Hugh Huxley, Ph.D. Professor of Biology Muscle Contraction Ph.D., Christ's College, Cambridge and M.R.C. Laboratory of Molecular Biology
	huxley@auriga.rose.brandeis.edu (781) 736-2490

Our research is intended to elucidate the mechanism by which force is developed by the interaction of myosin and actin molecules in muscle and in a number of other motile systems. We use primarily structural approaches, and focus on the dynamics of the changes taking place in the crossbridges in striated muscle during contraction. It has long been established that muscle contraction is brought about by a sliding filament mechanism, in which partially overlapping arrays of actin and myosin filaments are acted on by a relative sliding force which leads to shortening of the muscle. It is generally believed that this force is generated by a cyclic interaction of myosin crossbridges with sites on the actin filaments. However, the structural details of the process have proved to be particularly difficult to establish, partly because of the transient and unsynchronized nature of many of the changes taking place, and partly because of the technical difficulty of obtaining submicroscopic structural information about any rapidly changing biological system. In recent years, a number of new approaches to this problem have been used, and amongst these time-resolved low angle X-ray diffraction studies of intact muscle have played an important part. The power of these X-ray methods is advancing rapidly as improved facilities come on stream for the generation of intense X-ray beams using synchrotron radiation sources at such centers as Brookhaven and Stanford, and as improved data-collecting systems are developed. We are exploiting these possibilities to obtain much more structural and kinetic information about the behavior of the attached crossbridges as they go through their cycles of operation and about the on-off switching mechanism of muscle.

Selected Publications:

Huxley, H.E. (2002) "Max Perutz (1914-2002)" in "News & Views," Nature 415:851-852.

Huxley, H.E., Reconditi, M., Stewart, A., and Irving, T. (2002) "Crossbridge and backbone contributions to interference effects on meredional X-ray reflections." Biophys. J. 82:5A.

Reconditi, M. Huxley, H.E., Stewart, A., and Irving, T. (2001) "The meredional profile of the M3 reflection during tension onset in skeletal muscle." Biophys. J. 80:267A.

Huxley, H.E., Reconditi, M., Stewart, A., Irving, T., and Fischetti, R. (2001) "Use of X-ray interferometry to steady crossbridge behaviour during rapid mechanical transients." Biophys. J. 80: 266A.

Huxley, H.E., Reconditi, M., Stewart, A., and Irving, T. (2000) "Changes in the 5.9 and 5.1 mm actin layer lines during contraction and quick release." Biophys. J. 78: 232A.

Huxley, H.E., Reconditi, M., Stewart, A., and Irving, T. (2000) "Interference changes on the 14.5 mm reflection during rapid length changes." Biophys. J. 78: 134.

Huxley, H.E., Reconditi, M., Stewart, A., and Irving, T. (2000) "Behaviour of the 14.5 mm reflection during force development." Biophys. J. 78: 228A.

Huxley, H.E., Reconditi, M., Stewart, A., and Irving, T. (1999) "X-ray evidence for changes in configuration of actin-attached myosin heads during the working stroke in intact muscle." Biophys. J. 76: 269A.

Huxley HE. (2000) Past, present and future experiments on muscle. Philos Trans R Soc Lond B Biol Sci. 355:539-43. [abstract]

Huxley HE, Stewart A, Irving T. (1998) Spacing changes in the actin and myosin filaments during activation, and their implications. Adv Exp Med Biol. 453:281-7; discussion 287-8.

Huxley HE. (1998). Getting to grips with contraction: the interplay of structure and biochemistry. Trends Biochem Sci. 23:84-7.

Huxley, H.E. 1996. A personal view of muscle and motility mechanisms. Annu. Rev. Physiol. 58:1-19. [abstract]

Huxley, H.E., Stewart, A., Sosa, H., and Irving, T. 1994. X-ray diffraction measurements of the extensibility of actin and myosin filaments in contracting muscle. Biophys. J. 67: 2411-2412. [abstract]

Sosa, H., Popp, D., Ouyang, G. and Huxley, H.E. 1994. Ultrastructure of skeletal muscle fibers studied by a plunge quick freezing method: Myofilament lengths. Biophys. J. 67: 283-292. [abstract]

Huxley, H.E., Kress, M. Faruqi, A.R. and Simmons, R.M. 1988. X-ray diffraction studies of muscle during rapid shortening in Molecular Mechanism of Muscle Contraction. Ed. Sugi & Pollack. Plenum Press, N.Y. pp. 347-352.

Kress, M., Huxley, H.E., Faruqi, A.R. and Hendrix, J. 1986. Structural changes during activation of frog muscle studied by time-resolved X-ray diffraction. J. Molec. Biol. 188:325-342.

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