Diamond Light Source – Page 2

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

2025/03/272025/03/31

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, Hf_0.5Zr_0.5O₂(HZO) and Hf_0.88La_0.04Ta_0.08O₂(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:

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.

Breakthrough in next-generation polio vaccines

2025/03/202025/03/24

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:

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.

Targeted Destruction of Disease-Related Proteins

2025/03/172025/03/19

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:

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

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 Cereblon^_midi.

Next, they had to put their crystallised Cereblon^midi 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.

Uncovering ancient text from the Oxford Herculaneum scroll

2025/02/052025/02/06

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.

Image: The Bodleian Libraries Herculaneum scroll.

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

2025/01/222025/01/27

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:

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:

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.

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

Tearing down bacterial membranes with new antibiotics

2025/01/202025/01/20

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-20^th 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.

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

2025/01/172025/01/17

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:

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.

Revolutionising plastic recycling: a breakthrough in enzyme-based depolymerisation

2025/01/142025/01/21

The accumulation of plastic waste in the environment is an ecological disaster and will require multiple solutions to tackle the problem. Despite recent initiatives to close the plastics loop, only 9% of plastic was recycled in 2019, with the remaining waste either incinerated or accumulating in landfills or natural environments, posing hazards to both living and non-living systems. Bioplastics, derived from renewable sources, have been investigated as green alternatives to conventional fossil-based plastics. However, costly synthetic routes and low recyclability continue to challenge the growth of bioplastics. Poly(lactic acid) (PLA) is the most popular polymer for commercial bioplastics, but its recycling is limited by challenging mechanical recycling and slow biodegradation. A team of researchers from King’s College London has developed a generalisable biocatalysis engineering strategy to enhance the use of enzymes to depolymerise a broad class of plastics, in a publication recently published in Cell Reports Physical Science. This novel approach is 84 times faster than the 12-week-long industrial composting process currently used for recycling bioplastic materials

The problem with plastic waste

The demand for conventional plastics such as Poly(lactic acid) (PLA) or poly(ethylene terephthalate) (PET) is increasing, with 460 million tons produced in 2019; a 230-fold increase from the 2 million tons produced in 1950. Plastic waste is a significant environmental issue, with millions of tons of plastic ending up in natural environments each year. Traditional recycling methods are often inefficient and unable to produce high-quality reusable materials. Bioplastics, derived from biological sources such as corn starch and sugarcane, are seen as a more sustainable alternative. However, current methods of bioplastic production are costly and compete with food-based agriculture for land use. Furthermore, mechanical recycling methods generate CO2 and are incapable of producing high-quality reusable materials, leading many retailers to revert to using oil and fossil-based materials. As an example, it takes up to 84 days at 60°C in industrial composting to recycle PLA, with very little valorisation possible.

An innovative solution

In this publication, the team of researchers developed a new protocol to recycle PLA. This method involves different component to help depolymerise the material.

First, they used ionic liquids to solubilise the plastic. Ionic liquids are salts in a liquid state that have unique properties, such as low volatility and high thermal stability. Ionic liquids have been shown to have the ability to solubilise polymers used in common plastics such as PET and PLA. Secondly, they used a commercially available enzyme, a lipase from Candida antarctica (CaLB) to degrade the plastic.

As the enzyme may not be stable in ionic liquid, the researchers performed some chemical modifications in three different steps to preserve enzyme activity.

Researchers performed circular dichroism at Diamond Light Source on the B23 beamline to ensure that the secondary structure of the enzyme was intact after the chemical modifications. Measurements realised on B23 also showed that the thermostability of the modified protein was higher in ionic liquid (> 80°C) compared to the unmodified protein in aqueous solution. This parameter is important, as heat is required to help depolymerise plastics.

