Category: Diamond Light Source

Cosmic dust could have sparked life on Earth

Cosmic dust could have sparked life on Earth

New research has found that amino acids, the building blocks of life, may have travelled to Earth on interstellar dust grains, potentially helping kickstart biology as we know it.

In a recent study published in the Monthly Notices of the Royal Astronomical Society, Stephen Thompson, I11’s principal beamline scientist, and Sarah Day, I11 beamline scientist, explored how amino acids like glycine and alanine could survive the harsh conditions of space and make their way to Earth embedded in cosmic dust.  

Amino acids are the molecular foundations of proteins and enzymes, which drive every biological process in living organisms. While scientists have long debated whether these molecules formed on Earth or arrived from space, this new study offers compelling evidence that cosmic dust may have played a crucial role in delivering them. The team synthesised tiny particles of amorphous magnesium silicate, a major component of cosmic dust, and deposited amino acids – glycine, alanine, glutamic acid, and aspartic acid – onto them. Using infrared spectroscopy and synchrotron X-ray powder diffraction, they then examined how these molecules behaved when the silicate particles were heated, simulating the warming that occurs as dust grains travelled through the early solar system. 

They found that only glycine and alanine successfully adhered to the silicate particles. These amino acids formed crystalline structures and in the case of alanine remained stable at temperatures well above its melting point. The study also found that the two mirror-image forms of alanine (L- and D-alanine) behaved differently under heating, with L-alanine showing more reactivity than its D-form. Glycine, on the other hand, was lost from the silicate at temperatures lower than its pure decomposition point, indicating that it detached from the grain surface rather than breaking down.  

The team prepared two batches of amorphous silicate and subjected one batch to heat treatment prior to depositing the amino acids. This was to remove hydrogen atoms from the silicate surface, producing two silicates with differing surface properties, which were also found to influence the temperatures at which the amino acids were lost.    

These subtle differences may have had profound implications for the types of molecules that seeded life on Earth. 

Read more on the Diamond website

Image: Stephen Thompson, I11’s principal beamline scientist, and Sarah Day, I11 beamline scientist, working on their cosmic dust research

Credit: Diamond Light Source   

Open science yields broad-spectrum coronavirus antiviral

Open science yields broad-spectrum coronavirus antiviral

A new broad-spectrum coronavirus antiviral, ASAP-0017445, has been nominated as a pre-clinical drug candidate by the Drugs for Neglected Diseases initiative (DNDi).

The candidate is the first coronavirus antiviral developed through crowdsourcing and open-science, and the first with its origins in artificial intelligence (AI). The candidate is a result of research from the COVID Moonshot initiative which originated at Diamond Light Source. 

It is a main protease inhibitor that shows promising activity against SARS-Cov2 and other viruses of the same family, including other viruses of pandemic potential such as MERSCoV – hence its qualification as broad-spectrum. The compound was designed and developed by the open-science research initiative COVID Moonshot and its sister organisation, the AI-driven Structure-enabled Antiviral Platform (ASAP) consortium. 

“Our goal is to deliver an effective and affordable antiviral medicine that would be accessible to everyone if and when the next coronavirus pandemic strikes,” said Annette von Delft, Head of Anti-Infectives at the Centre of Medicines Discovery, University of Oxford, and partner of the Moonshot initiative. 

The COVID Moonshot was a spontaneous global collaboration that started in March 2020, triggered by data from Diamond’s XChem platform for fragment screening. Researchers around the world submitted more than 18,000 molecule designs to inhibit the main protease of SARS-CoV-2. 

The detailed structures were made openly available, ensuring that every stage of the discovery process could be built upon by the global research community. This commitment to transparency and open data laid the foundation for the optimisation of ASAP-0017445. 

Diamond’s contribution highlights the importance of advanced research infrastructure in accelerating drug discovery. By combining crystallography, computational modelling, and global crowdsourced design, the Moonshot demonstrated how open collaboration can deliver a drug candidate intended to be direct-to-generic and globally accessible. 

The structure of ASAP-0017445 was publicly disclosed in March 2025. All the data generated during its development, including the structure data of the more than 2,000 compounds submitted during the crowdsourcing phase, are publicly available. Other researchers can build on this unprecedented dataset for drug discovery for their own research.

Read more on Diamond website

Synchrotron science uncovers the origins of lizards

Synchrotron science uncovers the origins of lizards

A tiny fossil from Devon has shed new light on the origins of lizards, thanks to advanced synchrotron imaging carried out at Diamond Light Source and the European Synchrotron Radiation Facility (ESRF).

Researchers from the University of Bristol have identified the fossil as the oldest known member of the lizard lineage, dating back 242 million years to the Middle Triassic, just before the rise of the dinosaurs. Their findings, published in Nature, reveal unexpected details about the early evolution of lizards, snakes, and their relative, the tuatara, a group collectively known as the Lepidosauria.

Lepidosaurs are today the most successful group of land vertebrates, with more than 12,000 living species. Scientists long assumed their earliest ancestors would share key features of modern lizards and snakes, such as hinged skulls and palatal teeth. However, the new fossil challenges those assumptions.

“The new fossil shows almost none of what we expected,” said Dan Marke, who led the project as part of his studies for the MSc in Palaeobiology at Bristol. “It has no teeth on the palate, and no sign of any hinging. It does though have the open temporal bar, so one out of three. Not only this but it possesses some spectacularly large teeth compared to its closest relatives.”

Professor Genoveva Burca, Principal Beamline Scientist of I12-JEEP, said: “We are pleased to contribute to the scientific understanding of this sample. The unique capabilities of the the beamline, including its large beam size and high energy, combined with our expertise in advanced imaging methods, underscore the crucial role that synchrotron light sources like Diamond play in advancing palaeontological research.”

Because the specimen’s skull measures only 1.5 cm, traditional CT scans could not resolve the fine details. To overcome this, the team turned to high-energy synchrotron X-ray imaging. Using two powerful beamlines, I12 at Diamond Light Source and one at ESRF, the researchers were able to produce exceptionally detailed 3D models of the skull without damaging the delicate fossil.

