Jul 312017
 

Microbeam radiation therapy (MRT) is an innovative preclinical radiotherapy procedure consisting of many micrometre-sized spatially fractionated radiation fields, obtained by collimating a beam of synchrotron radiation with a multi-slit collimator. A typical radiation field of MRT consists of an array of microbeams, each with a width of 50 µm and a centre-to-centre distance of 400 µm.

MRT differs from external beam radiation therapy (EBRT) due to the properties of synchrotron radiation, such as the small angular divergence of the photon beam, the broad spectrum of energies available and the pulsed high-intensity radiation that is produced. The low divergence of the beam ensures that the field does not spread out as it passes through the patient, thus maintaining the spatial fractionation at depth; the high-intensity radiation allows treatment time to be reduced, thus reducing smearing of the microbeam paths in the tissues due to breathing or cardiosynchronous motion.

The most significant advantage of MRT over EBRT is the different radiobiological response of cancerous and healthy tissues to the micrometre-sized MRT field. As the size of the radiation field decreases to the order of micrometres the dose tolerated by normal tissue increases dramatically, whilst maintaining tumour control. This phenomenon, called the dose-volume effect, makes MRT a promising treatment for radioresistant tumours such as osteosarcomas, or tumours located within or near sensitive structures (e.g. glioblastomas in paediatric patients).

Routine dosimetry quality assurance (QA) prior to treatment is necessary to identify any changes in beam condition from the treatment plan, and is undertaken using solid homogeneous phantoms. Solid phantoms are designed for, and routinely used in, megavoltage X-ray beam radiation therapy. These solid phantoms are not necessarily designed to be water-equivalent at low X-ray energies, and therefore may not be suitable for MRT QA.

Cameron et al. (2017). J. Synchrotron Rad. 24, 866-876 simulated dose profiles of various phantom materials and compared them with those calculated in water under the same conditions, so demonstrating quantitatively the most appropriate solid phantom to use in dosimetric MRT QA.

Based on the study, the adoption of virtual water, plastic water DT, RW3 and RM1457 solid water were recommended for MRT QA as water-equivalent solid phantom materials.

 

Jul 252017
 

A pioneering X-ray technique that can analyse artefacts of any shape or texture in a non-destructive way has been developed by an international team of scientists. The method uses X-ray diffraction (XRD) in order to determine crystallographic phase information in artefacts with very high accuracy and without causing damage to the object being scanned [Hansford et al. (2017). Acta Cryst. A73, 293-311].

Using the technique, researchers can identify pigments in paintings and on painted objects – which could potentially be applied in the future to help to clamp down on counterfeit artwork and artefacts and verify authenticity.

The research suggests that the non-invasive technique could also eliminate the frequent need to compromise between archaeological questions that can be solved and the analytical methods available to do so.

Dr Graeme Hansford, from the University of Leicester, explained, “What makes this method really unique is that the shape and texture of the sample become immaterial. I expect future studies to make significant contributions to determining the provenance of a range of archaeological objects, and this data will ultimately provide vital context information for museum collections.

“In paintings, the type of pigment used frequently yields useful insights into methods of production and the organisation of ancient industries, as well as restricting the possible date of manufacture. This could help to determine if the provenance of an artefact is as purported.”

The research was supported by the UK’s Science and Technology Facilities Council.

This news story is an excerpt taken from a press release published by the University of Leicester.

 

Jun 272017
 

Drawing of the Jar

Mechanochemistry is a widespread synthesis technique in all areas of chemistry. Various materials have been synthesized by this technique when the classical wet chemistry route is not satisfactory. Characterization of the reaction mixture is however much less accessible than in solutions.

Recently, in situ observations of mechanochemical reactions have been achieved by X-ray diffraction and Raman spectroscopy. Solid-state reactions can be directly tracked, revealing phase transitions and other material transformations during synthesis in a ball mill jar. This technique has become increasingly popular in different fields of mechanochemistry.

