UK set to be global leader in providing large-scale industrial access to Cryo-EM for drug discovery thanks to new collaboration.
Thermo Fisher Scientific and Diamond Light Source are creating a step change for life sciences sector, a one-stop shop for structural biology and one of largest cryo-EM sites in the world.
An agreement to launch a new cryo-EM capability for use in the life sciences industry sector by Thermo Fisher Scientific, one of the world leaders in high-end scientific instrumentation, and Diamond Light Source, the UK’s national synchrotron and one of the most advanced scientific facilities in the world, was announced today ahead of the official opening of the new national electron bio-imaging centre (eBIC) which will be held at Diamond on September 12th 2018.
This announcement confirms Diamond as one of the major global cryo-EM sites embedded with an abundance of complementary synchrotron-based techniques, and thereby, provides the life sciences sector with an offer not available anywhere else in the world.
Professor Dave Stuart, Life Sciences Director at Diamond and MRC Professor of Structural Biology at the University of Oxford, Department of Clinical Medicine, says, “Access to 21st century scientific tools to push the boundaries of scientific research is essential for both academia and industry, and what we have created here at Diamond is truly unique in the world in terms of size and scale. The new centre offers the opportunity for almost real-time physiology, capturing proteins in action at cryo-temperatures by flash-freezing them at various stages. What Diamond has created with eBIC is an integrated facility for structural biology, which will accelerate R&D for both industry and academic users. The additional advanced instruments made available by Thermo Fisher will position the UK as a global leader in providing large-scale industrial access to cryo-EM for drug discovery research. Our new collaboration provides a step change in our offer for industry users and helps ensure that R&D remains in the UK.”
Image: Close up sample loading Krios I.
Researchers have explored the phase diagram of zinc under high pressure and high temperature conditions, finding evidence of a change in its structural behaviour at 10 GPa. Experiments profited from the brightness of synchrotron light at ALBA and Diamond.
The field of materials science studies the properties and processes of solids to understand and discover their performances. Synchrotron light techniques permit to analyse these materials at extreme conditions (high pressure and high temperature), getting new details and a deep knowledge of them.
Studying the melting behaviours of terrestrial elements and materials at extreme conditions, researchers can understand the phenomena taking place inside them. This information is of great value for discovering how these materials react in the inner core of Earth but also for other industrial applications. Zinc is one of the most abundant elements in Earth’s crust and is used in multiple areas such as construction, ship-building or automobile.
Figure: P-T phase diagram of zinc for P<16 GPa and T<1600K. Square data points correspond to the X-ray diffraction measurements. Solid squares are used for the low pressure hexagonal phase (hcp) and empty symbols for the high pressure hexagonal phase (hcp’). White, red and black circles are melting points from previous studies reported in the literature. The triangles are melting points obtained in the present laser-heating measurements. In the onset of the figure is shown the custom-built vacuum vessel for resistively-heated membrane-type DAC used in the experiments at the ALBA Synchrotron.
Investigations at Diamond may lead to easier ways to synthesise nanoparticle supercrystals
Self-assembly and crystallisation of nanoparticles (NPs) is generally a complex process, based on the evaporation or precipitation of NP-building blocks. Obtaining high-quality supercrystals is slow, dependent on forming and maintaining homogenous crystallisation conditions. Recent studies have used applied pressure as a homogeneous method to induce various structural transformations and phase transitions in pre-ordered nanoparticle assemblies. Now, in work recently published in the Journal of Physical Chemistry Letters, a team of German researchers studying solutions of gold nanoparticles coated with poly(ethylene glycol)- (PEG-) based ligands has discovered that supercrystals can be induced to form rapidly within the whole suspension.
Figure: 2D SAXS patterns of PEG-coated gold nanoparticles (AuNP) with 2 M CsCl added at different pressures. Left: 1 bar; Middle: 4000 bar; Right: After pressure release at 1 bar. The scheme on top illustrates the structural assembly of the coated AuNPs at different pressures: At 1 bar, the particle ensemble is in an amorphous, liquid state. Upon reaching the crystallization pressure, face-centred cubic crystallites are formed by the AuNPs. After pressure release, the AuNPs return to the liquid state.
Magnetic vortices observed in antiferromagnetic haematite were transferred into ferromagnetic cobalt.
Vortices are common in nature, but their formation can be hampered by long range forces. In work recently published in Nature Materials, an international team of researchers has used mapped X-ray magnetic linear and circular dichroism photoemission electron microscopy to observe magnetic vortices in thin films of antiferromagnetic haematite, and their transfer to an overlaying ferromagnetic sample. Their results suggest that the ferromagnetic vortices may be merons, and indicate that vortex/meron pairs can be manipulated by the application of an in-plane magnetic field, giving rise to large-scale vortex–antivortex annihilation. Ferromagnetic merons can be thought of as topologically protected spin ‘bits’, and could potentially be used for information storage in meron racetrack memory devices, similar to the skyrmion racetrack memory devices currently being considered.