One of I12’s scientists, and co-author of the paper, Alexander Liptak, explained: “I12 was the only beamline at Diamond suitable for this experiment. The study required a large beam size and high beam energy to accommodate both the fossil’s dimensions and attenuation, as well as the necessary contrasting medium introduced to account for the fossil’s high aspect ratio. Furthermore, the high photon flux available at I12 enabled us to virtually ‘inspect the sample’ by performing rapid exploratory XCT acquisitions and partial reconstructions, which were used to directly inform the necessary positioning and resolution requirements for subsequent scans.”

Read more on Diamond website

UK and France ministers back AI drug discovery at Diamond

UK and France ministers back AI drug discovery at Diamond

The UK’s Parliamentary Under-Secretary of State at the Department of Science, Innovation and Technology, Feryal Clark, visited Diamond to gain insights into the groundbreaking work planned by the OpenBind consortium.  An ambitious initiative that aims to revolutionise drug discovery through artificial intelligence. 

Ms Clark, who is the Under-Secretary of State for AI and Digital Government, was accompanied by Clara Chappaz, France’s minister delegate for artificial intelligence and digital affairs. 

OpenBind, which recently secured £8 million in anchor funding from DSIT’s Sovereign AI Unit, will generate the world’s largest dataset on drug-protein interaction – twenty times larger than any previous effort in the field. This data will be used to train next-generation AI models capable of identifying new drugs faster and more affordably, promising to significantly reduce development costs.  

Ms Clark and Ms Chappaz toured the facility with Diamond’s CEO Gianluigi Botton to observe key research instruments. The ministers visited the I04-1 beamline, which will be integral to OpenBind’s ambitions. 

It was great to visit Diamond Light Source with our French partners, to see some of the work making the UK a global hub for AI-driven drug discovery. The OpenBind consortium is a brilliant example of how world-leading UK capabilities are unlocking new AI models that can identify new treatments, faster.

Backed by our Sovereign AI Unit, this cutting-edge work, applying AI tech to biosciences, has huge potential to unlock new avenues to attract international investment and help rebuild our NHS. This is critical work in support of our Plan for Change.

Feryal Clark, Under-Secretary of State for AI and Digital Government

OpenBind exemplifies Diamond’s integral role in harnessing home-grown AI expertise to drive global innovation and impact. By combining Diamond’s world-class capabilities with advanced AI technologies, we are not only improving drug development but also delivering on the UK’s technological ambitions.

Diamond CEO Gianluigi Botton

The OpenBind consortium represents the ambitions laid out in the government’s AI Opportunities Action Plan, which calls for investment in AI to drive economic growth, transform public services and position the UK as a global leader in responsible AI innovation. OpenBind’s collaborative approach, bringing together academia and internal expertise, also reflects the importance of EU partnerships, ensuring that scientific breakthroughs are shared across borders to tackle global challenges in health and sustainability. 

Read more on Diamond website

Image: Diamond Head of Industrial Liaison Elizabeth Shotton; French Minister Delegate for artificial intelligence and digital affairs Clara Chappaz; Under-Secretary of State for AI and Digital Government Feryal Clark; and Diamond CEO Gianluigi Botton.

Visualising soil aggregates: shedding light on soil structure

Visualising soil aggregates: shedding light on soil structure

xperiments at I14 beamline reveals how organic matter binds soil

Have you ever wondered how the soil you walk on was formed? Soil is a mixture of organic matter, minerals, gases, water and organisms that support the life of plants and soil organisms. Soil is an essential resource for, among other things, food production, water filtration, nutrient cycling and carbon sequestration. Healthy soil is the cornerstone of sustainable agriculture and climate resilience, and its physical structure, especially the formation of aggregates, is key to its function. Soil aggregates are clusters of soil particles that bind together, influenced by biological, chemical, and physical processes. They affect water retention, aeration, root penetration, and microbial habitats. Understanding how these structures form is crucial for improving soil health and productivity, but their development at the microscale remains poorly understood. 

In an article recently published in the journal Soil Biology and Biochemistry, researchers from Lund University used advanced imaging at Diamond Light Source to track organic matter within forming soil aggregates. By labelling plant litter with rare earth elements and tracing their distribution using synchrotron radiation-based nano X-ray Fluorescence (nano-XRF) at the beamline I14, they visualised how organic matter physically embeds into soil particles. 

Understanding soil better through high-resolution visualisation

Before this study, researchers had observed that organic matter inputs, such as plant litter, can stimulate aggregate formation. However, the exact mechanisms, particularly the role of particulate organic matter (POM) and microbial activity in initiating and stabilising aggregates, were largely speculative. The field lacked detailed, spatially resolved analyses that could directly visualise how inputs become integrated into soil microstructures. 

Historically, studies relied on bulk chemical analysis and low-resolution imaging to assess organic matter in soil. However, these methods lacked the spatial precision to identify where and how litter becomes part of the aggregate matrix. As a result, researchers couldn’t fully determine whether physical incorporation, microbial binding, or chemical interactions were the main drivers. 

This research addressed that gap using nano-XRF imaging, allowing scientists to distinguish between particulate litter, mineral particles, and microbial hotspots in forming aggregates. The central scientific question was: what mechanisms underlie the physical integration of organic matter into soil structure, and how do different types of litter influence this process? 

This insight is crucial for land management and soil carbon storage strategies. By pinpointing the types of organic inputs that most effectively promote aggregation, the research provides a pathway to improving soil function and resilience. 

The role of Diamond synchrotron techniques in this study

The use of nano-XRF at Diamond’s I14 beamline enabled the team to track rare earth-labelled litter with high spatial resolution. This technique allowed for precise visualisation of micron-scale structures within soil aggregates, something traditional imaging could not achieve. The beamline’s capabilities in elemental mapping and chemical speciation were essential for distinguishing between organic particles and mineral matter. 

