Citation | Holmes has played a leading role in developing new experimental and theoretical methods for extracting structural information from biological fibres by x-ray diffraction. Initially in collaboration with the late Rosalind Franklin and with Klug, and later with his own team in Heidelberg, he has analysed the structure of oriented gels of tobacco mosaic virus, and recently obtained an electron density map at A Ao resolution. This is the first high-resolution electron density map obtained from the x-ray fibre diagram of a macromolecular assembly, and it allowed the general stereochemical nature of the protein-RNA interaction to be determined. The work necessitated a quantitative analysis of fibre diagrams using isomorphous substitution in a way not previously attempted, and was made possible by the equipment developed and built by Homes for the production and microdensitometry of this type of diffraction photograph. He made important advances in the applications of focussing monochromators and has had a long involvement in the development of intense x-ray sources. With Longley he produced the first fine-focus rotating anode x-ray tube which formed the basis for the commercially successful Elliott design, and with Huxley he introduced the 'Big Wheel' also produced by Elliot's. He was among the first to realise the possibilities of synchrotron radiation as a very intense x-ray source, and he and his group were the first to demonstrate this potential experimentally. These initiatives culminated in the building of a laboratory at the Deutsches Elektronensynchrotron in Hamburg for the exploitation of this technique in biology, a concept which has since been taken up by a number of other groups around the world. The method has been successfully applied by Holmes and his collaborators to a detailed study of changes in the configuration of the cross-bridges of insect flight muscle induced by ATP and other nucleotides; such changes were first seen by him in 1965 and provided the first demonstration of a change in angle of the cross-bridges between different states of the muscle, a very important result. |