|2005 -||Honorary Visiting Professor||Department of Biology, University of York|
|1987 - 2004||EMBL Fellow and Staff Scientist||European Molecular Biology Laboratory, Heidelberg|
|1979 - 1986||Principal Scientific Officer||Institute of Animal Physiology Babraham, Cambridge|
|1970 - 1979||Senior and Principal Scientific Officer||Department of Zoology, Oxford|
|1978||PhD||University of Cambridge|
|1965 - 1969||Research Physiologist||Department of Physiology, University of California Los Angeles|
Muscles are activated by calcium and, in addition, striated muscles are stretch-activated. When an active muscle is stretched, it produces more tension. This type of regulation is important in cardiac muscle and the indirect flight muscle of insects.The mechanism by which fibres sense stretch is not known, despite its importance for understanding muscle contraction, and the application to cardiomyopathies. We aim to find out how stretch activation works at the molecular level, using flight muscle as a model system. The water bug, Lethocerus, is used to study flight muscle proteins and fibre mechanics, and Drosophila to study the function of proteins in vivo. In striated muscle, the interaction of myosin with actin is controlled by tropomyosin and troponin on actin filaments. There is recent evidence that, in insect flight muscle, a pull on troponin can move tropomyosin from a blocking position on actin. Force may be transmitted by ‘troponin bridges’ linking myosin and actin filaments. We are investigating the interaction of subunits within the troponin complex, as well as the association of troponin with other muscle proteins, and changes in the structure occurring on binding calcium or when the muscle is stretched.
Both flight and cardiac muscles are unusually stiff, which enables them to sense small stretches. Large titin-like proteins containing chains of immunoglobulin domains are responsible for the high stiffness; the proteins also have a signalling function and are needed for correct assembly and maintenance of sarcomere structure. We have characterized sallimus (Sls) in Drosophila flight muscle and shown that it links myosin filaments to the Z-disc. We are now studying Drosophila obscurin, which is in the M-line region in the middle of the flight muscle sarcomere. Obscurin is necessary for the assembly of myosin and actin filaments with the correct symmetry. We have identified ligands binding to two kinase domains in the protein, both of which are part of a signalling pathway involved in myogenesis.
Eldred, C. C., Katzemich, A., Patel, M., Bullard B. and Swank, D. (2014). The roles of troponin C isoforms in the mechanical function of Drosophila indirect flight muscle. J. Muscle Res. Cell Motil. 35, 211-223.
Katzemich, A., Kreisköther, N., Alexandrovich, A., Elliott, C., Schöck, F., Leonard, K., Sparrow, J. and Bullard, B. (2012). The function of the M-line protein obscurin in controlling the symmetry of the sarcomere in the flight muscle of Drosophila. J. Cell Sci. 125, 3367-3379.
Bullard, B and Pastore, A. (2011). Regulating the contraction of insect flight muscle. J. Muscle Res. Cell Motil. 32, 303-313.
De Nicola, G.F., Martin, S., Bullard, B. and Pastore, A. (2010). Solution structure of the apo C-terminal domain of the Lethocerus F1 troponin C isoform. Biochemistry, 49, 1719-1726.
Krzic, U., Rybin, V., Leonard, K.R., Linke,W.A. and Bullard, B. (2010). Regulation of oscillatory contraction in insect flight muscle by troponin. J. Molec. Biol. 397, 110-118.
Boussouf, S., Agianian, B., Bullard, B. and Geeves, M. (2007). The regulation of myosin binding to actin filaments by Lethocerus troponin. J. Molec. Biol. 373, 587-598.
Burkart,C., Qiu, F., Brendel, S., Benes, V., Hååg, P., Labeit, S., Leonard, K. and Bullard, B. (2007). Modular proteins from the Drosophila sallimus (sls) gene and their expression in muscles with different extensibility. J. Molec. Biol. 367, 953-969.
De Nicola, G. Burkart, C., Qiu, F., Agianian, B., Labeit, S., Martin, S., Bullard, B. and Pastore, A. (2007). The structure of Lethocerus troponin C: Insights into the mechanism of stretch activation in muscles. Structure, 15, 813-824.