As noted in the introduction to the Structural Biology Chapter in last year’s ESRF Highlights, 2015 marked the end of the UPBL10 project carried out within Phase I of the ESRF Upgrade Programme. Once all four end-stations constructed during UPBL10 had entered full operation, we had hoped that 2016 would be a year of quiet consolidation and evolution of the ESRF facilities for Structural Biology. In fact, 2016 has proved to be an extremely busy year for the group, its beamlines and its user community. Indeed, the financial and human resources released by the completion of UPBL10 meant we could now turn our attention to several major projects that had been either put on hold in recent years or were required to improve the service we offer to our external user community.

The first major development of 2016 was the completion and approval of the Technical Design Report (TDR) for the ID23-2 nanobeam project, which is now underway. ID23-2 was the world’s first microfocus beamline (focal spot ~5 x 7 µm2 at the sample position) dedicated to macromolecular crystallography (MX), producing many important crystal structures, including those of G-protein coupled receptors (GPCRs). The nanobeam project, due for completion in May 2017, will see this focal spot size complemented by a much smaller spot ~1 µm in diameter, providing new opportunities in protein microcrystallography including in the relatively new technique of synchrotron serial crystallography (SSX). The second major project launched in 2016 was a campaign to replace all of the ageing SC3 sample changers with high-capacity FlexHCD devices following initial prototyping of the device on ID30B. The increased capacity and reliability of the FlexHCD – now also installed on ID23-1 and ID29 with ID23-2 and ID30A-3 waiting in the wings – will be a long-awaited benefit to our users that we hope will also result in increased remote access to our beamlines. Nevertheless, please spare a thought for the soon to be discarded SC3s. While they sometimes received a relatively bad press, particularly in recent years, they did revolutionise sample mounting at the ESRF. Indeed, in the 10 years in which they were in operation, they mounted, dismounted (and occasionally dropped!) around 500,000 samples and we probably should remember them more fondly than history might eventually record. The third major project started in 2016 marks a significant new direction for Structural Biology at the ESRF – the purchase of a start-of-the-art cryo-electron microscope. During the coming year (first external users are foreseen for the Autumn of 2017) the microscope will be installed in the Belledone experimental hall extension where it will be operated as a ‘beamline’ and form part of a newly-established Partnership for Structural Biology (PSB) platform for cryo-electron microscopy (cryo-EM). The creation of this PSB platform will provide two major benefits to our user community: operation of the microscope will be supported by staff from the Grenoble-based institutes, the ESRF, the IBS and the EMBL Grenoble Outstation; external ESRF users requiring cryo-EM as a vital component of their projects will eventually also have access to several other microscopes at both the IBS and the EMBL Grenoble Outstation. The conception and planning of this project has been a huge undertaking for the ESRF and its PSB partners and it may not have come to fruition if it were not for the excellent support we received from our external user community. For this, many thanks are due.

Despite the efforts and resources required to ensure the success of the projects referred to above, 2016 did see much of the hoped-for consolidation and evolution of our facilities. Many ‘minor’ improvements to our beamlines included improved omega axis rotation speed (now 720o/second) on ID29; the implementation of faster mesh scans on ID30B; the processing of the 25,000th sample on the completely automatic end-station ID30-A1 and the rolling out of the ID30A-1 workflows to ID30A-3 and ID30B; the full integration of the EIGER 4M detector on ID30A-3 (data collection at 750 Hz frame-rates is now possible);  the continuing refurbishment of the ID29S Cryobench, now also equipped with an MD2M minidiffractometer and SC3 sample changer (at least one will survive!); the provision of storage areas for samples at both cryogenic and ambient (20oC) temperatures; the provision of a new data backup and processing facility.

In 2016, our beamlines have also been scientifically productive and, as in previous years, the highlights reported here cover a wide range of structural biology research, published in high-impact journals. The selection showcases the many strengths of our beamlines in facilitating high quality science that has allowed, amongst a plethora examples not included here, a fuller understanding of the molecular basis of GPCR-based signalling systems, neurotransmission, transcriptional activation in plants, the life-cycle of the influenza polymerase, natural product biosynthetic pathways, the formation of DNA origami switch devices, the synthesis of proteins in eukaryotic cells, protein manufacture, the evolution of DNA polymerases, the synthesis of the universal nicotinamide adenosine dinucleotide cofactor, the inhibition of norovirus by human milk oligosaccharides, the inhibition of potential oncology targets and the control phosphate homeostasis in eukaryotic cells.

2016 has also been a year of looking forward, not just to 2017 but to the long-term future of Structural Biology at the ESRF. Although cryo-EM will play a large part in this future, X-rays will by no means be less relevant, particularly following the ESRF-EBS Upgrade. To ensure that future generations of scientists continue to benefit from the ESRF’s world-leading expertise in providing experimental facilities for MX, we recently proposed plans, in the form of an EBS conceptual design report (CDR 8), for the evolution of ID29 that we hope will culminate in the construction of an ultra-high flux (~1016 photons/sec) microfocus facility for SSX and time-resolved MX. Next year, we hope to be able to report that such a beamline will be part of the long-term future of the ESRF.

Finally, 2016 has seen the closure of BM14 as an MX facility. Lately operated as an ESRF/EMBL/India collaboration, but first opened in 1996, BM14 helped popularise the use of MAD in MX and catalysed the explosion of structural biology as a scientific discipline at the ESRF. The beamline will be missed by many in our field.

G. Leonard and C. Mueller-Dieckmann