Introduction
Macromolecular crystallography has continued to play a dominant role in the Life Sciences during 2001. ID29 was inaugurated into the public programme as a beamline with a full capacity for multi-wavelength anomalous diffraction (MAD) experiments, replacing the bending magnet beamline BM14. The new beamline has already provided some impressive results (see for example the research of Iwata et al., on the structure of the membrane protein, formate dehydrogenase). An in-vacuum insertion device will be installed for the beamline in the winter of 2001. BM14 has become a collaborating research group (CRG) facility, operated jointly by Spanish and UK consortia. At the beginning of 2003, the Spanish consortium will move to BM16, currently the powder diffraction beamline, which itself is being transferred to an insertion device, ID31. At BM16, the Spanish group will maintain macromolecular crystallography, but may also add other techniques such as small-angle X-ray scattering. Indeed, macromolecular crystallography will gain two thirds of a bending magnet beamline because the ESRF has one third of the use of the CRG beamlines for its public programme. The inauguration of the second branch of DUBBLE, the Dutch-Belgium CRG at BM26 will bring this figure up to a whole new beamline and this is in addition to the French CRG beamline FIP at BM30. In the ID14 Quadriga complex, station EH3 has been taken out of commission for refurbishment. It is being used to develop automation and high-throughput technologies that will then be transferred to the other beamlines.
This Highlights 2001 includes projects from both the in-house research programme, (Hybrid Cluster Proteins, the Semiliki Forest Virus and Phase Determination Using Anomalous Scattering from Sulphur Atoms) and the research of the external user community. With respect to the former, the programme under the leadership of Sean McSweeney continues to flourish resulting in the development of new technologies on the beamlines and in the methodology of data collection, processing and structure elucidation. With respect to the latter, the programmes on the cyanobacterial system and the ribosomal subunits deserve special mention. These are long-term projects that require repeated visits to synchrotron radiation facilities. In the case of the ribosomal subunits, many thousands of crystals, by several groups, have been used to produce the present-day results. Such research requires dedication and the long-term support that has become possible through the Block Allocation System and Long Term Project research programmes. Every year it becomes more difficult to select highlights in the field of macromolecular crystallography. The overall quality and importance of these structural studies is astonishingly high and any selection becomes very subjective. If your research is not mentioned, this reflects the judgement of the Research Directors and not its quality.
It should be noted that the use of the macromolecular crystallography beamlines by the pharmaceutical industry continues to increase. A beamline (or its equivalent) dedicated to this type of use and incorporating a "Fedex" service (send crystals, receive data or even structures) will clearly be needed in the near future. The income derived from such a beamline could well fund staff and other projects. New projects include the Partnership for Structural Biology involving the ILL, the EMBL Grenoble Outstation, the ESRF and maybe other institutions. This partnership intends to provide a technological and scientific base within the European context to exploit post-genomic research and high-throughput methodology. In its basic form, the partnership intends to build a new beamline complex dedicated to macromolecular crystallography and to construct a new building for both in-house use and use by external parties. The beamline complex will involve two beamlines one with full MAD capacity and the second with limited MAD capacity in the ID23 straight section of the ESRF. It may well involve the use of canted undulators to give two separate and distinct beams or a diamond monochromator in a similar manner to the Quadriga complex. Further details of this important and exciting new project can be obtained from the Management of the three institutions mentioned above.
Within the Life Sciences programme, and indeed in many other parts of the overall science programme at the ESRF, the use of micro X-ray beams is becoming increasingly important. Thus small, highly collimated X-ray beams can be used for small samples or small volumes of larger samples. In this respect beamline ID13 has pioneered a number of technical developments. These are illustrated by research into the structure of sensory rhodopsin and the microstructural homogeneity of support silk spun by Eriophora fuliginea.
The Biomedical programme is also expanding and a new biomedical facility has just been completed as an extension to the ID17 building. This will enable a whole new range of research activities to be instigated in addition to those in human coronary angiography, radiation dosimetry, phantom imaging and technological developments on the beamline. Thus, experiments will be performed to measure cerebral blood values and blood to brain transfer coefficients in the C6 glioma model in the rat brain and in the VX2 carcinoma model in the rabbit brain, to evaluate lung function in rabbits as part of an investigation into asthma, and to develop new protocols for therapy. In this Highlights 2001, research is presented from the microbeam radiation therapy programme, a long-term research project involving Jean Laissue and his team in Switzerland, which could lead to the radiation treatment of surgically inoperable brain and other tumours in humans. These types of experiment, undertaken in a humane manner by professionals, are essential for the progress of medicine. It should be clearly remembered that many medical treatments that are now accepted as normal and routine, could only have been developed through such programmes.
This Highlights 2001 is the last highlights for which I have had the pleasure of writing an introduction to the Life Sciences section. The past five years have seen many changes including the dedication of ID2 to small-angle scattering, the development of ID13, the Quadriga complex and ID29, and of course, the Biomedical programme. The Life Sciences are also being practised elsewhere: EXAFS on ID26; X-ray microscopy on ID21 and ID22; and tomography on ID19. Currently the Life Sciences account for some 20-25% of the overall science programme at the ESRF. I have enjoyed my period of office at the ESRF and hope that the Life Sciences will continue to expand and flourish, producing research that is acknowledged to be at the forefront of world science. Of course, the Life Sciences cannot be allowed to dominate resources at the expense of other important programmes in materials science and physics. I hope that my colleagues in the life sciences will be both tolerant and broad in outlook, thereby accepting that the ESRF and other synchrotron sources in Europe must be allowed to serve science as a whole.
Peter Lindley
Director of Research December 2001