First structure of a DNA crosslink repair ligase determined

Diamond’s Electron Bio-Imaging Facility (eBIC) has been used to generate the first 3D structure of the Fanconi anaemia (FA) core complex, a multi-subunit E3 ubiquitin ligase required for the repair of damaged DNA. The work, led by Dr Lori Passmore from the MRC Laboratory of Molecular Biology and a team of researchers, has been published today in Nature, and their research provides the molecular architecture of the FA core complex and new insights into how the complex functions.

The FA pathway senses and repairs DNA crosslinks that occur after exposure to chemicals including chemotherapeutic agents and alcohol, but also as a result of normal cellular metabolism. The megadalton FA core complex acts as an E3 ubiquitin ligase to initiate removal of these DNA crosslinks, helping to repair the damage caused. The research team used eBIC’s imaging facilities to make a major breakthrough in understanding the FA core complex by determining its structure using an integrative approach including cryo-electron microscopy and mass spectrometry.

Dr Peijun Zhang, Director of eBIC notes that:

Enabling cutting-edge research like this is exactly why we established eBIC, to provide scientists with state-of-the-art experimental equipment and expertise in the field of cryo-electron microscopy, for both single particle analysis and cryo-electron tomography. Determining the structure of the FA core complex for the first time is a fantastic achievement for the MRC research team.

>Read more on the Diamond Light Source website

Image: The FA core complex.
Credit: Phospho Biomedical Animation

Suspending sample droplets with sound waves

TinyLev offers a cheap and portable way to use acoustic levitation at synchrotron beamlines.

Acoustic levitation suspends matter using acoustic radiation pressure to balance the force of gravity. It has potential applications in crystallography, spectroscopy, chemistry, and the study of organisms in microgravity. However, conventional acoustic levitation systems rely on Langevin horns, which are large and expensive pieces of equipment that are complicated to set up. TinyLev, initially developed by researchers at the University of Bristol, is a small single-axis non-resonant acoustic levitator constructed from off-the-shelf components. In work recently published in Scientific Reportsengineers at Diamond led by Dr Pete Docker used the TinyLev system to dispense and contain sample droplets in protein crystallography experiments. Their novel method facilitates efficient X-ray data acquisition in dynamic studies at room temperature.

>Read more on the Diamond Light Source website

Picture: Left: Photograph showing the TinyLev system mounted on the I24 beamline with the X-ray beam path marked with a yellow dashed arrow. Components as labelled: (A) High-magnification viewing system, (B) X-ray scatter-guard, (C) levitating drop, (D) beamstop (out of position), (E) TinyLev Transducer array, (F) backlight (retracted during data collection), (G) sample positioning stage. Right: Model of the acoustic levitation system (E) used in this work annotated with key dimensions and showing the focal point of the transducer array.

Worldwide scientific collaboration develops catalysis breakthrough

A new article  just published in Nature Catalysis shows the simple ways of controlling the structure of platinum nanoparticles and tuning their catalytic properties. 

Research led by Cardiff Catalysis Institute (CCI) in collaboration with scientists from Lehigh University, Jazan University, Zhejiang University, Glasgow University, University of Bologna, Research Complex at Harwell (RCaH), and University College London have combined their unique skills to develop and understand using advanced characterisation methods (particularly TEM and B18 at Diamond Light Source), how it is possible to use a simple preparation method to control and manipulate the structures of metal nanoparticles. These metal nanoparticles are widely used by industry as innovative catalysts for the production of bulk chemicals like polymers, liquid fuels (e.g., diesel, petrol) and other speciality chemicals (pharmaceutical products).

>Read more on the Diamond Light Source website

Image: Andy Beale works at Diamond Light Source.

Pirbright Institute grants a new licence for FMDV vaccine development

The Pirbright Institute and its research partners have granted MSD Animal Health an exclusive commercial licence for a new, effective and affordable vaccine to protect livestock against several serotypes of foot-and-mouth disease virus (FMDV). The new vaccine is more stable than current foot-and-mouth disease (FMD) vaccines and is less reliant on a cold-chain during vaccine distribution – characteristics that give the vaccine greater potential for helping to relieve the burden placed on regions where the disease is endemic in large parts of Africa, the Middle East and Asia. These developments have been possible, thanks to a long-standing collaboration between Diamond Light Source, Pirbright, the University of Oxford, the University of Reading and MSD Animal Health, and the vaccine has been developed over the years from basic science to animal trials. This work has been supported by funding from the Wellcome Trust to speed up commercialisation.