As the X-rays go through the entire jar, the diffraction patterns present a high background due to the scattering from the thick walls of the jar. Also, broad diffraction peaks are expected from the sample as a result of probing a large sample area covering the entire jar. An extra complexity arises from diffraction on the milling balls.

Tumanov et al. [(2017). J. Appl. Cryst. 50. doi:10.1107/S1600576717006744] reasoned that these issues can be resolved by modifying the geometry and material of the milling jar. But, making a jar with a complex geometry using traditional production techniques is complicated, especially at the stage of creating a prototype, when introducing changes into a design should be facile. For this reason they decided to use a 3D printer for the purpose. They show how this useful production tool can quickly make milling jars optimized for improved background, absorption and angular resolution in X-ray powder diffraction experiments; the jars are also more resistant to solvents compared with standard acrylic jars. 3D printing allows for low-cost fast production on demand.

Source files for printing the jars are available as supporting information for the paper.

 

Jun 262017
 

Gorrec F, MRC Laboratory of Molecular Biology, Cambridge, UK

Technology developments, including innovative crystallization screens, are needed to obtain X-ray diffraction-quality crystals from increasingly challenging protein and other macromolecular samples. MORPHEUS crystallization screens are continuously developed to further enhance initial screening. MORPHEUS screens integrate small molecules frequently observed in the PDB to co-crystallize with proteins. These molecules are included to function as additives that act as protein stabilizers, crystal packing bridges, or any other role beneficial to protein crystallization.

Each MORPHEUS screen integrates 96 conditions, a minimal format for limiting amounts of sample. To limit the number of conditions employed, the potential ligands found in the PDB are combined into mixes. Other mixes of compounds are used, such as buffer systems and precipitant mixes that also act as convenient and effective cryoprotectants. The different types of compound mixes are combined using a fixed ratio to generate 3-D grid screens. The preparation of a screen and the optimization of conditions are amenable to automation.

A multitude of test crystallization screens are used against novel and challenging samples produced at the LMB before making choices about the formulation. The main goal is to produce exclusive crystallization hits that were not observed in other screens. MORPHEUS screens, I and II, are now used routinely in many laboratories, while MORPHEUS III is being developed. Before describing the developments related to the MORPHEUS screens, I will briefly present theoretical and pragmatic aspects of macromolecular crystallography that were taken into consideration during the early stages of MORPHEUS development. In the last section I will show how to optimize conditions following the 4-corner method.

A recording of this webinar is now available to view: https://www.youtube.com/watch?v=Gpb4SypWnQY

A complementary event is also available: https://www.youtube.com/watch?v=8cH0YNmDshY

Questions and answers raised during the webinar Formulation of the MORPHEUS protein crystallization screens

If you have any questions about the event please do not hesitate to contact Dr Jonathan Agbenyega, Business Development Manager, IUCr at ja@iucr.org

 

 

May 252017
 

The calculated intensities as Ω and X are varied for a detector at 2θ = 60° (a) and 2θ = 110° (b) for 10 µm crystallites

Are we blindly accepting all the interpretations that arise from our present description of X-ray diffraction?  Is it reasonable that all crystals have to be “ideally imperfect” to determine their structure?  Bragg’s law cannot avoid dynamical effects, and therefore the measured intensity is not equal to the square of the structure factor unless the crystal is assumed to be “ideally imperfect”.  If polycrystalline diffraction is formed from crystals satisfying Bragg’s law, why is the background so high compared with single crystal profiles?  Are more crystals required in polycrystalline diffraction to study complex structures with large unit cells to ensure all the peaks are captured?  If the variation of intensity around the diffraction rings from polycrystalline samples is associated with a large range of crystal sizes, why does the data from a standard reference material of similar size crystals still reveal this variation?  Are we not just modifying our sample description and instrument performance so that the current theory fits the data?  After many years of theoretical and experimental work I am convinced that I have a good explanation.