The imaging revealed that soil aggregates often formed around organic matter particles, with straw being embedded into the larger ones (>250 μm) to a higher extent. A known fungal preference for straw suggests their contribution to the process via physical binding of particles within their hyphal networks. Surprisingly, while microbial activity is typically assumed to be a major driver, the study found that microbial community composition had overall limited influence over the short duration (seven weeks) of the incubation period of the experiments. 

Read more on Diamond website

Image: Overlay image of Sm (blue) and Nd (yellow) binary nXRF intensity maps of a small microaggregate; magenta colour indicates area where Sm and Nd overlap

Diamond scientists win RSC prize for chemistry-aware AI software

Diamond scientists win RSC prize for chemistry-aware AI software

Four scientists from Diamond have been awarded the Materials Chemistry Horizon Prize for their work on accelerating data-driven chemical materials discovery.

The winning AI for Materials team includes Diamond’s Phil Chater, Francesco Carla, Chris Nicklin, and Jonathan Rawle.

The prize honours their exceptional work in developing chemistry-aware artificial intelligence software. The work includes applying this advanced technology to data-driven materials discovery and providing open-source materials databases and language models for the global scientific community.

The team from Diamond were very pleased to contribute to this project that involved a large multinational team. It has been a great collaborative effort to develop the use of artificial intelligence in materials discovery.

Chris Nicklin, Diamond’s Deputy Director of Physical Sciences

Diamond’s four winners were part of a team that includes AI-experts from Cambridge and US supercomputing specialists at Argonne National Laboratory, supported by researchers from around the globe. This included scientists from ISIS Neutron and Muon Source and the Research Complex at Harwell.

The team developed ChemDataExtractor, the first chemistry-aware text mining tool. The materials-domain-specific language software provides an interactive way for scientists to ask questions, similar to the ChatGPT model.

They were able to demonstrate data-driven materials discovery in less than one year, vastly reducing the average 20 year timeframe it usually takes industry to discover new material for a given application.

The resulting high-quality experimental databases and chemistry-specific language models will now help guide scientific decisions and speed up research. To mark their achievements, the team will receive a trophy, and each team member will be presented with a special individual token. Additionally, their remarkable work will be showcased in a special video.

Rea more on Diamond website

Diamond will host a pioneering AI-driven drug discovery consortium

Diamond will host a pioneering AI-driven drug discovery consortium

Diamond will be the base for OpenBind, an AI-driven drug discovery centre which will make the UK a world-leader in drug innovation and advancement.

With its unparalleled XChem facilities, Diamond will be a global hub for AI-driven drug discovery. This will lead to the prospect of tackling previously untreatable diseases and dramatically reducing the cost of drug discovery and development. The project is backed by up to £8 million of investment from DSIT’s newly established Sovereign AI unit, a key driver in the government’s AI Opportunities Action Plan.

The consortium will close critical data gaps by using new AI models to find potential new drugs and help create better treatments for diseases. It will also help scientists use engineering biology to solve bigger problems, like making enzymes that can break down plastic waste.

The main aim is to create the world’s largest collection of data on how drugs interact with proteins, the building blocks of the body. Using automated chemistry and high-throughput X-ray crystallography, the consortium will generate more than 500,000 protein-ligand structures over a period of five years. This is twenty times greater than anything collected in the last 50 years.

OpenBind will offer a core dataset that will drive progress across scientific and technological areas, including predicting molecular structures, designing new molecules and improving research workflows. It will work in tandem with other new methods in order to reduce trial-and-error experimentation, guide better decision-making, and support more efficient exploration of chemical possibilities.

At Diamond Light Source, a joint venture between the UK government through STFC and the Wellcome Trust, we are proud to be at the forefront of the UK’s ambition to lead the world in AI-driven drug discovery. OpenBind represents an exciting step forward in harnessing our unique capabilities to generate the high-quality data that AI needs to revolutionise healthcare, helping to cement the UK’s position as a global hub for bioscience innovation.

Professor Gianluigi Botton, CEO of Diamond Light Source

The consortium will be led by some of the world’s leading scientific minds including Professor Frank von Delft, principal scientist of the macromolecular crystallography I04-1 beamline and the XChem facility at Diamond, as well as the University of Oxford’s Professor Charlotte Deane and Nobel laureate David Baker, head of the Institute for Protein Design at the University of Washington.

Read more on Diamond website

Image: Professor Frank von Delft, Diamond’s principal scientist of the MX I04-1 beamline and the XChem facility

Unraveling iron uptake and magnetosome formation in magnetospirillum gryphiswaldense

Unraveling iron uptake and magnetosome formation in magnetospirillum gryphiswaldense

Diamond Light Source sheds light on bacterial biomineralisation processes

Iron plays several essential roles in bacteria, making it a crucial element for their survival and function. In magnetotactic bacteria like Magnetospirillum gryphiswaldense, iron plays a central role in the formation of magnetosomes. These peculiar bacteria possess the capability to orient themselves along the Earth’s magnetic field lines, thanks to the presence of a very specific type of intracellular magnetic nanoparticles called magnetosomes. Magnetosomes are mainly composed of magnetite crystals (Fe3O4) enveloped in a lipidic membrane. Some mechanisms such as the internalisation and the transformation of iron into magnetite crystals are still poorly understood. In an article recently published in ACS Applied Materials & Interfaces, a team of researchers from Aston University investigated the formation of these magnetosomes in bacteria by finely tuning the concentration of oxygen and iron. They performed CryoSIM and CryoSXT experiments on the B24 beamline. The team were also the first to exploit the recent development of the beamline to measure X-ray absorption data at the Iron L3 edge to aid visualisation of the magnetsomes.

Advancing understanding of bacterial magnetosome formation

Magnetosome formation in magnetotactic bacteria is a complex process influenced by environmental factors such as iron concentration and oxygen levels. Prior studies provided foundational knowledge but lacked the resolution to observe these processes at the single-cell level under near-native conditions. Given the small size of magnetosomes, which can range from 30 nm to 120 nm across different species, electron microscopy is one of the most common used imaging techniques. However, this approach does not enable simultaneous tracking of intracellular iron content alongside magnetosome content to understand better how the biomineralisation process works. This research aimed to bridge that gap by employing an integrated approach combining correlative light and X-ray microscopy with other analytical techniques.

