117-15124.
Swank, D.M. and L.C. Rome (2001) The influence of thermal acclimation on power production during swimming II: mechanics of scup red muscle under in vivo conditions. J. Exp. Biol. 204: 419-430.
Swank, D.M., L. Wells, W.K. Kronert, G. Morrill and S.I Bernstein (2000) Determining structure/function relationships for sarcomeric myosin heavy chain by genetic and transgenic manipulation of Drosophila. Microscopy Res. and Tech. 50: 430-442.
Swank, D.M. and L.C. Rome (1999) The influence of temperature on power production during swimming I. in vivo length change and stimulation pattern. J. Exp. Biol. 203: 321-331.
Swank, D.M., G. Zhang, and L.C. Rome (1997) Contraction kinetics of red muscle in scup: mechanism for variation in relaxation rate along the length of the fish. J. Exp. Biol. 200: 1297-1307.
Swank, D.M. and L.C. Rome (1996) Effects of SR calcium pump inhibition on relaxation and power from scup red muscle. Biol. Bull. 191: 267-268.
Rome, L.C., D.M. Swank and D. Corda (1993) How fish power swimming. Science 261: 340-343.