Let us look back more than a hundred years, when the two Braggs interpreted the experiments of Friedrich, Knipping and Laue.  Their interpretation was simple, clever and explained the data giving us Bragg’s law and the Bragg equation.  This equation gives the position of the diffraction peaks and any surrounding scattering is considered as a perturbation, giving information on the crystal size, strain and defects.  This description struggles to answer the questions above.

Suppose Bragg’s law is not necessary to form a diffraction peak as proposed by Fewster[1], then we can start to answer these questions.  This proposal describes how the specular (mirror) reflections from crystals planes and their periodicity give rise to two peaks, one at the mirror angle and the other at twice the Bragg angle, 2θB.  The mirror peak broadens with crystal defects and distortions, with the whole width scattering intensity towards the angle 2θB.  This broadened mirror peak contributes to the background[2].  The intensity from crystals not satisfying Bragg’s law will form a weak contribution at the angle 2θB, explaining the intensity variation in diffraction rings from polycrystalline samples.  Bragg’s law occurs where the mirror reflection and the angle 2θB peak overlap.  Therefore, if the former is broad as in an imperfect crystal Bragg’s law and therefore the dynamical effects can only exist over a small proportion of the intensity profile.

If Bragg’s law is not a requirement to create a diffraction peak, then it is possible for many peaks to be observed simultaneously.  This explains the diffraction patterns observed at X-ray free electron lasers, i.e. the appearance of several diffraction spots and their variable intensity.  Similarly, the diffraction profiles from polycrystalline materials can be explained, i.e. small numbers of crystals and the full set of peaks from a complex sample.  This description accounts for the data but indicates that a typical measurement of intensity close to a diffraction peak is inadequate, because this is only a proportion of the total intensity, and therefore cannot be directly related to the structure factor.  A study[1] on a polycrystalline silicon sample suggests that this new description gives the structural parameters within acceptable bounds whereas the conventional theory does not.

The significant step in this description is that the intensity is enhanced at the angle 2θB regardless of the crystal orientation.  This can be observed experimentally.  So why has it not been knowingly observed before?  If conventional theory is so strongly part of the crystallographer’s thinking this enhancement is easy to overlook as just some artifact.  This proposal suggests that the derived sample models could be faulty.  The magnitude of this error is difficult to assess, but with three components; the diffraction data, a theoretical description and a model of the structure, we require two of these to be correct to reproduce the third.  Suppose we assume our data is reliable, then if the theory is incomplete the structural model will be biased or unreliable.

I strongly believe that we should be questioning and discussing our current theory of X-ray diffraction, because all our structural models determined to date might be faulty or inaccurate.

[1] Fewster.  (2014).  Acta Cryst. A70, 257-282; doi:10.1107/S205327331400117X

[2] Fewster.  (2016).  Acta Cryst. A72, 50-54; doi:10.1107/S2053273315018975

View the on-demand version of our webinar with Paul Fewster the author of this work on the IUCr YouTube channel.

You can view the questions and answers covered during the webinar here.

 

May 192017
 

An example of a three-dimensional structure of a macromolecule solved using cryo-electron microscopy

The invention of the electron microscope revolutionized how scientists view small structural details. The technology has undergone considerable evolution and in recent years single-particle cryo-electron microscopy (cryo-EM) has gained importance in structural biology. A topical review on cryo-EM has recently been published in Acta Crystallographica Section F (Vénien-Bryan et al., 2017, Acta Cryst. F73, 174-183). The review discusses the importance of cryo-EM and highlights recent developments. It describes how cryo-EM and other structural biology techniques, especially X-ray crystallography, now complement each other and how cryo-EM has been used in drug discovery.

The synergistic convergence of technological and computational advances now makes cryo-EM a feasible method for determining structures at near-atomic to atomic resolution (~5-2 Å). The latest generation of cryo-electron microscopes are equipped with direct electron detectors and software for the automated collection of images. In combination with the use of advanced image-analysis methods, the performance of this technique has dramatically improved. Less than a decade ago calculating a sub-10 Å resolution structure was an accomplishment but it is now common to generate structures at sub-5 Å resolution and even better. It is becoming possible to obtain high-resolution structures of biological molecules relatively quickly, in particular large ones (>500 kDa) which, in some cases, have resisted more conventional methods such as X-ray crystallography or nuclear magnetic resonance (NMR).