Firstly, the data obtained from these other analytical techniques suggested a potential correlation between the intracellular iron pool and magnetosome content. Specifically, increased iron availability under microaerobic conditions appeared to result in longer magnetosome chains and higher intracellular iron concentrations. To further investigate and validate this hypothesis at the single-cell level, the researchers conducted experiments at the B24 beamline at Diamond.

Utilising Diamond Light Source for advanced imaging

Cryo-SXT is a powerful technique used to observe the internal structure of biological samples in a near-native state. This technique uses soft-X rays to obtain three-dimensional (3D) tomograms of biological specimens with a resolution of up to 25 nm, without the need for traditional sample preparation methods that could damage cellular structures (such as drying, chemical fixation, staining). On B24, the team was able to observe internal compartments, including magnetosomes, using the preferential absorption of carbon atoms in the cell. With cryoSIM, they stained the bacteria with PG-SK, a green fluorophore that reacts with the intracellular iron. The strength of the B24 beamline is that scientists were able to analyse the same region of interest in the same samples with both CryoSIM and CryoSXT and correlate the data.

This approach provided compelling evidence of a correlation between the intracellular iron concentration and the number of magnetosomes. Another advantage of using soft X-ray microscopy at B24 is the ability to adjust the X-ray energy to the iron absorption edge. As iron atoms strongly absorb X-rays at this energy, it facilitates the observation of magnetosomes within the bacteria. By modifying the iron concentration during bacterial growth, the researchers demonstrated that these bacteria can tolerate high extracellular iron concentrations. They also identified an iron threshold beyond which increasing the extracellular iron concentration no longer leads to additional iron uptake or an increase in magnetosome production.

Read more on Diamond website

A Greener Route to Gold Nanoparticles

A Greener Route to Gold Nanoparticles

High-resolution scanning transmission electron microscopy confirms a new, mild approach to metal nanoparticle synthesis

Gold nanoparticles (NPs) are used in a variety of applications including catalysis, drug delivery, biosensing, and electronics. Traditional methods for producing gold NPs often involve harsh conditions and tend to produce larger NPs (10-200 nm). Smaller gold NPs (less than 10 nm) are more desirable for catalysis, because their higher surface area to volume ratio offers a higher number of catalytically active surface sites, and hence greater reactivity. There is, therefore, a need to develop more sustainable methods of synthesising metal nanoparticles that allow precise control over their size and shape. However, bio-based synthesis methods using plant extracts or microorganisms often result in poor uniformity. In addition, there is a lack of sustainable methods for synthesising core-shell NPs, which are composed of two or more materials. In work recently published in Angewandte Chemie, researchers from the University of Oxford demonstrated a mild synthesis method that produced NPs with high uniformity of size and shape. Using high-resolution scanning transmission electron microscopy (HR-STEM) at the electron Physical Science Imaging Centre (ePSIC), they showed that the synthesis could also form core-shell Au@Pt nanoparticles. Their results suggest that this approach could be used to develop a new type of self-synthesised chemo-biocatalyst with wide-ranging applications in biotechnology.

Overcoming challenges in green nanoparticle synthesis

Metal nanoparticles have a wide variety of uses, from drug delivery to catalysis. Smaller NPs are more desirable for catalysis due to their greater reactivity, and gold is often combined with platinum group metals in core-shell NPs to improve reactivity and stability. As traditional synthesis methods rely on harmful chemicals or high temperatures, there is a need to develop more sustainable processes. However, bio-based strategies using plant extracts or micro-organisms struggle to produce NPs with the high uniformity required.

In this work, a research team from the University of Oxford developed a more sustainable method for synthesising metal nanoparticles using an isolated enzyme, NAD+ reductase (NRase), to achieve better control over size, shape, and catalytic activity.

They used NRase to reduce gold (Au) salts, in a process that involves the oxidation of NADH at the enzyme’s active site, which releases electrons used for the reduction of the metal salts. The new process resulted in the formation of highly uniform, spherical gold nanoparticles. By varying the concentration of NRase, the researchers were able to precisely control the size of the resulting nanoparticles; higher concentrations of NRase led to smaller nanoparticles, indicating that the enzyme acts as a template for nanoparticle formation.

The team was also able to use the process to synthesise core-shell NPs. After forming a gold NP, they found that adding platinum salts and more NADH resulted in the deposition of a platinum (Pt) shell over the gold core.

HR-STEM confirms nanoparticle structures

The team used several imaging techniques to characterise the synthesised nanoparticles, including UV and visible light spectroscopy to monitor the formation of nanoparticles and to estimate their average diameter and transmission electron microscopy (TEM) to directly observe the size, shape, and structure of the nanoparticles. Using HR-STEM at ePSIC allowed them to confirm the core-shell structure of Au@Pt NPs, with the results showing a higher ratio of platinum in the outer layers and gold (Au) in the centre.

Christopher Allen, Principal Electron Microscopist at ePSIC commented:

At ePSIC, the ability to simultaneously acquire atomic resolution images – which tells us where the atoms are – with energy dispersive X-ray spectroscopy – which tells us what the atoms are – is an incredibly powerful tool. This enables us to develop a fundamental understanding of the chemistry that is occurring during a catalytic process, which in turn can help us to develop increasingly efficient catalyst materials. The work by Professor Vincent’s group at ePSIC is a great example of how information about atomic structure can enable us to understand the macroscopic properties of materials.

Read more on Diamond website

Unlocking the secrets of hafnia: a new era in ferroelectric materials

Unlocking the secrets of hafnia: a new era in ferroelectric materials

Depth-resolved X-ray Photoelectron Spectroscopy probes the link between polarisation and electrochemistry

Ferroelectric materials exhibit a unique property called spontaneous polarisation. Their built-in electric dipole moment can be switched between different directions by applying an external electric field. This makes them incredibly useful for a wide range of applications, including memory storage devices, sensors, and energy harvesters. The discovery of ferroelectricity in nanoscale hafnia-based films has spurred extensive research to understand its origin and unlock its full potential. Hafnia displays unusual behaviour in that its ferroelectricity becomes stronger as the material gets thinner, and one theory suggests that the electrochemical state within the hafnia film is directly linked to its polarisation and responsible for the unique size-dependent properties.

