Electron Bio-Imaging Centre (eBIC): the UK national research facility for biological electron microscopy

Abstract

The recent resolution revolution in cryo-EM has led to a massive increase in demand for both time on high-end cryo-electron microscopes and access to cryoelectron microscopy expertise. In anticipation of this demand, eBIC was set up at Diamond Light Source in collaboration with Birkbeck College London and the University of Oxford, and funded by the Wellcome Trust, the UK Medical Research Council (MRC) and the Biotechnology and Biological Sciences Research Council (BBSRC) to provide access to high-end equipment through peer review. eBIC is currently in its start-up phase and began by offering time on a single FEI Titan Krios microscope equipped with the latest generation of direct electron detectors from two manufacturers. Here, the current status and modes of access for potential users of eBIC are outlined. In the first year of operation, 222 d of microscope time were delivered to external research groups, with 95 visits in total, of which 53 were from unique groups. The data collected have generated multiple high-to intermediate-resolution structures (2.8-8 Å ), ten of which have been published. A second Krios microscope is now in operation, with two more due to come online in 2017. In the next phase of growth of eBIC, in addition to more microscope time, new data-collection strategies and sample-preparation techniques will be made available to external user groups. Finally, all raw data are archived, and a metadata catalogue and automated pipelines for data analysis are being developed.

Estimation of high-order aberrations and anisotropic magnification from cryo-EM data sets in RELION-3.1

“…Titan Krios microscopes come equipped with lenses that can be tuned to correct for threefold astigmatism, although this operation is typically only performed by engineers. The Titan Krios microscope that was used to image the tau filaments from the American football player is part of the UK national cryo-EM facility at Diamond (Clare et al, 2017). After measuring the severity of the aberrations, its lenses were re-adjusted, and no higher-order aberrations have been detected on it since (Peijun Zhang, personal communication).…”

Machine learning and big scientific data

“…Figure 2 shows a schematic of the cryoEM data processing pipeline [25]. Investment in infrastructure, such as the eBIC facility on the Harwell campus [26] and CCP-EM [27], is supporting a rapid expansion in the use of cryoEM in structural studies. Structure determination involves a sequence of steps, each of which could benefit from algorithmic and computational improvements.…”

Where is crystallography going?

“…In particular, we expect the same trajectory of automated workflows that have revolutionized MX to increasingly impact electron microscopy, and the proper handling and preservation of metadata, pioneered in ISPyB, which is already being integrated with EM software analysis (la Rosa-Trevín et al, 2016). In the medium term we can expect a rash of EM centres to spring up at synchrotrons, following the eBIC model established at Diamond, which currently houses four high-end machines (Stuart et al, 2016;Clare et al, 2017;Saibil et al, 2015), and we might expect the number of high-end machines at such centres to be comparable to the number of MX beamlines that they sit alongside, to provide a comparable service to the community (Stuart et al, 2016).…”