Image: Graphic outlining the antiferromagnetic rust vortices. The grayscale base layer represents the (locally collinear) magnetic order in the rust layer, and the coloured arrows the magnetic order imprinted into the adjacent Co layer.
A team of researchers from the University of Cambridge, Diamond Light Source and Argonne National Laboratory in the US have demonstrated a new approach that could fast-track the development of lithium-ion batteries that are both high-powered and fast-charging.
In a bid to tackle rising air pollution, the UK government has banned the sale of new diesel and petrol vehicles from 2040, and the race is on to develop high performance batteries for electric vehicles that can be charged in minutes, not hours. The rechargeable battery technology of choice is currently lithium-ion (Li-ion), and the power output and recharging time of Li-ion batteries are dependent on how ions and electrons move between the battery electrodes and electrolyte. In particular, the Li-ion diffusion rate provides a fundamental limitation to the rate at which a battery can be charged and discharged.
British researchers from the University of York and the University of Oxford have shown the mechanism that leads to body odour in armpits by studying the molecular process at the ESRF and other lightsources.
Stepping into a cramped bus on a hot summer day can sometimes translate into having to hold your breath and a very unpleasant experience. Sweat production increases in hot weather, and, with it, body odour. Despite much research and antiperspirant deodorants, scientists still haven’t managed to selectively block body odour.
Researchers from the University of York and the University of Oxford have recently used the ESRF and Diamond Lightsource to find out what happens at a molecular level when we smell badly. They focused on the apocrine gland, which is found only in the armpit, genitalia and ear canal. It secrets an odourless lipid-rich viscous secretion, which is likely to play a role in scent generation, but it is not involved in thermoregulation.
It all comes down to bacteria. “The skin of our underarms provides a unique niche for bacteria,” explains investigator Gavin Thomas, professor in the department of biology at the University of York and co-leader of the study. “Through the secretions of various glands that open onto the skin or into hair follicles, this environment is nutrient-rich and hosts its own microbial community, the armpit microbiome, of many species of different microbes.”
Image: Picture showing how body odour is produced in armpits.
Credit: University of York and Oxford.
There’s nothing quite like an ice cream on a hot day, and eating it before it melts too much is part of the fun.
Ice cream is a soft solid, and its appeal is a complex combination of ‘mouthfeel’, taste and appearance, which are all strongly affected by the underlying microstructure. We know that changes in the microstructure of ice cream occur at storage temperatures above -30°C, so they will occur during shipping, and in freezers at the supermarket and at home. In their ongoing quest to create the perfect ice cream, an international team of researchers brought samples to Diamond to investigate the temperature dependence of these microstructural changes, and the underlying physical mechanisms that control microstructural stability.
At Diamond Light Source we have built and developed a state-of-the art optical metrology laboratory which is equipped with instruments to test and inspect extremely precise mirrors used to focus X-rays for Diamond’s beamlines.
To calibrate this measuring equipment we needed a device that can produce very tiny angle changes in a precise and controlled way.
Now, instead of a 1m spirit level, we use a 1000km long spirit level, with a 1mm spacer under one end. This would create an angular change of 1 nanoradian, which is exactly what Diamond’s Nano-angle generator (NANGO) can accuractely create.
Kiishi and Hannah have spent five days within the Diamond Communications team as part of their work experience week. They’ve shared their experience, with a special focus on engineering, in this article.
2018 is the Year of Engineering. A national campaign to celebrate the world and wonder of engineering and increase awareness and understanding of what engineers do among young people. Engineering is a vital part of everyday life, from coffee machines and smartphones, to Mars rovers and artificial intelligence.
Some ways in which Diamond encourages young people to get into engineering include through open days; the facility hosts five every year as well as workshops for prospective students who are interested in the field of science and engineering. Recently Diamond ran Project M which involved collecting 1000 samples of calcium carbonate from 100 schools across the country. These samples were analysed by Diamond and the results were sent back to the schools to process. They were interested in finding out how different additives affect the forms of calcium carbonate produced. This project was the first ‘citizen science’ project at Diamond and allowed schools to really get involved in a genuine scientific experiment. This is just one example of how Diamond is very much community based and strives to involve local residents and really get people excited about engineering.
Using synchrotron light, researchers from CIC bioGUNE have solved the structure of RavN, a protein that Legionella pneumophila uses for stealing functions and resources of the host cell.
Mimicry is the ability of some animals to resemble others in their environment to ensure their survival. A classic example is the stick bug whose shape and colour make him unnoticed to possible predators. Many intracellular pathogens also use molecular mimicry to ensure their survival. A part of a protein of the pathogen resembles another protein totally different from the host and many intracellular microorganisms use this capability to interfere in cellular processes that enable their survival and replication.
The Membrane Trafficking laboratory of the CIC bioGUNE in the Basque Country, led by Aitor Hierro, in collaboration with other groups from the National Institutes of Health in the United States, have been working for several years in understanding how the infectious bacterium Legionella pneumhopila interacts with human cells. During this research, experiments have been carried out at the XALOC beamline of the ALBA Synchrotron and I04 beamline of Diamond Light Source (UK). The results enabled scientists to solve the structure of RavN, a protein of L. pneumophila that uses this molecular mimicry to trick the infected cell.
