Trigger of rare blood clots with AstraZeneca and other COVID vaccines found by scientists

understanding rare blood clots caused by some  COVID vaccines – important first to prevention

A collaborative team from the School of Medicine at the University of Cardiff, Wales and a range of US institutions used the UK’s national synchrotron, Diamond Light Source, to help reveal the details of how a protein in the blood is attracted to a key component of Adenovirus based vaccines.  

It is believed this protein kicks off a chain reaction, involving the immune system, that can culminate in extremely rare but dangerous blood clots. The Cardiff team were given emergency government funding to find the answers. In collaboration with scientists in the US and from AstraZeneca, they set out to collect data on the structure of the vaccines and perform computer simulations and related experiments to try and uncover why some of the vaccines based on Adenoviruses were causing blood clots in rare cases.  

Moderna and BioNTech are based on mRNA, whereas AstraZeneca and Johnson & Johnson are based on Adenoviruses. Blood clots have only been associated with vaccines that use Adenoviruses.

Read more on the Diamond website

Image: Crystallisation of ChAdOx1 fibre-knob protein results in 4 copies of the expected trimer per asymmetric unit and reveals side-chain locations. The crystal structure was solved with 12 copies of the monomer in the asymmetric unit, packing to form 3 trimeric biological assemblies. Density was sufficient to provide a complete structure in all copies.

Credit: Image reused from DOI: 10.1126/sciadv.abl8213 under the CC BY 2.0 license. 

Collaboration: a watchword for the light source community

Scientists Nina Perry and Nina Vyas, from Diamond Light Source (https://diamond.ac.uk – the UK’s synchrotron), along with SaeHwan Chun, scientist at the PAL-XFEL (https://pal.postech.ac.kr/paleng/ – the Free Electron Laser in South Korea) talk about a theme that is common to all light sources around the world, and indeed to science and all its associated disciplines. Cooperation and collaboration, and their benefits for scientists’ wellbeing as well as the science, are highlighted in this #LightSourceSelfie video.

Nina Perry & Ninya Vyas, on Beamline B24 at Diamond Light Source, the UK’s synchrotron science facility

Paving the way for more effective pancreatic cancer research

A team of scientists led by the University of Surrey used Diamond’s B16 Beamline, a flexible and versatile beamline for testing new developments in optics and detector technology and for trialling new experimental techniques, to better understand the structure of cancer cells. 

By using the synchrotron, the team were able to complete sophisticated examinations of the characteristics of cell structures at a nano level and even at an atomic scale and to investigate how cells and materials interact with each other.  

To improve cancer screening and treatment, researchers need accurate models of cancer tissues on which to experiment. Previous research made significant progress in building accurate, novel 3D models which mimic features of a pancreatic tumour, such as structure, porosity and protein composition.

Read more on the Diamond website

Image: Inside the experimental hutch at Diamond’s B16 beamline.

Credit: Diamond Light Source

Developing unbreakable screens

Cracked phone screens could become a thing of the past thanks to breakthrough research by a global team of scientists

Diamond’s electron Physical Science Imaging Centre (ePSIC) was used in a study that has unlocked the technology to produce next-generation composite glass for lighting LEDs as well as smartphone, television and computer screens. 

The research was recently published in the journal Science and was carried out by an international collaboration involving scientists and engineers from the University of Queensland, University of Leeds, University of Cambridge and Université Paris-Saclay. The findings will enable the manufacture of glass screens that are not only unbreakable but also deliver crystal clear image quality.  

Better LEDs 

The study is focused on nanocrystal materials known as lead halide perovskites, which are promising candidates for light emitting diodes. A powerful electron microscope at ePSIC allowed the team to study the structure of this material. The breakthrough has been the ability to stabilise a particular crystal at room temperature.   

Read more on the Diamond website

Image: Examples of the fabricated glass composite shown under a UV light (black light) to reveal the emission of bright and pure colours. The colour of light emitted from each sample is determined by the chemistry and the size of the nanocrystals embedded in a metal-organic framework glass.

Credit: University of Queensland.

Nano-precision metrology of X-ray mirrors

Synchrotrons work like a giant microscope, and they both need mirrors and lenses to bend and shape light. The better control we have over the light source, the more we can see. The quality of images that can be captured using a microscope or a synchrotron rely heavily on the optics used.

As technology has advanced over the past few decades and as synchrotron users push the boundaries of what can be achieved, there has been a lot of excitement over the upgrades of synchrotron mirrors and what that can mean for the experiments that can be done.

However, there is a bottleneck for the production of new and improved X-ray optics like mirrors. It turns out that it is hard to develop metrology instruments that can validate and measure the quality of new high-precision mirrors. Producing these instruments and alleviating the bottleneck is the goal of the metrology community, as they say, if you cannot test something, you cannot manufacture it.