The potential impact of cryo-EM on drug discovery is large. Newly resolved protein structures may provide details of the precise mechanisms that are essential for cellular physiological processes. The ability to attain atomic resolution may support the development of new drugs that target these proteins, allowing medicinal chemists to understand the relationship between their molecules and targets. In addition, recent developments in cryo-EM combined with image analysis can provide unique information on connections between conformational variability and the function of macromolecular complexes.

The authors conclude that although crystallography remains the method of choice to obtain structural information from proteins for use in drug discovery, the arsenal of methods now available increases the range of possibilities, and cryo-EM is one of these methodologies, particularly for investigating changes in conformation. However, what still remains to be improved is the provision of high-quality proteins for study and so developments in purification processes are becoming fashionable once again.

 

May 032017
 

C. Richard A. Catlow, Main Editor, IUCrJ

The papers published during the last year in IUCrJ in the fields of materials and computational science illustrate well the challenges posed by structural problems in the science of materials and the key role that computation can play in this and related fields in structural science. As in previous years, they demonstrate the continuing developments in techniques and instrumentation and the increasingly complex structural problems which these developments now make accessible; the role of computation in interpreting and predicting structures is equally clear.

An excellent example of technical developments facilitating new structural science is provided by the article of [Meng, Y. & Zuo, J.-M. (2016). IUCrJ, 3, 300-308], which probes three-dimensional nano-structures using a technique that employs high-resolution and low-dose scanning electron nano-diffraction (SEND) to acquire three-dimensional diffraction patterns. Their work investigates TiN – a material that is widely used in the electronics industry – and Fig. 1 illustrates how they were able to reconstruct grain structures within the material. Detailed knowledge of this microstructure is essential in understanding and optimizing the properties of the material.

Figure 1. Reconstructed grains and their orientations. Meng, Y. & Zuo, J.-M. (2016). IUCrJ, 3, 300-308

Previous editorials have emphasized the key role of diffuse scattering, which is also facilitated by technical advances. The importance of the field in materials science is well illustrated by the article of [Sawa, H. (2016). IUCrJ, 3, 298-299], which highlights the work of [Welberry, T. R. & Goossens, D. J. (2016). IUCrJ, 3, 309-318] on the interpretation of diffuse scattering from the high-temperature superconductor, HgBa2CuO4 + δ. Analysis of the diffuse scattering data reveals fascinating features involving the displacement of metal atoms around oxygen interstitial chains. This article along with several others demonstrates the need to elucidate complex structural features in disordered materials.

Analysis of diffuse scattering is also vital in the particularly exciting challenge of developing detailed models for the atomic arrangements in quasicrystals. The article of [Ishimasa, T. (2016). IUCrJ, 3, 230-231] highlights the study of [Yamada, T., Takakura, H., Euchner, H., Pay Gómez, C., Bosak, A., Fertey, P. & de Boissieu, M. (2016). IUCrJ, 3, 247-258] on the atomic structure and phason modes of the Sc–Zn icosahedral quasicrystal, which employs synchrotron-based diffraction and diffuse scattering to investigate this difficult problem.

Figure 2. A polyhedral representation of the denisovite structure. Rozhdestvenskaya, I. V., Mugnaioli, E., Schowalter, M., Schmidt, M. U., Czank, M., Depmeier, W. & Rosenauer, A. (2017). IUCrJ, 4, XXX-XXX.

The complexity of structural problem that can now be addressed is well illustrated in the paper of [Rozhdestvenskaya, I. V., Mugnaioli, E., Schowalter, M., Schmidt, M. U., Czank, M., Depmeier, W. & Rosenauer, A. (2017). IUCrJ, 4, XXX-XXX], who use a wide range of techniques including several electron crystallographic methods, XRPD and modelling to solve the structure of denisovite, a highly complex, fibrous, polytypical silicate. The structure revealed is shown in Fig. 2. The article is an elegant illustration of the capacity of, and the need for, a multi-technique approach in addressing structural problems in materials science.