Professor David Stuart, Life Sciences Director at Diamond Light Source and MRC Professor in Structural Biology at the University of Oxford, noted:

We have been working to achieve something close to the holy grail of vaccines. Instead of traditional methods of vaccine development, using infectious virus as its basis, our team synthetically created empty protein shells to imitate the protein coat that forms the strong outer layer of the virus. Diamond’s visualisation capabilities and the expertise of Oxford University in structural analysis and computer simulation, enabled us to visualise in detail something invisible in a normal microscope and to enhance the design, atom by atom, of the empty shells. The key thing is that unlike the traditional FMDV vaccines, there is no chance that the empty shell vaccine could revert to an infectious form. The licence that has just been granted suggests that the work will have a broad and enduring impact on vaccine development.

>Read more on the Diamond Light Source website

Diamond shines its light on Moon Rocks, Martian meteorites & Vesta

An international collaboration involving scientists in Tenerife, the US and the UK, have used Diamond Light Source, the UK’s national synchrotron to investigate the effect of gravity on rocky planets. They examined three billion+ year old rocks from the Moon collected during the Apollo missions, as well as meteorites from Mars, Vesta, and other environments collected in Antarctica.
The team – led by Dr Matt Pankhurst, Instituto Volcanológico de Canarias/(the Canarian Volcanlogical Institute (INVOLCAN) with co-investigators Dr Ryan Zeigler, NASA; Dr Rhian Jones, University of Manchester; Dr Beverley Coldwell, ITER; Dr Hongchang Wang, Diamond Light Source; Dr Robert Atwood, Diamond Light Source and Dr Nghia Vo, Diamond Light Source – aims to use the samples to make comparisons between processes and timescales that form similar rocks that are collected from different gravitational conditions.

Diamond’s 8000th publication: The future of solar cells

A collaboration between researchers in the UK and China recently led to the publication of the 8000th research article describing cutting edge science carried out at Diamond Light Source. Professor David Lidzey from the University of Sheffield and his collaborator Professor Tao Wang from Wuhan University of Technology published their findings in Nano Energy with implications for the future of solar cells.
Fullerene molecules known as “Bucky balls” have been used as charge acceptors in solar cells for a long time. Researchers used Diamond Light Source to investigate new acceptor molecules that would be cheaper to manufacture. They discovered that depending on the molecule and the way that it was blended with polymers, they were able to see a significant efficiency increase over traditional compositions. The added efficiency came from the fact that the new compositions could absorb light over a broader wavelength range. This means that if used in solar cells, they will be able to use more of the sun’s light than is possible using current materials.
The added efficiency comes from the molecules themselves as well as the way they are blended and cast. Using the GWAXS technique at Diamond, the researchers found that flat acceptor molecules were able to stack very efficiently and that the production method allowed them to self-organise on nanometre length scales allowing aggregates to form that extend the wavelengths that can be absorbed.

>Read more on the Diamond Light Source website

Image: A representation of a “bucky ball” or fullerene molecule, commonly used as charge acceptors in solar panels.

Feeling the strain: shear effects in magnetoelectric switching

Diamond uncovers unexpected complexity that may aid magnetoelectric data storage devices.

The high resolution and wealth of data provided by an experiment at Diamond can lead to unexpected discoveries. The piezoelectric properties of the ceramic perovskite PMN-PT (0.68Pb(Mg1/3Nb2/3)O3–0.32PbTiO3) are widely used in commercial actuators, where the strain that is generated varies continuously with applied voltage. However, if the applied voltage is cycled appropriately then there are discontinuous changes of strain. These discontinuous changes can be used to drive magnetic switching in a thin overlying ferromagnet, permitting magnetic information to be written electrically. An international team of researchers used beamline I06 to investigate a ferromagnetic film of nickel when it served as a sensitive strain gauge for single-crystal PMN-PT. Their initial interpretation of the results suggested that ferroelectric domain switching rotated the magnetic domains in the film by the expected angle of 90°, but a closer examination revealed the true picture to be more complex. Their work, recently published in Nature Materials, shows that the ferroelectric domain switching rotated the magnetic domains in the film by considerably less than 90° due to an accompanying shear strain. The findings offer both a challenge and an opportunity for the design of next-generation data storage devices, and will surely be relevant if the work is extended to explore the electrically driven manipulation of more complex magnetic textures.

>Read more on the Diamond Light Source website

Image: Magnetic vector map (50 µm field of view) describing the magnetisation of a Ni film while applying 50 V across the ferroelectric substrate of PMN-PT. The colour wheel identifies magnetisation direction. Yellow and brown denotes regions whose magnetisation was unaffected by the voltage.