Using the properties of speckle to get better measurements

The metrology community has made significant advances by making improvements to existing techniques to test X-ray mirrors. However, a team from Diamond set about creating a brand-new instrument which can potentially improve the toolbox for metrologists and manufacturers around the world.

Read more on the Diamond website

Image: Dr Hongchang Wang (Left) is supervising his PhD student Simone Moriconi (Right) for testing SAM system

Science Advances cover dedicated to research results on Cryo-EM

The research carried out at NCPS SOLARIS with the use of electron cryomicroscopy and at the Malopolska Biotechnology Centre, and at the British National Electron Bioimaging Center eBIC (Diamond Light Source) allowed to solve the structure of the protein responsible for introducing compounds necessary for the life of bacterial cells. The exceptional importance of the research was honored with a dedicated, unique image by Alina Kurokhtina published on the cover of Science Advances!

Bacterial species are under continuous warfare with each other for access to nutrients. To gain an advantage in this struggle, they produce antibacterial compounds that target and kill their competitors. Different species of bacteria, including ones that live inside us, can battle each other for scarce resources using a variety of tactics. Now, researchers from the laboratories of Prof Jonathan Heddle from Malopolska Centre of Biotechnology, Jagiellonian University, Krakow and Dr Konstantinos Beis at Research Complex at Harwell /Imperial College, London, have uncovered the mechanism of one such tactic in work that may eventually lead to the development of new antibacterials.

Read more on the SOLARIS website

Image: A view of the determined SbmA structure in gold

Credit: Alina Kurokhtina

Molecular IgG3 structure paves the way for new applications of antibodies

A combination of scattering and analytical techniques has provided the first atomic-level structural model for the IgG3 antibody

In humans, Immunoglobulin (IgG) is the most common type of antibody found in blood circulation. IgG molecules are created by plasma B cells, and there are four subclasses. Of the four, IgG3 is the least understood. It has a uniquely long hinge region separating its Fab antigen-binding and Fc receptor-binding regions. The presence of this elongated hinge makes it challenging to perform structural studies, for example, with X-ray crystallography. Due to this lack of structural information, IgG3 is the only subclass not currently exploited for therapeutic uses. In work recently published in the Journal of Biological Chemistry, researchers from University College London and the University of Birmingham have used a combination of imaging and analytical methods to provide the first experimentally determined molecular structural model for a full-length IgG3 antibody. This new information should enable the use of IgG3 to develop new therapies and antibody tests. 

Getting a good look at IgG3

A high-resolution structure for part of the IgG3 molecule, the globular IgG3-Fc fragment, is available. And previous studies of the whole molecule using Small Angle X-ray Scattering (SAXS) and analytical ultracentrifugation (AUC) showed that IgG3 is elongated compared to IgG1, IgG2 and IgG4. SAXS also showed that IgG3 has a more extended central hinge than IgG1 and IgG2 that links its three globular regions together.  

Read more on the Diamond website

Image: The IgG3 structural model is formed from two globular Fab regions, a long hinge in the centre, and one Fc region, as shown from the scattering modelling fits. The structure is reminiscent of a giraffe with an extended and semi-rigid neck.

Credit:
Dr Valentina Spiteri, UCL.

Diamond-II programme set to transform UK science

Diamond Light Source has established itself as a world-class synchrotron facility enabling research by leading academic and industrial groups in physical and life sciences. Diamond has pioneered a model of highly efficient and uncompromised infrastructure offered as a user-focussed service driven by technical and engineering innovation.

To continue delivering the world-changing science that Diamond leads and enables, Diamond-II is a co-ordinated programme of development that combines a new machine and new beamlines with a comprehensive series of upgrades to optics, detectors, sample environments, sample delivery capabilities and computing. The user experience will be further enhanced through access to integrated and correlative methods as well as broad application of automation in both instrumentation and analysis. Diamond-II will be transformative in both spatial resolution and throughput and will offer users streamlined access to enhanced instruments for life and physical sciences.

Read more on the Diamond website

Image: Diamond’s synchrotron building

Credit: Diamond Light Source

Critical data of insect specimens to be unlocked through 3D imaging

The Natural History Museum is collaborating with Diamond Light Source, the UK’s national synchrotron science facility, on an ambitious project to generate and share immense data from the Museum’s vast insect collections to help further research into their evolution, diversity and extinctions. The Natural History Museum is collaborating with Diamond Light Source, the UK’s national synchrotron science facility, on an ambitious project to generate and share immense data from the Museum’s vast insect collections to help further research into their evolution, diversity and extinctions.