Figure: (extract) Schematic representation of the structure of RavN1-123 as ribbon diagram displayed in two orientations (rotated by 90° along the x axis). Secondary elements are indicated as spirals (helices) or arrows (beta strands), with the RING/U-box motif colored in orange and the C-terminal structure colored in slate. (Full image here)
A paper in PNAS by an international scientific collaboration from the UK, Germany and Switzerland is the 7000th to be published as a result of innovative research conducted at Diamond Light Source, the UK’s Synchrotron.
This new paper reveals details of the 3D spin structure of magnetic skyrmions, and will be of key importance for storing digital information in the development of next-generation devices based on spintronics.
Laurent Chapon, Diamond’s Physical Sciences Director, explains the significance of these new findings: “A skyrmion is similar to a nanoscale magnetic vortex, made from twisted magnetic spins, but with a non-trivial topology that is ‘protecting them’. They are therefore stable, able to move, deform and interact with their environment without breaking up, which makes them very promising candidates for digital information storage in next-generation devices. For years, scientists have been trying to understand the underlying physical mechanisms that stabilise magnetic skyrmions, usually treating them as 2D objects. However, with its unique facilities and ultra-bright light, Diamond has provided researchers the tools to study skyrmions in 3D revealing significant new data.”
As spintronic devices rely on effects that occur in the surface layers of materials, the team was investigating the influence of surfaces on the twisted spin structure. It is commonly assumed that surface effects only modify the properties of stable materials within the top few atomic layers, and investigating 3D magnetic structures is a challenging task. However, using the powerful circularly polarised light produced at Diamond, the researchers were able to use resonant elastic X-ray scattering (REXS) to reconstruct the full 3D spin structure of a skyrmion below the surface of Cu2OSeO3.
Image: (extract) Illustration of a ‘Skyrmion tornado’. The skyrmion order changes from Néel-type at the surface to Bloch-type deeper in the sample. On the right hand side, the corresponding stereographic projections of these two boundary skyrmion patterns are shown. Full image and detailed article here.
Gaining fundamental insights into the full dielectric behaviour of MOFs across the infrared and THz.
An international team of researchers from Oxford, Diamond, and Turin, has demonstrated the novel use of synchrotron radiation infrared (SRIR) reflectivity experiments, to measure the complex and broadband dielectric properties of metal-organic framework (MOFs) materials. Open framework compounds like MOFs have the potential to revolutionise the field of low-k dielectrics, because of their tuneable porosity coupled with an enormous combination of physicochemical properties not found in conventional systems. Furthermore, next generation IR optical sensors and high-speed terahertz (THz) communication technologies will stand to benefit from an improved understanding of the fundamental structure-property relations underpinning novel THz dielectric materials.
Image: (extract) The high-resolution reflectivity data obtained were subsequently used to determine the real and imaginary components of the complex dielectric function by adopting the Kramers−Kronig Transformation theory.
X-ray fluorescence mapping to measure tumour penetration by a novel anticancer agent.
A new anticancer agent developed by the University of Warwick has been studied using microfocus synchrotron X-ray fluorescence (SXRF) at I18 at Diamond Light Source. As described in The Journal of Inorganic Biochemistry, researchers saw that the drug penetrated ovarian cancer cell spheroids and the distribution of zinc and calcium was perturbed.
Platinum-based chemotherapy agents are used to treat many cancer patients, but some can develop resistance to them. To address this issue, scientists from the University of Warwick sought to employ alternative precious metals. They developed an osmium-based agent, known as FY26, which exhibits high potency against a range of cancer cell lines. To unlock the potential of this novel agent and to test its efficacy and safety in clinical trials, the team need to fully understand its mechanism of action.
To explore how FY26 behaves in tumours, the team grew ovarian cancer spheroids and used SXRF at I18 to probe the depth of penetration of the drug. They noted that FY26 could enter the cores of the spheroids, which is critical for its activity and very encouraging for the future of the drug. SXRF also enabled them to probe other metals within the cells, which showed that the distribution of zinc and calcium was altered, providing new insights into the mechanism of FY26-induced cell death.
A century after the invention of radio, the oscillating electric fields initially generated for communication now perform a fundamental function in all accelerators.
Instead of being broadcast to the world, radiofrequency (RF) energy at Diamond is trapped in resonating metal cavities to generate the electric fields that bring Diamond’s electrons up to speed.
The journey of an electron from source to storage ring is a tale of high power, split-second timing and frankly terrifying voltages. It begins in the linac gun where energetic, hot electrons are sucked away from a metal cathode by 90,000 volts and directed into the linear accelerator, or linac. The electrons travel down the linac together with precisely timed 16 megawatt blasts of microwaves generated by klystron amplifiers that themselves operate at pulsed voltages in excess of 200,000 volts. Electrons are accelerated towards the speed of light in the linac and then injected into the booster synchrotron where they complete many orbits over a tenth of a second.
Image: The linac, with the gun at the far end and the accelerating structures coming towards us.