In work recently published in Advanced Materials, researchers from the University of Cambridge used depth-resolved X-ray Photoelectron Spectroscopy (XPS) at Diamond’s I09 beamline to investigate the intricate relationship between polarisation and electrochemical changes in hafnia-based ferroelectrics. The results suggest that the electrochemical state is not directly linked to polarisation, and that certain dopants can suppress the electrochemical changes that cause degradation without sacrificing polarisation, opening up exciting possibilities for engineering more robust and reliable ferroelectric devices.

Surprising findings in nanoscale hafnia films

The research team focused on two specific compositions, Hf0.5Zr0.5O2 (HZO) and Hf0.88La0.04Ta0.08O2(HLTO), both in the form of single-phase epitaxial films. These films were chosen to minimise the influence of grain boundaries and other structural complexities that could complicate the analysis. The first step was to meticulously characterise the structure and ferroelectric properties of the HLTO and HZO films using a combination of techniques. They used X-ray Diffraction (XRD) to determine the crystallographic phase and orientation of the films, Piezoresponse Force Spectroscopy (PFS) and Microscopy (PFM) to confirm the presence of ferroelectricity and visualise the domain structure and Positive-Up Negative-Down (PUND) measurements to measure the remnant polarisation and coercive field, key parameters describing the ferroelectric behaviour.

These initial characterisations confirmed the presence of the desired ferroelectric phases in both HLTO and HZO and identified 24 areas on the samples, two sets of each specific polarisation state (P-up, P-down, or as-grown), to analyse using depth-resolved XPS.

Dr Nives Strkalj explained:

Our hafnia samples were intended to be very similar in terms of polarisation, but we were expecting to see changes in their electrochemistry when we used an electric field to change the polarisation. We opted for the I09 beamline because it’s a unique setting where you can change between X-rays that probe deep and shallow with just the click of a button. Usually, if you want to probe depth, you have to realign the incidence angle, then you have to realign the detector, and it’s very time consuming. We had to check many areas of our samples, areas which were P-up, or which were P-down, and on I09 we can get depth probing very quickly.

During the XPS experiments, the researchers discovered a surprising difference in the electrochemical behaviour between HLTO and HZO. In the P-up state, HLTO showed an increase in non-lattice oxygen (NL-O) primarily at the surface, suggesting that the electric field was driving oxygen species from the atmosphere onto the film. In contrast, HZO displayed an increase in NL-O distributed throughout the bulk of the film, accompanied by reduction of the Hf and Zr cations. These findings suggest that the polarisation state is not solely responsible for the changes in oxygen electrochemistry in these materials. Instead, the electric field used to switch the polarisation plays a crucial role.

Read more on Diamond website

Breakthrough in next-generation polio vaccines

Breakthrough in next-generation polio vaccines

A more affordable, lower-risk vaccine could soon be possible following research conducted at Diamond’s electron Bio-Imaging Centre (eBIC).

Scientists have made significant progress in developing a more cost-effective and safer polio vaccine, something which is essential for the global effort to eliminate the disease. Polioviruses mainly affect children under five years of age, with some infections leading to irreversible paralysis and sometimes death.  

For the last three decades, the World Health Organization, which funded the study, has been focused on the worldwide eradication of polio. Since 1988, poliovirus cases have decreased by 99% and the possibility of eliminating this disease is on the horizon. The prospect of a new type of vaccine could play a significant part in this endeavour.

The research project looked at using virus-like particles (VLPs). These particles imitate the outer protein structure of the poliovirus but are hollow inside and do not contain any viral genetic material. This eliminates the risk of infection while still triggering an immune response. 

Researchers from the University of Leeds have been exploring how different types of cells – yeast, mammalian and plant cells – can be used to produce VLPs. Their findings, recently published in Nature, indicate that VLPs generated in yeast and insect cells can perform equally or better than the currently used inactivated polio vaccine (IPV).  

Peijun Zhang, director of eBIC, said:

Cryo-EM at eBIC enables scientists to determine the detailed 3D structure of VLPs, revealing how they resemble real viruses in shape and protein arrangement. This helps researchers optimise the design of VLP-based vaccines to ensure they trigger a strong immune response while remaining non-infectious.

The current polio vaccine (IPV) is relatively expensive to use as it requires a high level of biocontainment to minimise the risk of leaks of the live polio virus, which could lead to outbreaks. In contrast, the VLP simulated particles are non-infectious, therefore removing the need for bio-safety protocols.   

Professor Nicola Stonehouse, of the University of Leeds School of Molecular and Cellular Biology and one of the senior authors on the paper, said: “Any vaccine is only as effective as the number of children that it reaches. The key is to make vaccines universally accessible, as all children have a right to be protected from diseases such as polio, no matter where they live. VLPs would significantly contribute to vaccine equity.”

The plan to eradicate polio

The oral polio vaccine (OPV) contains a weakened vaccine-virus and its continued use could hinder the complete eradication of the disease. Once all strains of wild poliovirus strains are eradicated, the use of OPV will be phased out. This is because the weakened form of the virus in the OPV can sometimes mutate and cause variant forms. When the use of the OPV stops, the IPV will be the only available vaccine. However, its expensive manufacturing procedure make it unaffordable for lower-income countries, possibly leading to a reduction in vaccination rates.  

The virus-like particle (VLP) vaccines are the promising alternative, as with no viral genetic material, they are non-infectious and safer than traditional vaccines. They can also be engineered to be more stable, which maintains their effectiveness during storage or transportation. 

This could eventually lead to a more equitable access to vaccination, ensuring that countries that do not have suitable infrastructure can safely store and distribute the vaccine.  