Image: Graphical abstract of the publication

Jigsaw puzzle: Deciphering the chloroplast transcription machinery

2025/01/072025/01/10

Chloroplasts are specialised organelles found in plant cells and some algae. Photosynthesis, the process by which light energy is converted into chemical energy, resulting in the production of oxygen and energy-rich organic compounds, takes place in chloroplasts. The number of chloroplasts per plant cell can vary widely, ranging from one in unicellular algae to up to 100 in plants like Arabidopsis and wheat. Chloroplasts have a unique transcription machinery that is more complex than their cyanobacterial ancestors. The plastid-encoded RNA polymerase (PEP) is a multi-subunit complex crucial for transcribing chloroplast genes, which are essential for photosynthesis and plant growth. Despite its importance, the roles of many PEP-associated proteins (PAPs) are poorly understood. Researchers from the John Innes Centre and Diamond Light Source aimed to study the structure of PEP to better understand its composition, assembly, and function. They used cryo-Electron Microscopy (cryo-EM) at the electron Bio Imaging Centre (eBIC) to achieve this goal, providing a detailed view of the PEP complex and its interactions with DNA and RNA. Their work was recently published in Cell.

Before this groundbreaking study, the understanding of the plant plastid-encoded RNA polymerase (PEP) was limited. Researchers knew that PEP is a multi-subunit complex composed of four plastid-encoded subunits similar to bacterial RNA polymerases (RNAPs) and several nuclear-encoded PEP-associated proteins (PAPs). This is the first striking difference compared to bacteria: the complex is significantly larger, as the PAPs seem to be present only in chloroplasts. Furthermore, the exact composition of the complex and roles of these subunits were poorly defined. Previous studies had identified PEP subunits are essential to chloroplast biogenesis, but the detailed structural and functional insights were lacking.

In this study, researchers purified PEP complex using chromatographic separation. It showed that the PEP is a huge complex of 1.1 MDa, more than twice the size of its bacterial counterpart. 19 unique subunits were identified using liquid chromatography techniques coupled with mass spectroscopy: the four subunits that form the core polymerase, and 15 PAPs. The purified PEP samples were functional in transcribing RNA from DNA in assays. This first step was crucial to ensure that the samples used for cryo-EM represents an active complex.

To visualise the PEP complex at high resolution, the researchers used cryo-EM at eBIC. Cryo-EM is ideal for studying large protein complexes in their native state, allowing the researchers to capture the intricate details of PEP and its associated proteins.

Dr Michael Webster commented:

They discovered that the core polymerase of the PEP shares structural similarities with the cyanobacterial RNAP. Also, PAPs encase the core polymerase, forming extensive interactions that likely promote complex assembly and stability. The precise composition of PEP and the position of the PAP subunits with respect to the polymerase were not known prior to this work. The PAP subunits add new capability to the core polymerase. PAP1 and PAP2 add DNA binding and RNA binding, and several PAPs add enzymatic functions. Interestingly, if any single PAP subunit is missing, the polymerase will not function efficiently. Future work will be needed to understand the relationship between all the different PAPs and the core polymerase and what is the precise role of each PAPs.

Image: the PEP complex in chloroplasts.

Solid Electrolytes: A Breakthrough for Safer, High-Performance Batteries

2025/01/022025/01/07

Synchrotron studies shed light on new places to look for high ionic conductivity

Batteries are a critical technology for the transition to a sustainable energy economy. Rechargeable lithium ion (Li ion) batteries power our electronic devices and electric cars and are needed to store energy generated from renewable sources. The design and discovery of new materials underpins the development of high performing and reliable rechargeable batteries that are long-lasting, cost-effective, fast charging, safe and sustainable. Most Li-ion batteries rely on a liquid electrolyte to conduct ions between the anode and cathode. However, liquid electrolytes can leak and are flammable, which can lead to fires. One solution to this issue is to use a solid electrolyte, and researchers at the University of Liverpool have discovered a solid material with high enough Li ion conductivity to replace the liquid electrolytes in current Li ion battery technology, improving safety and energy capacity. Their work, recently published in Science, used a collaborative computational and experimental workflow, synthesising the material in the laboratory, using synchrotron techniques to determine its structure, and demonstrating it in a battery cell. Their disruptive design approach offers a new route to discover more high-performance materials that rely on the fast motion of ions in solids.

A New Pathway to Superionic Conductivity

If you’re looking for a new material for battery electrolytes, then you want something with high ionic conductivity and good chemical compatibility between the solid electrolyte and lithium metal is required. The existing high-performance solid-state electrolytes come from a small number of structural families with transport paths that minimize changes in cation coordination. With the assumption that this is what gives them their high conductivities, the search for new materials has continued along the same lines – emphasising anion packings that provide a single type of Li coordination environment

However, the team at the University of Liverpool has taken a different approach, opting for a design strategy using multiple anions to construct suitable pathways, supported by AI and physics-based calculations. The material they synthesised, Li₇Si₂S₇I, is a pure lithium-ion conductor created by an ordering of sulphide and iodide with many different cation coordination environments that combine to create superionic conductivity. Created from non-toxic earth-abundant elements, the new material operates in a new way and achieves a high enough Li ion conductivity to replace liquid electrolytes.