Over 1.6 million of the Museum’s 35 million insects have already been digitised using 2D photography. These specimens have had their images and collections data (information about where in time and space they were collected and what species they are) made available to the public via the Museum’s Data Portal. However, this landmark project is expected to provide valuable new insights and information by providing the beginnings of a high-resolution 3D dataset for all living and fossil insects and their close relatives.

Read more on the Diamond website

Image: Hairy Fungus Beetle – Prepared by Malte Storm

Credit: Diamond Light Source Ltd

Diamond helps find a way to improve accuracy of Lateral Flow Tests

A recent study has found a way to help reduce false-negative results in Lateral Flow Tests by a simple modification.

Using X-ray fluorescence imaging at Diamond, researchers from King’s College London set out to identify what could be causing these false-negative results, and what potential modifications could enable increased accuracy.

They identified that the underlying technology of the Lateral Flow Devices is highly accurate and able to theoretically detect trace amounts of the COVID-19 virus, but the limitations fall to the read-out of the device – the technology used to communicate the result of the test.

The study, published in ACS Materials and Interfaces, suggests  several potentially simple modifications to the Lateral Flow Devices that could lead to improved performance.

read more on the Diamond website

Diamond helps discover microscopic metallic particles in the brain

A UK-led international team of researchers has discovered elemental metallic copper and iron in the human brain for the first time. The team, comprised of scientists from Keele University and the University of Warwick in collaboration with the University of Texas at San Antonio (UTSA), used Diamond, and the Advanced Light Source located in California (USA) to identify elemental metallic copper and magnetic elemental iron within the amyloid plaques, chemical forms of copper and iron previously undocumented in human biology.

The study, published in Science Advances and funded by the UKRI’s Engineering and Physical Sciences Research Council, looked at amyloid plaques isolated from the brain tissue of deceased Alzheimer’s patients. Amyloid plaques, a hallmark feature of Alzheimer’s disease, act as a site of disrupted metal chemistry in the Alzheimer’s brain, and are believed by many to be integral to disease progression.

Read more on Diamond website

Image: X-ray microscope images and X-ray absorption spectra obtained from two Alzheimer’s disease plaque cores, measured at Diamond’s beamline I08. Image: Science Advances.

Credit: Science Advances.

Physicists uncover secrets of world’s thinnest superconductor

Physicists report the first experimental evidence to explain the unusual electronic behaviour behind the world’s thinnest superconductor, a material with myriad applications because it conducts electricity extremely efficiently. In this case the superconductor is only an atomic layer thick. 

The research, led by Massachusetts Institute of Technology and Brookhaven National Laboratory, was possible thanks to new instrumentation available at Diamond.  

Diamond is one of only a few facilities in the world to use the new experimental technique, Resonant Inelastic X-ray Scattering (RIXS), which is a combination of X-ray Absorption Spectroscopy (XAS) and X-ray Emission Spectroscopy (XES), where both the incident and emitted energies are scanned. This state-of-the-art facility is where the team from three continents conducted their experiment.  

Read more on the Diamond website

Image: Members of the RIXS team at Diamond. Left to right: Jaewon Choi (Postdoc), Abhishek Nag (Postdoc), Mirian Garcia Fernandez (Beamline Scientist), Charles Tam (joint PhD student), Thomas Rice (Beamline technician), Ke-Jin Zhou (Principal Beamline Scientist), Stefano Agrestini (Beamline Scientist).

Report reveals impact of over £1.8bn on UK science & economy by Diamond

A recent study by Technopolis and Diamond estimates a cumulative monetised impact of at least £1.8 billion from the UK’s synchrotron, reflecting very favourably with the £1.2 billion investment made in the facility to date.  And it costs less than a cup of coffee as each taxpayer contributes only £2.45 a year towards it.  The study, published today (26 May), set out to measure and demonstrate Diamond’s scientific, technological, societal, and economic benefits.  The report summarises the findings and highlights the significant impact it has achieved to date.  