VLP vaccines have already been successfully used for other diseases, like hepatitis B and human papillomavirus (HPV), and researchers have been working for over a decade to successfully apply this technology to help eradicate polio.  

The international research collaboration includes researchers from the University of Oxford, the Medicines and Healthcare products Regulatory Agency (MHRA), the John Innes Centre, the Pirbright Institute, the University of Florida and the University of Reading. All of the cryo-EM data was collected at eBIC.  

Read more on Diamond website

Targeted Destruction of Disease-Related Proteins

Targeted Destruction of Disease-Related Proteins

A new protein construct helps scientists study drugs that break down protein targets.

While most conventional drugs work by inhibiting proteins, not all proteins are easy to block in this fashion. Drug developers are investigating new classes of drugs that mark proteins for degradation in the cell. A large, barrel-shaped structure called the proteasome drives this breakdown process, and a protein called Cereblon behaves as an usher, delivering proteins to the proteasome for destruction. Some drugs act as “molecular glue”, sticking to Cereblon and altering its structure so that it binds to target proteins. Other drugs called proteolysis targeting chimeras (PROTACs) bind to target proteins and Cereblon, bridging the two together. Thus, an in-depth understanding of Cereblon’s morphology is crucial for drug investigations. However, scientists have struggled to determine high-resolution structures of this protein in the past due to complications with its synthesis and stability. David Zollman, a structural biologist and drug developer at the University of Dundee, and his colleagues developed a highly stable, easily purified Cereblon variant. Collecting X-ray crystallography data at the Diamond Light Source beamlines I04 and I24, they demonstrated that the structure of their Cereblon variant matched ones previously collected by other groups, but the new crystals achieved higher resolution. Cereblon changes shape when bound to different drugs, and the team collected small-angle X-ray scattering (SAXS) data at beamline B21 to study how shapeshifting varies between different drug candidates. Together, these findings reveal that the new Cereblon variant is amenable to structural analysis, which could facilitate future research into this promising class of protein-degrading drugs. 

Most conventional drugs work by inhibiting proteins. The pain-reliever ibuprofen, for example, blocks a bodily enzyme called cyclooxygenase by stoppering its active site and preventing it from producing chemical signals that induce pain. However, Zollman said that researchers have long considered some proteins “undruggable” because they lack active sites that can be targeted by inhibitors. These include proteins that have structural roles rather than enzymatic functions. Taking an alternative approach, scientists are exploring drugs that flag proteins for degradation in the cell by protein shredders called proteasomes. 

The most infamous example is the drug thalidomide, a sedative from the 1950s that pregnant women took to relieve morning sickness but led to birth defects. Today, doctors have repurposed thalidomide to treat multiple myeloma, and researchers have developed other drug candidates, like lenalidomide and mezigdomide to treat other cancers. Currently, there are over 40 drugs related to the degradation pathway in cells undergoing clinical trials. Many of them work by recruiting transcription factors to Cereblon and targeting them for destruction, thereby preventing the expression of an array of genes.  

Research into these drugs has been held back by a lack of structural insight into Cereblon. Previously, scientists could only purify Cereblon coupled with an adapter protein called Damage Specific DNA Binding Protein 1 (DDB1), resulting in an unwieldy complex. Scientists also struggled to produce high yields of the protein, and they could only prepare it in insect cell expression systems. When scientists managed to crystallize the protein, they found it was unstable, hampering efforts to collect high-resolution structural data. Most experiments determined the structure to a resolution of 3 Ångströms (Å) or worse. Dr Zollman said:

It’s expensive to produce, hard to get in large quantities, and then when you do have it, it’s quite poorly behaved.

What scientists needed was a stable version of Cereblon that was easy to purify in the absence of DDB1. Dr Zollman commented:

We have cut out the part of Cereblon that binds to DDB1, and because of that, we are able to produce it stably from E. coli on its own.

E. coli are the go-to bacteria for producing proteins for purification, making it easier to achieve high yields for scientific studies. 

Besides omitting the DDB1-binding domain, Zollman’s team designed 15 versions of Cereblon, some of which carried unique sets of mutations that swap out one amino acid for another in different places. They introduced these mutations to stabilize the proteins, and they discovered that version 8, complete with 12 mutations, proved most stable. “We can get it at a much higher yield, it’s much cheaper to produce, it’s much easier to produce, and then the complex does crystallize a lot better.” Zollman said version 8 is a “middle ground” between full-length Cereblon and other truncated versions trialled previously, so his team renamed it Cereblonmidi.  

Next, they had to put their crystallised Cereblonmidi to the test at the Diamond Light Source. Zollman said the protein formed small crystals, and the microfocus beams at beamlines I04 and I24 enabled his team to collect high-quality data from samples of this size. 

Read more on Diamond website

Uncovering ancient text from the Oxford Herculaneum scroll

Uncovering ancient text from the Oxford Herculaneum scroll

In July 2024, Diamond’s powerful light enabled a team from the nearby Bodleian Libraries to scan a 2,000-year-old Herculaneum scroll. The scroll, one of three housed at the libraries, was studied on the I12 beamline and the collected X-ray data has played a crucial role in deciphering the text of this ancient artefact. 

By scanning the scroll, researchers were able to generate an image of the inside of scroll Pherc. 172, which was buried by the Mount Vesuvius eruption in 79AD. The papyrus texts were flashed seared by the volcanic heat and are thought to be part of the only remaining intact library from the ancient world.  

The scroll was buried and carbonised during the eruption, and previous attempts to open similar scrolls have been largely disastrous. But by using the unique capabilities of Diamond’s beamline, as well as a machine learning programme (AI), researchers have been able to create an “un-rolled” image of the carbonised layers.  

The Oxford scroll is unique due to the chemical composition of its ink, which appears more clearly in Diamond’s X-ray scans. It may be that this scroll’s ink contains a denser contamintant, such as lead, that makes its text more legible than other Herculaneum scrolls.  

The image was made possible by the advanced scanning capabilities of the I12 beamline, a high energy X-ray beamline for imaging, diffraction and scattering, which operates at photon energies of 53-150 keV. 