A further example of complex structural science is given by the study of SnTe reported by [Sist, M., Jensen Hedegaard, E. M., Christensen, S., Bindzus, N., Fischer, K. F. F., Kasai, H., Sugimoto, K. & Brummerstedt Iversen, B. (2016). IUCrJ, 3, 377-388]. This material is increasingly investigated owing to its potential as a thermoelectric material and as a topological insulator. Their study again reveals the importance of disorder and emphasizes the need to include the effects of disorder in any theoretical investigation of the material.

Several papers illustrate both the growing power of computational methods in structural science and the role of new methodologies and algorithms in investigating structural problems [Genoni, A., Dos Santos, L. H. R., Meyer, B. & Macchi, P. (2017). IUCrJ, 4, 136-146] explore the concept of X-ray-constrained Hartree–Fock wavefunctions (XC–WF) and discuss how the procedure can be used to extract correlation effects. Their careful analysis demonstrates that the single determinant XC–WF only partially captures the effects of correlation. The paper of [Wall, M. E. (2016). IUCrJ, 3, 237-246] on quantum crystallography and the charge density of urea shows, as the authors comment, the benefits and feasibility of integrating fully periodic quantum charge-density calculations into ultra-high-resolution X-ray crystallographic model building and refinement. While the value of force-field-based methods is illustrated by the paper of [Li, X., Neumann, M. A. & van de Streek, J. (2017). IUCrJ, 4, 175-184], who evaluate different force fields in the context of their use in dynamical simulations for the prediction of chemical shifts in solid-state NMR.

The importance of the structural science of materials is, of course, illustrated by many other articles published in other journals. Of particular interest is the way in which multi-technique approaches are pinning down key structural features of catalytic materials under real operating conditions. We have previously highlighted the work of [Lezcano-Gonzalez, I., Oord, R., Rovezzi, M., Glatzel, P., Botchway, S. W., Weckhuysen, B. M. & Beale A. M. (2016) Angew. Chem. Int. Ed., 55, 5215-5219], which combines high-resolution fluorescence-detection X-ray absorption near-edge spectroscopy, X-ray diffraction and X-ray emission spectroscopy under operando conditions to provide detailed new insights into the nature of the Mo species on zeolite ZSM-5 during methane de­hydro­aromatization. Another recent example is the work of [Malta, G., Kondrat, S. A., Freakley, S. J., Davies, C. J., Lu, L., Dawson, S., Thetford, A., Gibson, E. K., Morgan, D. J., Jones, W., Wells, P. P., Johnston, P., Catlow, C. R. A., Kiely, C. J. & Hutchings, G. J. (2017). Science, 355, 1399-1403], who combined XAFS and modelling to show that in an industrially important acetyl­ene hydro­chlorination catalyst, comprising gold on a carbon support, the active sites are not, as previously thought, gold nano-clusters but single gold ions. Catalysis will unquestionably continue to pose fascinating problems for structural science.

It is hoped that this brief survey gives an impression of the range and excitement of the field of the contemporary structural science of materials and the way in which this can be unravelled by a multi-technique approach using experiment and computation. IUCrJ continues to welcome submissions in this growing field.

 

 

Apr 202017
 

Detail of the coordination spheres of the bromide anion with Et3BuN+Br−

While an IUPAC definition of hydrogen bonding was only released in 2011 after decades of discussions in the scientific community, it did not take such a long time to come up with an analogous definition of halogen bonding, following a revival of this interaction in the literature which can be traced back to the early 1990s, Fourmigué, M. (2017). Acta Cryst. B73, 138-139

The halogen-bonding interaction is essentially described as an electrostatic interaction between a charge concentration (Lewis base) and a charge-depleted area, called an σ-hole, that a covalently bound halogen atom exhibits in the extension of this bond.