Potassium hunting on protein factories

Amazing insights into the location of elusive potassium ions on bacterial ribosomes

Groundbreaking research at the new long-wavelength macromolecular crystallography beamline (I23) at Diamond Light Source has for the first time demonstrated the location of potassium ions in bacterial ribosomes. Ribosomes are the protein factories of cells and although they are vital for life, little was known of the sites of metal ions that are crucial for their structure and function. The work recently published in Nature Communications showcases the fantastic applications of the I23 beamline and sheds light on the important role of potassium ions.

>Read more on the Diamond Light Source website

Image: (extract, full image here) 70S ribosome elongation complex (potassium atoms rendered as green spheres).

How stained glass can help in the battle against superbugs

Ancient skills meet cutting edge technology in the battle against antibiotic resistance

Bacteria can form colonies (known as biofilms) on the surface of objects. This is a particular problem when it occurs on medical devices implanted into the body, such as catheters, prosthetic cardiac valves and intrauterine devices, as biofilms can display resistance to both antibiotics and the body’s immune response. Any incision into the body risks a surgical infection, and if a biofilm takes hold it can be difficult to eradicate. With the rise in antibiotic resistance, scientists are seeking new ways to prevent infections, and there is increasing interest in impregnate medical devices with antimicrobial substances. In work recently published in ACS Biomaterials Science & Engineering, researchers from Aston University in Birmingham, led by Dr Richard Martin, explored the antimicrobial potential of phosphate glasses doped with cobalt, and found them to be effective against Escherichia coli, Staphylococcus aureus and Candida albicans when placed in direct contact, suggesting that cobalt-doped bioactive glasses could be developed with antimicrobial properties. The technique they discovered is similar to those used to make stained glass in medieval times.

>Read more on the Diamond Light Source website
Image: Images of the copper (left) and cobalt (right) doped bioactive glasses.
Credit: Dr Richard Martin

A novel synchrotron technique for studying diffusion in solids

Bragg coherent diffraction imaging (BCDI) offers insights for nanoparticle synthesis

Understanding and controlling how the diffusion process works at the atomic scale is an important question in the synthesis of materialsFor nanoparticles, the stability, size, structure, composition, and atomic ordering are all dependent on position inside the particle, and diffusion both affects all of these properties and is affected by them. A more thorough understanding of the mechanisms and effects of diffusion in nanocrystals will help to develop controlled synthesis methods to obtain the particular properties; however, conventional methods for studying diffusion in solids all have limitations.
Given the need for imaging techniques that are sensitive to slower dynamics and allow the diffusion behaviour in individual nanocrystals to be investigated at the atomic scale and in three dimensions (3D), a team of researchers used the strain sensitivity of Bragg coherent diffraction imaging (BCDI) to study the diffusion of iron into individual gold nanocrystals in situ at elevated temperatures. Their work was recently published in the New Journal of Physics.

Image, third of three figures: Reconstructed amplitude and phase images near the centre of the nanocrystals before and after iron deposition (1 pixel = 16.28 nm). The direction of the Q-vector, which is along the (11-1) direction, is shown by the arrow in the control phase images. See all here.
DOI:10.1088/1367-2630/aaebc1

Synchrotron techniques allow geologists to study the surface of Mars

State-of-the-art imaging uncovers the exciting life history of an unusual Mars meteorite

With human and sample-return missions to Mars still on the drawing board, geologists wishing to study the red planet rely on robotic helpers to collect and analyse samples. Earlier this year we said goodbye to NASA’s Opportunity rover, but Insight landed in November 2018, and several space agencies have Mars rover missions on their books for the next few years. But while we’re working on ways to bring samples back from Mars, geologists can study Martian meteorites that have been delivered to us by the forces at play in the Solar System. Earth is bombarded by tonnes of extraterrestrial material every day. Most of it comes from Jupiter Family Comets and the asteroid belt, and much of it burns up in the atmosphere or lands in the oceans, but meteorites from the Moon and Mars do make it to Earth’s surface. In research published in Geochimica et Cosmochimica Acta, scientists used a battery of synchrotron techniques to investigate a very unusual Martian meteorite, whose eventful life story offers some insights to the geological history of Mars.

>Read more on the Diamond Light Source website

Image: BSE image with locations for XANES/XRD and XRF map.