The scanning and deciphering of the text is part of the Vesuvius Challenge, a global machine learning competition which hopes to recover the contents of the scrolls that were discovered in the 1750s. The majority of the scrolls reside at the Biblioteca Nazionale di Napoli, although several were gifted to the Bodleian Libraries at Oxford University, the British Library and the Insitut de France.

This is not the first time that Diamond has played host to one of these ancient scrolls. In 2019, Professor Brent Seales, who co-founded the Vesuvius Challenge, brought two scrolls and several fragments from the Institut de France. By using Diamond’s scans, along with the pioneering AI software platform his team developed, thousands of characters making up 5% of the scroll, were identified.    

Read more on Diamond website

Image: The Bodleian Libraries Herculaneum scroll.

Simultaneous experiment unlocks new collaborative research potential utilising a joint AI platform

Simultaneous experiment unlocks new collaborative research potential utilising a joint AI platform

Diamond Light Source’s I22 beamline and the ISIS Neutron and Muon Source’s Larmor instrument demonstrate the potential afforded using a cutting-edge technique.

In a groundbreaking experiment, a robotic sample preparation platform, driven by artificial intelligence (AI) was used to undertake simultaneous experiments at both Diamond Light Source, the UK’s National Synchrotron, and the ISIS Neutron and Muon Source, the UK’s National Neutron and Muon Source. While collaborative research between these two science facilities, located on the Harwell campus in South Oxfordshire, is common, this particular experiment has pushed new boundaries with the experiments being performed at the same time on identical robotic set-ups which were in direct communication with each other. 

The simultaneous experiment was driven by two Automated Formulation Laboratories (AFLs), which after a two-year delay with customs, finally made it to the Harwell Campus. They were then installed and operated autonomously on Diamond’s I22 and ISIS’s Larmor small-angle scattering beamlines. The AFLs were produced by research teams from The National Institute of Standards and Technology (NIST), based in Gaithersburg, Maryland, USA, shipped to the Rutherford Appleton Laboratory and then installed at Diamond and ISIS. 

Dr Gregory Smith, from ISIS, said:

We have discussed using the autonomous formulation laboratory for experiments at ISIS for many years, and it was only recently that we considered the idea of running neutron and X-ray measurements in parallel at ISIS and Diamond. Getting one piece of bespoke equipment on site to run an experiment is challenging enough, but it took great effort from many staff here at RAL, from support staff to scientists to engineers, to manage this. I was pleased to finally manage to get the AFLs here and use them as intended, and the exciting results produced by the NIST team justified all this work, resulting in a truly unique experiment.

The experiment investigated paint formulations, making use of small angle scattering to determine properties of the system. The AFL machines, one red and one blue, were linked together across computer networks and worked concurrently, capturing multiple modalities of the formulations synthesised. 

The project had two objectives; the researchers from NIST were testing the AI and robotic elements of the machines, whilst also working on an industrially relevant question – in this case “what is the optimal formulation of a given paint system?”. 

By using both small angle X-ray scattering (SAXS) at the I22 beamline and small angle neutron scattering (SANS) at Larmor, the experiment proved more effective in both the utilisation of beamtime as well as the quality of data collection. SAXS data can be collected more quickly than SANS data, which allowed the experimental team to rule out formulations that weren’t of interest. This allowed a more complete dataset from the significant formulations in a shorter amount of time, as the team could gather insights from the different parts of the system with each technique. Diamond and ISIS offered the unique opportunity for both formulation labs to work in unison at the neutron and X-ray facilities, a situation that is currently only possible in two locations in the world.

Tim Snow, principal software scientist working on Diamond’s I22 beamline, said: 

It is a really good example of both facilities working together to exploit our unique capabilities, acquiring the best data for our users.

The robotic element of the AFL prepares liquid mixtures via pipetting and transfers those mixtures to a measurement cell. Following a SANS or SAXS experiment, the data is analysed by an AI software algorithm. The AI algorithm looks at the collected data to work out what mixture to make next and subsequently what scan to conduct next.  

Read more on Diamond website

Image: The red Automated Formulation Laboratory (AFL) in place on Diamond’s I22 beamline.

Tearing down bacterial membranes with new antibiotics

Tearing down bacterial membranes with new antibiotics

Crystallography reveals how an E. coli drug candidate inhibits an essential enzyme

According to the UN Environment Programme, bacteria resistant to existing antibiotics cause approximately one million deaths each year — a toll expected to soar ten times higher by 2050 if researchers don’t develop alternative therapies. Some bacteria, including some strains of the gut pathogen Escherichia coli or the lung pathogen Klebsiella pneumoniae, are resistant to multiple antibiotics, limiting treatment options. These species belong to a category called ‘Gram-negative’ that do not retain a violet ‘Gram’ dye very well when stained and viewed under the microscope. Members of this group possess two bacterial membranes, the outer of which is studded with fatty carbohydrates called lipopolysaccharides (LPS) that play an essential role in reinforcing the membrane’s integrity. Douglas Huseby, a microbiologist at Uppsala University in Sweden, and his colleagues are designing drug candidates that obstruct LPS synthesis. AstraZeneca previously developed a compound called AZ-1 that could inhibit this pathway but found that it underperformed. After screening other molecules with inhibitory potential, Huseby and his team found one with a similar structure to AZ-1. By merging the two molecules into one, the team developed a potent blocker. X-ray crystallography experiments at Diamond’s I04-1 beamline revealed that the new drug inhibits an essential enzyme by binding to part of the active site. After tweaking the molecule to improve its properties, the team repeated their crystallography work to confirm it bound to the same site on the enzyme. Preclinical tests in mice show a single dose of the drug is safe and effective, underscoring the drug’s encouraging potential. 

No antibiotic is invulnerable to bacterial resistance. Regardless of what bacterial components the drugs target, bacteria evolve defences against every class of the drugs. Now more than ever, clinicians need novel antibiotics that target new microbial features, slowing down the emergence of resistant, untreatable superbugs, but new antibiotics have not completed the journey from the lab to the clinic since the 1970s.

