Citation | Malcolm Irving has made fundamental contributions to our understanding of the mechanism of muscle contraction through the application of time-resolved X-ray and optical techniques to measure the motion of `crossbridges' in muscle. His work has significantly strengthened the validity of the sliding filament hypothesis first formulated in 1954 and the concept of crossbridges as independent force transducers. Following the studies of HE Huxley and RM Simmons, he has radically enhanced low-angle diffraction studies of muscle by improving time-resolution to 20 µs and by making the measurements on single fibres. This has enabled him to assign discrete structural changes to the elastic and force-development phases of mechanical transients identified by AF Huxley and Simmons. He has pioneered the use of optical probes in muscle fibres, particularly in relation to specific structural information about crossbridge movement. In his most recent studies two-point attachment of a fluorescent probe at defined sites in myosin identified from crystal structures has enabled him to measure real-time motion of force-generating crossbridges. This approach to analysing molecular motion has broad implications as a general method for defining protein conformational changes. |