Understanding the viruses that kill cancer cells

Taking inspiration from virology to find better treatments for cancer

There are some viruses, called oncolytic viruses, that can be trained to target and kill cancer cells. Scientists in the field of oncolytics want to engineer these viruses to make them safer and more effective so they can be used to treat more people and different types of cancers. To achieve this, they first have to fully understand at the molecular level all the different ways that the virus has evolved to infect healthy cells and cause disease. A research team from Cardiff University set out to better understand how a protein on the surface of a virus often used to kill cancer, called an adenovirus, binds to human cells to cause an infection. Using X-ray crystallography, the team was able to determine the structure of one the key adenovirus proteins. Using this information and after extensive computational analysis, the research team realised the virus was not binding the receptor on the cells that was originally thought. This has important implications for the development of new virotherapies and engineering of viruses to treat cancer. The more thoroughly the researchers can understand how the adenoviruses interact with cancer cells at the molecular level, the more safe and effective treatments can be brought to clinical trial in the future.

>Read more on the Diamond Light Source website

Imaging dendrite growth in zinc-air batteries

SXCT captures unprecedented detail of dendrite formation, growth and dissolution

Modern life runs on rechargeable batteries, which power all of our mobile devices and are increasingly used to power vehicles and to store energy from renewable sources. We are approaching the limits of lithium-ion battery technology in terms of maximum energy capacity, and new technologies will be needed to develop higher capacity rechargeable batteries for the future. One class of promising candidates is metal-air batteries, in particular zinc-air batteries that have a high theoretical energy density and low estimated production costs. However, zinc-air batteries present certain challenges, in key areas such as cycle life, reversibility and power density. The formation of metal dendrites as the battery charges is a common cause of failure, as dendrites can cause internal short circuits and even thermal runaway. (Thermal runaway is a sequence of exothermic reactions that take place within the battery, leading to overheating and potentially resulting in fire or an explosion. It is also a problem in lithium-ion batteries, and the subject of ongoing research.) In work recently published in Joule, a team of researchers from Imperial College, London, University College London, the University of Manchester and the Research Complex at Harwell carried out in situ experiments investigating how dendritic growth can cause irreversible capacity loss, battery degradation and eventually failure.
>Read more on the Diamond Light Source website

Image: (extract, see full image here) Single dendrite and dendritic deposits inside and on top of the separator (FIB-SEM)

Funding research crucial to Africa: Energy and healthcare

The 27th March 2019 saw the official launch of START (Synchrotron Techniques for African Research and Technology), a £3.7M grant awarded to a consortium of researchers led by Diamond Light Source by the Science and Technology Facilities Council (STFC) to work with African scientists on START.

Africa does not yet have a synchrotron light source, but African researchers are keen to apply synchrotron techniques to their research problems. The START project will fund research posts in Africa and the UK with a focus on two key areas crucial to development in Africa – energy and healthcare . The scientific results that come out of the project will be valuable in themselves, and may also lead to commercial applications, but START will also promote the development of research capabilities within Africa, and international research collaborations.

For Diamond Principal Investigator, Prof. Chris Nicklin, this will be the most important result: It is an exciting prospect to work together on these challenging problems and this funding will enable us to form very strong links at all levels, in particular helping to train the next generation of researchers in nations that have not had the chance to access and exploit synchrotron based techniques in their research. The work will focus around the development needs of African countries, driven by the Africa-based investigators and the non-government organisations (NGOs) that we have on board.

>Read more on the Diamond Light Source website

X-ray fluorescence sheds light on the growth patterns of extinct hyaena

A novel synchrotron technique examines growth patterns in fossil bones

Until recently, it was thought that warm-blooded animals experienced uninterrupted high rates of growth, whilst cold-blooded animals showed zonal growth – alternating periods of fast and slow growth. The identification of zonal growth in a range of mammals and birds disproved that theory, but as yet we don’t know how widespread zonal growth is in vertebrates, or which factors affect the speed of bone growth. Conventional techniques lack the resolution to correlate variations in bone chemistry with histological features, but in work recently published in the Journal of Analytical Atomic Spectrometry, an international team of researchers carried out the first direct comparison between optical histology (bone tissue identification) and synchrotron-based chemical mapping, quantification, and characterisation of trace elements (biochemistry) within cyclic growth tissues, and reported the first case of zonal tissue within the Hyaenidae.

>Read more on the Diamond Light Source website

Image: Lead author Jennifer Anné with a spotted hyaena mount.

A step closer to early detection of multiple sclerosis

Synchrotron techniques identify the critical conditions that alter myelin structure

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease resulting in the destruction of myelin, a fatty substance that insulates nerves and increases the speed at which signals travel between nerve cells. MS affects more than 2.3 million people worldwide and has no cure. In work recently published in PNAS, a team of researchers from Tel Aviv University and the Technion-Israel Institute of Technology mapped, for the first time, the delicate and complicated force balance between the myelin sheath constituents, and their effect on the myelin structure. This new information will allow the identification of critical components involved in neurodegenerative diseases such as MS.