Insights into an antibody directed against dengue virus

We are one step further to uncovering a new way to stave off dengue fever thanks to important work carried out at the I02 beamline at Diamond Light Source.

The study, recently published in Nature Immunology, describes how an antibody effectively targets the dengue virus.
Dengue virus affects hundreds of millions of people worldwide and is an untreatable infection. Secondary infections with dengue can lead to a life-threatening form of the disease due to a phenomenon called antibody-dependent enhancement (ADE). Additionally, efforts to develop a vaccine against the virus have been hindered by ADE.

A huge collaborative effort sought to investigate ADE in dengue, and two antibodies were characterised that bound to the envelope protein of the dengue virus. One of the antibodies was found to be a potent neutraliser of the virus, but importantly was unable to promote ADE.

>Read more on the Diamond Light Source website

Image: Fab binding in the context of the mature virion. e, Comparison of 2C8 Fab and 3H5 Fab docked onto a E dimer. 2C8 (green) and 3H5 (orange) Fabs were docked onto PDB ID 3J27 by aligning the EDIII potion of the structures. The Fabs are shown as surfaces and the E dimer is displayed in cartoon representation. A side view is of the E dimer on the viral surface is shown. The approximate location of the viral membrane is shown schematically.

 

A guide to central nervous system tomography

In-depth investigations on I13 to optimise soft tissue synchrotron X-ray microtomography

The Bradbury Lab at King’s College London, headed by Professor Elizabeth Bradbury, investigates damage to the central nervous system (CNS), and how the body responds to it. The traditional way of investigating soft tissue samples such as those of the central nervous system is 2D histology, in which slices are taken, stained and imaged. However, this process has limitations – slice thickness has a lower limit and measurements within cut slices are subject to inaccuracies arising from mechanical processing distortions. The group sent PhD student (now Dr) Merrick Strotton to the Diamond-Manchester Imaging Branchline I13-2 to investigate whether X-ray microtomography (a nominally non-destructive technique for taking a series of 2D images and turning them into a 3D volume) could avoid these issues. It wasn’t clear how to achieve the best possible results, and so alongside the biomedical studies, Dr Strotton worked with Diamond’s Dr Andrew Bodey on a series of methodological investigations on how to optimise imaging for soft tissue samples, the first results of which have recently been published in Scientific Reports.

>Read more on the Diamond Light Source website

Image: Segmentation of the low thoracic-high lumbar (T13-L1) level spinal cord sample from background, white & grey matter from spinal cord and vasculature from spinal cord with SuRVoS.
Credit: https://www.nature.com/articles/s41598-018-30520-8#Sec10

Year of Engineering I23 Gripper Spotlight

Celebrating the Year of Engineering on Beamline I23

The Year of Engineering (UK) is all about celebrating the world and wonder of the industry, and exploring the wide range of ideas and innovations that Engineering involves. Today, we’re having a look at Diamond’s Beamline I23 – a specially designed instrument for protein crystallography that uses long wavelengths.
There are unique engineering scientific challenges involved in designing a system that will allow researchers to use long wavelengths of Synchrotron radiation effectively. The special cryogenically-cooled sample gripper on I23, is one of the solutions that makes this beamline successful. Learn more about this engineering innovation.

>Read more and watch more videos on the Diamond Light Source website

Diamond shines its light on moon rocks

Nearly 50 years after our first steps on the Moon, rock samples from the Apollo missions still have a lot to tell us about lunar formation, and Earth’s volcanoes.

An international collaboration involving scientists in Tenerife, the US and the UK, are using Diamond, the UK’s national synchrotron light source, to investigate Moon rocks recovered during the Apollo Missions in a brand new way.
Dr. Matt Pankhurst of Instituto Volcanológico de Canarias and NASA lunar principle investigator explains: “We have used a new imaging technique developed at Diamond to carry out 3D mapping of olivine – a common green mineral found in the Earth’s sub-surface and in these Moon rock samples. These maps will be used to improve understanding of the Moon’s ancient volcanic systems and help to understand active geological processes here on Earth.
With this new technique, our team may be able to recover from these Moon rock samples information such as what the patterns of magma flow within the volcanic system were, what the magma storage duration was like, and potentially even identify eruption triggers. The data will be analysed using state-of-the-art diffusion modelling which will establish the history of individual crystals.”

>Read more on the Diamond Light Source website

Image:
Dr Matt Pankhurst studies one of the moon rock samples from the Apollo 12 & 15 missions at Diamond Light Source

Diamond’s light illuminates our Anglo-Saxon heritage

Oakington is a small, village seven miles north-west of Cambridge. Archaeological finds in the area suggest that there may have been a settlement here in the Stone Age. In 1926, horticulturalist Alan Bloom was digging at his new nursery in Oakington when he uncovered three early Anglo-Saxon burials. In the 1990s, Cambridge County Council’s Archaeological Field Unit uncovered 24 more burials, which had been discovered during the construction of a children’s playground.
Wondering what else was hidden under the Fens, archaeologists from Oxford Archaeology East (then known as CAMARC) found 17 more burials in 2006/7. And in 2010/11, a further 27 burials were found in new trenches around the playground, including the remains of children, which are rare finds from this period. The most recent excavations were part of the ‘Bones without Barriers’ project, which encourages community communication and participation.

New cryo-EM Collaboration

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.”

>Read more on the Diamond Light Source website

Image: Close up sample loading Krios I.

A closer look of zink behaviour under extreme conditions

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.

These results can help to understand the processes and phenomena happening in the Earth’s interior.

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.

>Read more on the ALBA website

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. 

Nanoparticles form supercrystals under pressure

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.

>Read more on the Diamond Light Source website

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. 

Strain research on rotating bearings wins Fylde prize for best paper

The paper – “Dynamic contact strain measurement by time‐resolved stroboscopic energy dispersive synchrotron X‐ray diffraction,” was the result of a collaboration between the Universities of Sheffield, Bristol, Oxford and Diamond Light Source. The researchers set themselves the challenge not just of measuring the strain in a bearing, but of capturing the measurement while the bearing was rotating and under load. This involved using a special stroboscopic X-ray diffraction technique to measure the strain in the rotating piece of machinery.
The authors will receive their award from the Journal’s Editorial Board and the British Society for Strain Measurement (BSSM) on 30th August 2018 and have been invited to present their paper at the BSSM’s International Conference on Advances in Experimental Mechanics in Southampton at 29 – 31 August 2018.
Image: The bearing experiment.

Magnetic vortices observed in haematite

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.

>Read more on the Diamond Light Source website

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.

Demonstrating a new approach to lithium-ion batteries

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.

>Read more on the Diamond Light Source website

Scientists unravel mechanism for body odour in armpits

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.”

>Read more on the European Synchrotron (ESRF) website

Image: Picture showing how body odour is produced in armpits.
Credit: University of York and Oxford. 

3D X-ray tomography scoops up information about ice cream

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.

>Read more on the Diamond Light Source website

Angular measurement goes nano

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.

Imagine a 1m long spirit level set on a flat surface, then place a 1mm spacer under one end. That gives an angular change of 1/1,000 of a radian or 1 milliradian. Radians are an alternative way of describing angles instead of degrees.

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.

Image: Diamond-NANGO, with its rotation axis pointing in the horizontal direction.

How legionella manipulates the host cell by means of molecular mimics

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.

>Read more on the ALBA website

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)