At the start of the project, computational exploration of the Li-Si-S-I phase field offered up a number of candidate compositions, which were synthesised in carbon crucibles in the lab. Using X-ray Diffraction to identify the materials formed highlighted a novel phase. After suitable crystals for single-crystal diffraction were grown, the team used high resolution single-crystal XRD on Diamond’s I19 beamline to solve the crystal structure.

Image: The figure represents the lithium ions (in blue) moving through the structure

Credit: Liverpool University

Two-dimensional gold nanostructures

2024/12/182025/01/10

An international team of researchers from Hokkaido University, Lund University, MAX IV Laboratory in Sweden, and Diamond Light Source in the UK has made significant progress in synthesising nanostructured two-dimensional gold films. This development could pave the way for advances in catalysis, electronics, and energy conversion.

The research team utilized a bottom-up approach, growing gold monolayers on iridium substrates with boron atoms embedded at the interface. This method produced nearly freestanding gold layers with hexagonal nanoscale patterns, stabilized by boron. The resulting films exhibited notable thermal stability and distinctive electronic properties, addressing the challenges of stabilizing two-dimensional metallic structures.

The facilities at MAX IV Laboratory were central to the research. The MAX IV STM Laboratory facilitated the synthesis of the gold films and their topographic characterization, while the Surface- and Materials Science end station at the FlexPES beamline enabled detailed analysis using techniques such as X-ray Photoelectron Spectroscopy (XPS), X-ray Absorption Spectroscopy (XAS), and Angular Resolved Photoelectron Spectroscopy (ARPES). These complementary approaches provided valuable insights into the structure, bonding, and electronic properties of the films.

“The combination of synthesis and advanced characterization at MAX IV, particularly the ability to study atomic arrangement and surface chemistry in the same sample, was essential to this work,” said Dr. Alexei Preobrajenski of Lund University.

Cancer Research Horizons and Diamond Light Source establish drug discovery partnership

2024/12/102024/12/10

Cancer Research Horizons, the innovation arm of Cancer Research UK, is partnering with Diamond Light Source, the UK’s national synchrotron, to build a world-leading fragment-based drug discovery programme

Diamond Light Source accelerates electrons to near light speed, producing bright light that is directed into research instruments known as beamlines. Cancer Research Horizons and its drug discovery site at Newcastle University have already been using Diamond’s beamlines and XChem facility for fragment-based screening, a powerful approach to identify chemical entities that can be developed rapidly into potent candidates.

The new partnership will build on this existing relationship to improve the throughput, running and analysis of these experiments. By leveraging their combined expertise and resources, the partnership aims to accelerate the drug discovery process and help bring new cancer treatments to patients faster.

Under the agreement, Cancer Research Horizons will fund two on-site postdoctoral research assistants dedicated to optimising the delivery of its in-house and industry-partnered projects. In return, Diamond will provide early access to any proprietary developments to its platform.

The partnership will establish a governance framework to enable Cancer Research Horizons to provide feedback on the industrialisation of Diamond’s Fragment Screening platform. This initiative aims to enhance its appeal to Cancer Research Horizons’ pharmaceutical and biotech partners, driving broader industry engagement.

UK and Switzerland partner for science using neutrons, muons and X-rays

2024/12/092024/12/18

A strategic partnership between research facilities in the UK and Switzerland has been established by the UK International Science Partnerships Fund (ISPF), which will develop new capabilities for science using neutrons, muons and X-rays.

UK facilities – ISIS Neutron and Muon Source (ISIS) and the Diamond Light Source, located at the Rutherford Appleton Laboratory (RAL) – and the Paul Scherrer Institute (PSI), in Switzerland – home to the Swiss Spallation Neutron Source SINQ, the Swiss Muon Source SµS, the Swiss Light Source SLS and the X-ray Free-Electron Laser SwissFEL, will create new scientific capabilities to address global challenges.

