The completion of Phase I of the ESRF Upgrade project in December 2015 has marked a major milestone for the ESRF Structural Biology Group. The four beamlines MASSIF-1 [ID30A-1], MASSIF-3 [ID30A-3], BM29 and ID30B constructed as part of the UPBL10 project and designed to replace the almost mythical ID14 are now all in full operation, both increasing the functionality available to the ESRF Structural Biology User Community [1, 2] and ensuring that sufficient beamtime can be allocated for even the most challenging of projects. The new functionality available is impressive. BM29 is the state-of-the-art facility for BioSAXS while MASSIF-1 offers an increasingly popular hands-off, completely automatic diffraction data collection and, if necessary, structure solution service (see S. Kharde et al. [3] for an example of what is possible without any direct user intervention). The more recently commissioned MASSIF-3 – where we expect an Eiger 4M detector capable of operating at a maximal frame rate of 750 Hz to be available to users from spring 2016 – is a fixed-energy end-station providing a very high flux microbeam at the sample position while ID30B, the variable wavelength replacement for ID14-4, provides the possibility to vary the beamsize at the sample position, the possibility (summer 2016) of in situ (i.e. in crystallisation plate) data collection and is the test bed for a new Flex-HCD sample changing robot that will, over the next year or two, replace the SC3 sample changers installed on most end-stations.

A strength of the Structural Biology Group has been its ability to continue to provide world-leading service to our user community while commissioning new facilities. During the UPBL10 project, three of the group’s beamlines, ID23-1, ID23-2 and ID29 have ensured that this has remained the case. Thus, while future editions of ESRF Highlights will surely contain articles based on data collected at the UPBL10 end-stations, this chapter necessarily focuses on some of the extremely interesting results obtained using diffraction data collected at these ‘workhorse’ beamlines. As is always the case, the highlights reported here cover a wide range of structural biology research, published in high-impact journals, including structural studies of membrane proteins (including the giant mitochondrial Complex 1), protein-protein and protein-DNA complexes and other systems that provide significant insights in understanding the molecular basis of diseases or their prevention. In this area, a particular highlight in 2015 is the elucidation, by Rey and colleagues, of the mechanism of action of a series of antibodies (bnAbs) which broadly neutralise the dengue virus. This study reveals that the bnAbs target an ‘Achilles Heel’ of the virus, conserved in all four serotypes and gives hope that a vaccine fully protecting against this disease might be available in the not too distant future.

The insights provided by the articles included here are not always the result of single-crystal X-ray diffraction data collection. Indeed, one of the highlights included here (by Giachin and colleagues) reports the results of an investigation, carried out using extended X-ray absorption fine structure (EXAFS) spectroscopy, of the influence of copper ion coordination in the conversion of the prion protein (PrPC) into a misfolded isoform that causes prion-related diseases including so-called ‘mad cow disease’ in animals and the Creutzfeldt-Jakob disease in humans. This work amply illustrates the increasing use of complementary techniques in structural biology and we predict many more articles illustrating studies carried out using techniques available at beamlines outside the ESRF’s Structural Biology Group portfolio in future editions of ESRF Highlights.

With Phase I of the ESRF Upgrade completed, 2015 also saw the official launch of Phase II of the project, ESRF-EBS, and our thoughts have now firmly turned to how best future generations of structural biologists can exploit the ultra-brilliant X-ray beams that will be produced. Data collection from single cryocooled crystals will clearly remain a staple technique. However, the reduction in the horizontal emittance of the electron beam in the storage ring and the corresponding reduction in X-ray beam size and divergence that the EBS project will bring, will allow the development of a new generation of ESRF MX beamlines with, in some cases, flux densities at the sample position ~5 orders of magnitude higher than is currently the case. Such beamlines, when operated in conjunction with high frame-rate (>1 kHz), continuous readout, detectors will be optimised for multi-crystal data collection techniques both at cryo [4] and room temperatures, synchrotron serial crystallography (SSX, see article by Nogly et al., in this chapter). We also anticipate a revival in time-resolved crystallography studies employing pump-probe methods and predict that, in the future, crystal structure analysis will involved, for a single target, multiple structure determinations. This will enable the conformational landscape of the molecule under study to be better mapped than is currently the case. This information, when combined with data from other techniques [5] including small-angle X-ray scattering, NMR spectroscopy, cryo-electron microscopy and theoretical calculations – all of which are available via the technical platforms of the Partnership for Structural Biology ( – will enable and facilitate studies of the dynamics of biological macromolecules that are crucial to understanding the way in which they function.

We will, as usual, consult the ESRF Structural Biology User Community when planning the best way forward. To this end, following Phase-II-centred sessions at workshops organised at the 2014 (SSX) and 2015 (complementary techniques in Structural Biology), the ESRF User Meeting in 2016 features a micro symposium dedicated to possibilities in (time-resolved) room temperature crystallography.

G. Leonard and  C. Mueller-Dieckmann



[1] C. Mueller-Dieckmann et al., Eur. Phys. J. Plus 130,  70 (2015).
[2] A. Round et al., Acta Cryst. D71, 67-75 (2015).
[3] S. Kharde et al., Nucleic Acids Res. 43, 7083–95 (2015).
[4] U. Zander et al., Acta Cryst. D71, 2328-2343 (2015).
[5] S. Larsen, IUCrJ, 2, 475-476 (2015).