During the mid-20th century, scientists turned to nature to discover antibiotics, but that has become untenable today. “Each new antibiotic you find is about ten times harder to find than the previous one,” Huseby said. Today, scientists focus more attention on designing new antibiotics instead.

Attacking bacteria from the outside

The enzymes that synthesize the fatty sugar lipopolysaccharide (LPS) present an alluring, fresh target. LPS is found on the outer surface of Gram-negative bacteria, which have a thin cell wall and two cell membranes. Several Gram-negative bacteria cause severe infections in humans and have evolved resistance to multiple antibiotics. These include Escherichia coli, a common cause of diarrhoea, and Klebsiella pneumoniae, a tough-to-treat superbug behind pneumonia and meningitis.

LPS is essential in Gram-negative bacteria, as it reinforces the structural integrity of Gram-negative bacteria’s outer membrane, as noted in Mechanism of outer membrane destabilization by global reduction of protein content. Owing to its importance, enzymes involved in its synthesis make good targets for drug design. What’s more, humans lack this synthesis pathway, meaning drugs could theoretically kill bacteria without having collateral effects by disrupting human proteins.

LPS anchors to the outer surface of the bacteria using a fatty molecule called lipid A, and the enzyme that synthesizes this anchor, LpxH, is present in 70% of Gram-negative bacteria, so Huseby and his colleagues wanted to design an antibiotic that could inhibit this enzyme. Since this enzyme is conserved in many species, drugs that target it could potentially have broad-spectrum use, much like the cephalosporin drugs used to treat many Gram-negative microbes. (New agents for the treatment of infections with Gram-negative bacteria: restoring the miracle or false dawn?)

Merging medicines

AstraZeneca already developed a drug candidate that inhibits LpxH called AZ1; however, the compound was only effective in bacteria if the researchers turned off their efflux pumps — portals on the surface that jettison antibiotics (Novel Antibacterial Targets and Compounds Revealed by a High-Throughput Cell Wall Reporter Assay). “It’s not uncommon that you aren’t able to overcome the efflux problem,” Huseby said.

The team decided to search for compounds with inhibitory potential. After screening multiple hits, they landed on a molecule called JEDI-852. This candidate caught their attention because some bacteria in their screen evolved resistance to it by mutating their LpxH gene, suggesting this compound targets the enzyme.

Unexpectedly, JEDI-852 and AZ1 showed striking similarities. By observing the molecules side by side, Huseby’s team noticed that they share a common core. They decided to synthesize a merged version, with unique functional groups from AZ1 at one end and ones from JEDI-852 at the other. Their newly fashioned molecule, which they called JEDI-1444, proved superior at inhibiting LpxH than AZ1. It even worked in bacteria with functioning efflux pumps, suggesting it is potent enough to kill bacteria even if they expel some of the drug from the cell.

Read more on Diamond website

Image: X-ray crystallography experiments at Diamond’s I04-1 beamline revealed that the new drug, JEDI-1444, binds to the LPS-synthesizing enzyme in the same place as substrates, suggesting it may interfere with the active site. Image credit: Douglas Huseby; adapted from the PNAS publication in accordance with CC-BY 4.0 license.

Diamond celebrates 14,000th paper – A breakthrough in lithium-ion battery research

Diamond celebrates 14,000th paper – A breakthrough in lithium-ion battery research

A new understanding of the role oxygen plays could revolutionise battery development

Diamond Light Source stands as one of the leading research facilities globally, driving scientific advancements. The 14,000th paper published as a result of innovative experiments undertaken at the UK’s national synchrotron highlights the profound impact science can have in addressing the world’s most urgent challenges. A team of researchers from WMG at the University of Warwick, in collaboration with academic partners in the Faraday Institution’s Degradation and FutureCat projects, has conducted a ground-breaking study that bridges the gap between academic models and real-world battery performance.

Their work, recently published in Joule, used a trio of synchrotron techniques – Resonant Inelastic soft X-ray Scattering (RIXS), hard and soft X-ray absorption spectroscopy (XAS) – to investigate the charge compensation mechanism of lithium-ion (Li-ion) battery cathodes during high-voltage operation. This study demonstrates that oxygen plays a significant role through a metal-ligand redox process, emphasising the importance of focusing on surface passivation strategies to mitigate oxygen reactivity with electrolytes, reducing degradation and enhancing safety. By using pilot-line fabricated pouch cells, this work aligns fundamental research with commercial applications and offers crucial insights to improve energy density and cycling stability.

Challenges and Opportunities for High-Energy-Density Batteries

The global transition to a low-carbon future requires the development of low-cost, reliable and long-range electric vehicles, with Li-ion batteries playing a crucial role. However, traditional models of the electronic charge compensation mechanism in layered metal oxide cathodes are insufficient for developing next-generation batteries with increased energy density through high-voltage operation.

Prof Louis Piper explained:

When we talk about trying to increase the energy density of a battery, what that means is being able to remove as many electrons as possible, In a lithium-ion battery, Li-ions move between the anode and a cathode, releasing an equal number of electrons as current. In a commercial layered metal oxide battery, we can pull out about two-thirds of the accessible lithium ions, and therefore, two-thirds of the available electrons. That means the battery is always below its theoretical capacity, but it’s engineered that way to prevent the degradation that occurs when you pull more out. Replacing cobalt with nickel increases the practical capacity of the battery, but it pushes it closer to the point where you see accelerated degradation. Traditional models attribute charge compensation solely to transition metal oxidation, but if that’s true then why does replacing cobalt with nickel change things, and why do we have more problems with safety and oxygen loss as we increase the energy density? We need a better understanding of the metal-ligand redox process to develop safe, stable, higher performance Li-ion cells.

Innovating Battery Research with Real-World Testing

WMG is home to a Battery Scale-Up pilot facility, a suite of cell production equipment covering the full production process cell assembly and testing. It allows researchers to manufacture battery cells in a variety of different formats.

Read more on Diamond website

Image: Graphical abstract of the publication