These large-scale research infrastructures have a rich history in pushing forward science in key areas for our society, such as net zero technology development, healthcare solutions and therapies, and resilient communications, relying on their ability to study material properties at the atomic and molecular scales. Recent studies have included investigation of materials for enhanced batteries, quantum computing and technologies, and novel drug delivery mechanisms, as well as fundamental science investigations. The ISPF partnership will enable new projects to be taken forward, developing capabilities for research facilities that benefit society overall.

Researchers and technical teams from ISIS, Diamond and PSI have already worked in close collaboration for many years. The ISPF funding will allow an extension of collaborations into new research areas, enabling the development of novel capabilities in both countries. Around 16 projects will be taken forward as part of the programme, with 16 early-career postdoctoral researchers employed to work between the facilities.

Image: Meeting of members of the ISIS – Diamond – PSI partnership at the Rutherford Appleton Laboratory, 27-28 November 2024.

A new authentication technology – A novel technique to fight counterfeiting

2024/12/042024/12/09

In today’s world, the fight against counterfeiting is more critical than ever. Counterfeiting affects about 3% of global trade, posing significant risks to the economy and public safety. From fake pharmaceuticals to counterfeit currency, the need for secure and reliable authentication methods is paramount. Authentication labels are commonly used – such as holograms on bank notes and passports – but there is always a need for new unfalsifiable technologies.

This is where new groundbreaking research recently published in Applied Sciences comes into play. Led by a team of scientists from Oxford University, the University of Southampton, and Diamond Light Source, the UK’s national synchrotron, the work focuses on developing a new technology for writing and reading covert information on authentication labels. This technology leverages the unique properties of Ge₂Sb₂Te₅ thin films, which can change their structure when exposed to specific types of laser light. By using circularly or linearly polarised laser light, the researchers can encode hidden information in these thin films. This information can then be revealed using a simple reading device, making the technology both advanced and accessible. The paper is called ‘Application of Photo-Induced Chirality in Covert Authentication’ and explains how photo-induced chirality in Ge₂Sb₂Te₅ thin films can be exploited to improve authentication.

The significance of this research lies in its potential applications. Authentication labels are essential in various industries, including pharmaceuticals, electronics, and currency. The ability to encode and read covert information securely can help prevent counterfeiting and ensure the authenticity of products. Moreover, the technology’s reliance on existing manufacturing methods makes it a practical solution for widespread use.

To create these new authentication labels, the authors deposited 55nm thick film on a disk substrate. After that, author, Dr Konstantin Borisenko, Research Computing Administrator at University of Oxford explained,

Toxic behaviour: why do tuberculosis bacteria poison themselves?

2024/11/252024/11/29

Tuberculosis bacteria halt their growth with self-toxins that could inspire novel therapeutics

Stealthy bacteria slow down their division when they invade the body to avoid drawing the immune system’s attention. Mycobacterium tuberculosis, the world’s leading bacterial infectious killer, takes a seemingly counterintuitive approach to that end. M. tuberculosis expresses self-toxins that damage its DNA and shut down growth as well as antitoxins to later help recuperate and resume proliferation. By studying these toxin-antitoxin pairs, Durham University microbiologist Professor Tim Blower aims to find ways to mimic the self-toxins with new therapeutics

By conducting X-ray crystallography at Diamond’s I04 beamline, Blower and his colleagues uncovered the structure of toxin-antitoxin complexes, providing insight into how they regulate DNA damaging activity. The findings reveal that the protein pair potentially form two types of complexes. A grouping of two toxins and four antitoxins dominated at body temperature, whereas an equal pairing of two and two were more common in colder conditions, which may reflect how the proteins come together when bacteria live in the environment. These findings change our perspective on how the toxins and antitoxins operate, bringing researchers closer to designing new drugs against a pandemic microbe that continuously evolves resistance to existing antibiotics.

Each year, Mycobacterium tuberculosis leads approximately 10 million people to endure a bloody cough, exhaustion, and fever, and it causes over one million deaths. Doctors typically prescribe patients a course of four to six antibiotics to clear the infection, but the bacteria evolve mechanisms to resist the effects of the drugs. As many as 2.5 percent of tuberculosis patients carry variants of the bacteria resistant to the four most common first-line antibiotics, and that proportion is expected to climb if researchers don’t develop other therapeutics that could kill resistant strains.