In a recent paper by Szell et al, (2017). Acta Cryst. B73, 153-162 single-crystal X-ray diffraction structures have been reported for a series of seven halogen-bonded co-crystals featuring 1,3,5-tris(iodoethynyl)-2,4,6-trifluorobenzene as the halogen-bond donor, and bromide ions (as ammonium or phosphonium salts) as the halogen-bond acceptors. Depending on the stoichiometry, the resulting frameworks can form honeycomb structures of variable geometry, but also systems with four or six halogen bonds to the bromide ion. While the counter-cations generally occupy the void spaces in the present work, the construction of halogen-bonded frameworks with potential gas storage applications is an appealing prospect which may be facilitated in the future by ligands enabling directional and multidentate interactions.

 

Mar 302017
 

The large-solid-angle X-ray Raman scattering spectrometer at ID20. Photo credit: ESRF/McBride

S. Huotari and co-workers [J. Synchrotron. Rad. (2017), 24, 521-530] describe an end-station for X-ray Raman spectroscopy at beamline ID20 of the European Synchrotron Radiation Facility. The end-station is dedicated to the study of shallow core electronic excitations using non-resonant inelastic X-ray scattering.
X-ray Raman scattering (XRS) spectroscopy is a versatile tool for studying shallow X-ray absorption edges using hard X-rays. It has proven to be an invaluable technique for the study of electronic excitations in a variety of sample systems such as crystals, liquids and gases. Over the past decades, XRS has been applied to solve geoscientific questions by studying shallow core edges under extreme pressure and temperature conditions, follow chemical reactions in situ, and study liquid samples under well defined thermodynamic conditions.
A drawback of XRS is the orders-of-magnitude weaker scattering cross section in comparison with the probability for photoelectric absorption. This can be compensated for by using light sources with a very high brilliance and efficient signal collection; this has been the guiding motive for the design of the spectrometer presented in this paper.
The new end-station provides an unprecedented instrument for X-ray Raman scattering, and will open the door to renewed studies of low-energy X-ray absorption spectra in materials under in situ conditions, such as operando batteries and fuel cells, in situ catalytic reactions, and extreme pressure and temperature conditions.

Mar 282017
 

Dr Rosemary Wilson @rawilson80 Scientific training and outreach officer, EMBL Hamburg

Long after the lights went on in the PETRA III Max von Laue experimental hall on the DESY campus, and the 14 beamlines became hives of activity, one corner has remained dark and seemingly forgotten. But there have always been plans for this corner of the Max von Laue Hall, and now those plans are taking shape. This hutch, situated directly behind the EMBL crystallography beamline P14, will house P14.EH2, a new experimental endstation which will cater for time-resolved crystallography experiments. In the autumn of 2016, EMBL group leader Thomas Schneider and Professor Arwen Pearson from the Centre of Ultrafast Imaging (CUI) at the University of Hamburg, were successful in securing a grant from the German federal government which in part provides funds for designing and building the endstation. Since then basic designs for the instruments have been decided, the first bits of equipment ordered and positions advertised for postdocs to help construct and run the endstation. The group hope to be able to welcome friendly users by the end of 2018. So how about some details?

Why a new endstation?

PETRA III produces some of the most brilliant and intense X-rays on the planet. The EMBL macromolecular crystallography beamline P14 is optimised to create a tight and parallel beam. With so many photons reaching the sample at the same time, scientists can start to watch the structural changes a protein goes through during a reaction, rather than a time-averaged snapshot as we are familiar with in traditional crystallography. Schneider, Pearson and their teams have already used P14 to do these types of time resolved crystallography experiments, but the set-up is not ideal in the long run.