Diamond’s mission is to keep the UK at the forefront of scientific research. We do this by providing our users in academia and industry access to our state-of-the-art facilities enabling them to fulfil their research goals across a wide variety of scientific disciplines. This report illustrates the fantastic benefits the facility has delivered and brilliant science being achieved by our 14,000-strong user community, who are tackling some of the most challenging scientific questions of the 21st century.  We are so grateful to our funding agencies UKRI’s STFC and the Wellcome for their trust and ongoing support.Chief Executive of Diamond, Professor Andrew Harrison OBE

Read more on the Diamond website

Image: Aerial image of Diamond Light Source

Credit: Diamond Light Source

X-rays get a grip on why erucamide slips

X-Ray Reflectivity measurements offer insights into a slippery industrial additive

Slip additives have a wide range of industrial uses, finding their way into everything from lubricants to healthcare products. Fatty acid amides have been used as slip additives since the 1960s, and erucamide is widely used in polymer manufacturing. Research into erucamide migration and distribution and its nanomechanical properties has shown that the assembly and performance of the slip-additive surface depend on concentration and application method, as well as the substrate surface chemistry. However, questions remain regarding the nanostructure of organised erucamide surface layers, including the molecular orientation of the outermost erucamide layer. In work recently published in the Journal of Colloid and Interface Science, a team of researchers from the University of Bristol and Procter & Gamble used a combination of techniques to investigate the erucamide nanostructure formed in a model system. Their findings will allow the use of rigorous scientific methods in real-world scenarios. 

Essential erucamide

Manufacturers use slip additives to modify the surface structure of a wide range of materials, reducing friction without compromising the material’s other properties (e.g. modulus). Slip additives are included in everything from food packaging and textiles, dyes and lubricants, to hygiene products such as nappies.

Read on the Diamond website

Image:Multiscale characterisation of polypropylene (PP) fibre vs polypropylene fibre + 1.5 % erucamide: (A) Optical microscopy, (B) Scanning Electron Microscopy, (C) Atomic Force Microscopy (height image)

X-ray Ptychography performed for first time at small-scale Laboratory Source

In recent years, X-ray ptychography has revolutionised nanoscale phase contrast imaging at large-scale synchrotron sources.  The technique produces quantitative phase images with the highest possible spatial resolutions (10’s nm) – going well beyond the conventional limitations of the available X-ray optics – and has wide reaching applications across the physical and life sciences. A paper published in Physical Review Letters on 12 May 2021, reveals that an international collaboration of scientists has demonstrated for the first time how the technique of high-resolution phase contrast diffraction imaging can be performed with small-scale laboratory sources.

The team from Diamond, Ghent University, University of Sheffield, and University College London conducted an experiment with a compact liquid metal-jet (LMJ) X-ray source. Laboratory X-ray sources have significantly lower levels of brilliance but currently provide the X-ray synchrotron user community with access to micro-CT, where they can gain a great deal of experience and produce preliminary data, at their home institutions. Until now, no such equivalent has existed for nano-scale imaging through coherent diffraction imaging and ptychography. The team’s paper outlines such an experiment and the first proof of concept for far field X-ray ptychography performed using an X-ray laboratory source. 

Read more on the Diamond website

Image: A reduced selection of the four-dimensional intensity data recorded during the experiment.

Credit: Diamond Light Source Ltd.

Giving rice new weapons to fight rice blast disease

Understanding how a fungal pathogen interacts with rice cells could help us engineer new defences 

Rice is one of the world’s most important agricultural crops, with 741.5 million tonnes produced in 2014. A large proportion of the global population relies on rice as a staple food, particularly in Asia and Africa. However, harvests are threatened by rice blast disease, caused by the fungus Magnaporthe oryzae, which destroys enough rice to feed around 200 million people every year. Rice and the rice blast fungus are involved in a co-evolutionary arms race, fighting for the upper hand. As the fungus relies on effector proteins to help it infect and reproduce within rice plants, rice has evolved immune receptors that allow it to detect and prevent the spread of the fungus. However, the rice blast fungus has evolved stealthy effector proteins that remain undetected by the rice immune system but can still promote disease. In work recently published in the Journal of Biological Chemistry, an international team of scientists has investigated how one stealthy effector protein might maintain its disease-promoting activity but evade immune detection. This research has an ultimate aim of engineering a receptor that would allow rice plants to better defend themselves. 

A pain in the paddy field

We’re familiar with images of the rice paddies of Asia, but this impressive sight represents an irresistible target for the rice blast fungus, Magnaporthe oryzae. Unable to run away from pests and pathogens, plants have evolved immune systems to detect and defend against attack. However, huge swathes planted with the same variety creates an evolutionary pressure for pests and pathogens; a feast is at hand if they can evade those defences. 

One way that pathogens try and gain an advantage is through the use of effector proteins. These proteins can suppress the plant’s immune system and manipulate the plant’s own systems to help the pathogen infect and replicate. However, the mechanisms they employ to do so are not fully understood.  

In collaboration with scientists from Japan and Thailand, researchers at the UK’s John Innes Centre and The Sainsbury Laboratory have been investigating the interaction between rice plants and the rice blast fungus, with the ultimate goal of engineering new genetic resources that will help rice fight this damaging disease.

Read more on the Diamond website

Image: Rice fields in Asia