Poison control

Blower and the team from Durham University and Newcastle University study mechanisms the bacteria use to limit their own growth in pursuit of inspiration for new drug candidates. Specifically, they focus on an enzyme that controls DNA organisation in the cell and a pair of toxins and antitoxins that regulate this enzyme’s function.

Bacteria and eukaryotes (for instance, humans), organise DNA in the cell differently. Eukaryotic DNA is tightly packaged in the nucleus by histone proteins that wind it up into compact chromosomes. Bacteria, on the other hand, lack histones and rely on DNA to undergo a process called supercoiling. Like how a wound-up rubber band contracts into a small volume, bacterial DNA winds up into a condensed coil to save space. However, supercoiled DNA needs constant maintenance, which involves occasional unwinding and rewinding of the molecules. To this end, an essential enzyme called DNA gyrase cuts the DNA, allows it to untwist, and glues the cut ends back together again, so they can coil again.

Repairing the DNA breaks is essential to the bacteria’s survival because it avoids the build-up of harmful DNA damage and mutations, but sometimes M. tuberculosis interferes with the process. It achieves this using a toxin-antitoxin system that inhibits DNA gyrase. Scientists are still uncertain about the biological role of the toxin, Blower said, but one hypothesis is that by partially shutting down bacterial growth, it prevents antibiotics that target growth machinery from working. Another is that the toxin helps quiescent bacteria evade immune detection as slow-growing microbes tend to slip under the radar. The antitoxin relieves the bacteria, allowing those that survived the accumulation of DNA breaks to seal them back together and resume growth when conditions in the body become favourable.

Researchers developing new therapeutics are drawn to these systems. Suggesting scientists could develop copycat drugs, Professor Blower said:

Chiral magnets in the slow lane

2024/10/242024/10/28

A groundbreaking study led by Thorsten Hesjedal, Gerrit van der Laan, and Shilei Zhang from Oxford, Diamond, and ShanghaiTech University has uncovered unexpected slow relaxation processes in chiral magnets, a discovery that challenges the conventional understanding of magnetic dynamics. The study highlights the critical role of topological defects in slowing down the relaxation of non-collinear magnetic states considered for emerging skyrmionics applications.

Exploring non-collinear magnetic orders

Non-collinear magnetic orders, such as spin spirals and skyrmions, have become a central topic in modern magnetism research. These complex magnetic configurations, characterised by twisted spin textures, have topological properties that make them ideal candidates for next-generation spintronic devices. In particular, magnetic skyrmions are small, stable, and can be moved about at minimal energy cost, making them ideal for advanced information storage technologies.

Typically, when these magnetic textures are disturbed, their relaxation back to equilibrium is believed to occur over a timescale of nanoseconds, as predicted by micromagnetic theories. However, the research team has discovered that under certain conditions, the relaxation processes can extend to hundreds of milliseconds or even seconds.

Revealing the slow dynamics

In their experiment, the researchers studied the archetypal chiral magnet Cu2OSeO3 using a novel time-resolved resonant elastic X-ray scattering (REXS) technique (Fig a). By applying a pulsed magnetic field and measuring the magnetic order’s response, they were able to capture the entire relaxation process in real-time. Surprisingly, the team found that both the conical and skyrmion lattice phases took up to 0.2 seconds to decay to their equilibrium state – a timescale that is eight orders of magnitude longer than conventional predictions (Fig b).

This extended relaxation is attributed to the formation of topological defects, such as dislocations and monopoles, located within the magnetic structure. These defects act as localised disturbances, slowing down the relaxation process as the system strives to unwind and return to its lowest energy state. This behaviour contrasts sharply with the rapid dynamics typically expected in magnetic systems and opens up new questions about the underlying physics of topological textures.

Image: 3D simulation of the skyrmion lattice. (a) Isosurface visualization (𝑚𝑧=0) of a well-ordered 3D SkX phase. During the relaxation process, topological defects (red dots) emerge that break the local skyrmion strings, as shown in (b) and (c). (d) Shared 2D skyrmion plane, cut from the transparent slices in (a)–(c). The three 𝐐𝑖 wave vectors are shown.