Briony Yorke in the hutch that will house the new endstation. The X-ray beam will enter the hutch through the hatch in the back wall. Photo: Rosemary Wilson

The hutch for P14.EH2 sits directly behind P14 and the new endstation will be fed by the same X-ray beam. Each time-resolved experiment will need a different instrumental set-up, optimised to the type of results the scientists want to achieve. Having a separate hutch dedicated to the complicated time-resolved set-ups means that the regular operation on P14 doesn’t need to be interrupted and the scientists can take time to plan, design and build their set-up before pressing the button to allow the X-ray beam into the hutch. “The idea is that the set-up will be very flexible and modular” explains Wellcome Postdoctoral Fellow Briony Yorke (@BrionyYorke), who is working with Pearson on the endstation. Due to the tight angle that the X-ray beam leaves the PETRA III storage ring, the other beamline hutches and endstations are narrow, with access to equipment only possible by climbing over and under beamlines and detectors. The nature of the time-resolved experimental set-up means that access has to be easy and comfortable, and this was a major consideration during the design process. (See the project webpage http://www.embl-hamburg.de/services/mx/P14_EH2 for more details on the hutch layout design and specifications.)

What methods and hardware will be available?

Time-resolved crystallography works by taking a series of snapshots of a molecule such as a protein in quick succession to build up a movie of the protein’s structural changes during a reaction (see also: Taking crystallography to the fourth dimension). In practical terms, the X-ray beam has to be interrupted to create many successive images. “The trick is to turn the X-ray beam on and off faster than the process we are interested in” explains Briony. “The current shutter on P14 is a milli-second shutter, so the only possibility to look at shorter time slices is to get the detector to count for a shorter time period by repeatedly turning it on and off, since we physically cannot open and shut the shutter fast enough.” On the new endstation, a circular metal disc with pattern of holes stamped in it called a chopper will repeatedly ‘chop’ the X-ray beam, breaking up the signal to provide the sought after shorter time slices.

The prototype Hadamard chopper designed by Briony’s master student Anke Puckert and made on the DESY site. Of the three outer ring sequences, the central pattern encodes the Hadamard sequence, the other two are control patterns. Credit: Anke Puckert

Briony’s particular interest is Hadamard time-resolved crystallography, a method she developed during her PhD, which will be an available option in the new set-up. While a chopper for standard time-resolved crystallography experiments may have a single hole in it, creating an interruption every, say second as it rotates through the beam, Hadamard choppers require a much more intricate pattern of holes. This will create many more interruptions, resulting in more data per crystal, and a more detailed ‘movie’ of the protein dynamics.

“The choppers pose quite a challenge” says Briony. “During experiments they will be spinning at very high speeds (several 1000 rpm), so they have to be cooled with water and placed under a vacuum, and shielded in a bullet-proof case something goes wrong!” Another key bit of equipment that will be found in the new hutch will be a laser for initiation of the (bio)chemical process the experiment aims to study. “The laser impulse will be delivered with fibre optics” explains Briony. “This will enable a really precise initiation of the experiments” she adds.

What science will it be used for?

“We are interested in looking at structural changes within proteins that happen during a chemical reaction, for example in an enzyme. The rate determining steps of these reactions happen on the microsecond to millisecond time-scale which P14.EH2 is designed to handle. We want to provide a regular service for people interested in exploring protein dynamics” says Briony. She will be using the time-resolved crystallography endstation, for example, to investigate how cataracts form in our eyes. “Cataracts form when proteins in our eyes start to stick together. But we don’t know what triggers this process. If we can get a picture of how and why this happens, we might be able to design medication to prevent them forming or even reverse the process” she says. P14.EH2 is likely to be interesting for a whole range of applications – from biotechnology to medicine. “For example, we could use the endstation to understand how some bacteria make crude oil, or eat plastic” explains Briony, “or gain a better understanding of how enzymes interact with medicines in our bodies. And all this evidence can be used to help build better computer simulations of molecular motions” she concludes.

What’s next?

Any day now the first instruments should arrive and the instrumentation group at EMBL can start constructing the endstation. Visit the project webpage for regular updates on their progress!

You can see papers published by Dr Thomas R. Schneider in IUCr Journals here

You can see papers published by Professor Arwen R. Pearson in IUCr Journals here