With two new end-stations constructed and commissioned as part of the UPBL10 Upgrade project entering user operation, 2014 has seen both a major evolution in facilities available for Structural Biology at the ESRF and the coming to fruition of much hard work, spread over a number of years1. MASSIF-1 [ID30A-1] and MASSIF-3 [ID30A-3] provide new options for experiments in structural biology at ESRF.

Based around two ESRF-developed devices, the RoboDiff, which acts both as sample changer and goniometer and a high capacity dewar (HCD) that is capable of holding 240 SPINE standard sample holders, MASSIF-1 supplies for a new paradigm in structural biology: completely automatic, hands-off screening and/or data collection. Following a successful pilot study, such as service is now available to all our users and is proving extremely popular. MASSIF-3 is a fixed-energy end-station providing a highly intense (~2 x 1013 photons / second) microfocus (~15 µm diameter) X-ray beam at the sample position. This end-station is therefore ideal for the collection of diffraction data from microcrystals of biological macromolecules and, once the Eiger 4M detector associated with the end-station is operating at its full potential (750 Hz frame rate), will be an excellent vehicle for experiments exploiting the burgeoning technique of synchrotron serial crystallography (SSX).

The last element of the UPBL10 project will be put into place very shortly with the coming on stream of ID30B. This fully-tuneable end-station will offer both a high photon flux (~1013 photons/sec) and a variable spot size (20 to 200 µm2) at the sample position. In its final configuration, foreseen for mid-2015, ID30B will also provide access to in situ (i.e. in crystallisation plate) screening and data collection.

While the UPBL10 project is nearing its end, the long-term evolution of the facilities available for structural biology will continue. Indeed, the recently published ‘Orange Book’ contains many ideas for future facilities and experiments that will be enabled by the ultra brilliant X-ray beams that will be produced following the Phase II Upgrade of ESRF.

Our beamlines will also evolve in the medium term. Even as this piece is being written the mirrors making up the focussing optics of ID23-2 are being replaced. This should give a new lease of life to this pioneering microfocus end-station prior to the completion of a technical design report (TDR) aimed at producing, in 2016, an upgraded ID23-2 with a beamsize 1 µm, or less, in diameter at the sample position. Additionally, ideas for improving the functionality and X-ray beam characteristics on the two MAD beamlines ID23-1 and ID29 are actively being considered. The provision at the ESRF of techniques complementary to macromolecular crystallography continues to evolve: upgrade of the sample environment at the ID29-S Cryobench microspectroscopy facility is planned while the BioSAXS beamline BM29 will soon benefit from the installation of a new, more user-friendly on-line HPLC set-up. This, coupled with a multi-technique sample environment, will greatly improve the information available during BioSAXS experiments.

A strength of the Structural Biology Group has been its ability to continue to operate existing experimental facilities while at the same time constructing and commissioning new ones. The past year is no exception to this rule. Indeed, the number of ESRF-based depositions in the Protein Data Bank remains very high and covers a broad range of structural biology research. The highlights presented here illustrate that membrane proteins, either transporters or receptors, remain major targets of the research carried out at the Structural Biology Group’s beamlines as do studies aimed at understanding the molecular basis of disease. Concerning the latter, a particular highlight in 2014 was the elucidation, by Cusack and colleagues, of the crystal structures of the polymerases of bat-specific influenza A and human influenza B in complex with single stranded viral RNA promoter. Comparison of the two structures provides an atomic-level model of the mechanism of action of flu polymerases and may provide new insight into the design of anti-influenza drugs. The articles here also emphasise the increasing use of techniques (small-angle X-ray scattering, atomic force microscopy, in cristallo UV-visible or Raman spectroscopy) complementary to X-ray crystallography, a trend that is sure to grow in the coming years.

Finally, following a year’s sabbatical leave Sean McSweeney and Elspeth Gordon officially resigned their positions at the ESRF in September 2014. As Head of the Structural Biology Group from 2000 to 2013, Sean’s contribution to the success of the ESRF as an experimental resource for structural biology was extraordinary as was that of Elspeth in making use of synchrotron radiation an indispensible technique in the development of new pharmaceuticals. I’m sure that all readers of ESRF Highlights 2014 will want to join us in wishing Sean and Elspeth every success in their new ventures and in overcoming the challenges that lie ahead.

G. Leonard and C. Mueller Dieckmann


1. Although space does not allow acknowledgement of all those involved in the UPBL10 project, we would like to give a special mention here to technical staff of the Structural Biology Group (H. Caserotto, F. Dobias, T. Giraud, N. Guichard, M. Lentini, J. Soudarin, J. Surr), the staff of the EMBL Grenoble Outstation Synchrotron Instrumentation Group, the ESRF Beamline Control Unit (M. Guijarro, A. Beteva), the ESRF Data Analysis Unit (O. Svensson) and the staff of ESRF ISDD, particularly P. Theveneau and W. Schmid.