New targets for antibodies in the fight against SARS-CoV-2

An international team of researchers examined the antibodies from a large cohort of COVID-19 patients. Due to the way antibodies are made, each person that is infected has the potential to produce many antibodies that target the virus in a slightly different way. Furthermore, different people produce a different set of antibodies, so that if we were to analyse the antibodies from many different patients, we would potentially be able to find many different ways to neutralise the virus.

The research article in the journal Cell is one of the most comprehensive studies of its kind so far. It is available online now and will be published in print on 15 April. These new results now show that there are many different opportunities to attack the virus using different antibodies over a much larger area than initially thought/mapped.

Professor Sir Dave Stuart, Life Sciences Director at Diamond and Joint head of Structural Biology at the University of Oxford, said:

SARS CoV-2 is the virus that causes COVID-19. Once infected with this virus, the human immune system begins to fight the virus by producing antibodies. The main target for these antibodies is the spike protein that protrudes from the virus’ spherical surface. The spike is the portion of the virus that interacts with receptors on human cells. This means that if it becomes obstructed by antibodies, then it is less likely that the virus can interact with human cells and cause infection.

By using Diamond Light Source, applying X-ray crystallography and cryo-EM, we were able to visualise and understand antibodies interact with and neutralize the virus. The study narrowed down the 377 antibodies that recognize the spike to focus mainly on 80 of them that bound to the receptor binding domain of the virus, which is where the virus spike docks with human cells.

Read more on the Diamond website

Image: Figure from the publication showing how the receptor binding domain resembles a human torso.

Credit: The authors (Cell DOI: 10.1016/j.cell.2021.02.032)

First glimpse of intricate details of Little Foot’s life

In June 2019, an international team brought the complete skull of the 3.67-million-year-old ‘Little Foot’ Australopithecus skeleton, from South Africa to the UK and achieved unprecedented imaging resolution of its bony structures and dentition in an X-ray synchrotron-based investigation at Diamond. The X-ray work is highlighted in a new paper in e-Life, published today focusing on the inner craniodental features of ‘Little Foot’. The remarkable completeness and great age of the ‘Little Foot’ skeleton makes it a crucially important specimen in human origins research and a prime candidate for exploring human evolution through high-resolution virtual analysis.

To recover the smallest possible details from a fairly large and very fragile fossil, the team decided to image the skull using synchrotron X-ray micro computed tomography at the I12 beamline at Diamond, revealing new information about human evolution and origins. This paper outlines preliminary results of the X-ray synchrotron-based investigation of the dentition and bones of the skull (i.e., cranial vault and mandible).

Read more on the Diamond website

Image: Fossil skull in Diamond’s beamline I12

Credit: Diamond Light Source

New Data sheds light on genesis of our body’s powerhouses

The mitochondria and its protein making “plants” – mitoribosomes

Scientists uncover for the first time how the body’s energy makers are made using Cryo-Electron Microscopy (cryo-EM) at eBIC within Diamond.

A new paper, published in Science on the 19th February, by an international team of researchers reports an insight into ‘the molecular mechanism of membrane-tethered protein synthesis in mitochondria’. This is a fundamental understanding of how the human mitoribosome functions and could explain how it is affected by mutations and deregulation that lead to disorders such as deafness and diseases including cancer development. 

Mitochondria are intracellular organelles which serve as tiny but potent powerhouses in our body. They use oxygen which we inhale and derivatives from food we eat to produce more than 90% of our energy, and therefore effectively support our life. Mitochondria are particularly important in high-energy demanding organs such as heart, liver, muscles and brain. For example, almost 40% of each heart muscle cell is made up of mitochondria.

Read more on the Diamond website

Image: The mitoribosome is attached to its membrane adaptor as it synthesises a bioenergetic protein (glow yellow).

Credit: Dan W. Nowakowski and Alexey Amunts

Diamond celebrates 10,000th paper – A breakthrough in chiral polymer thin films research

This could fundamentally change the technology landscape by enabling a new generation of devices

A recent paper in Nature Communications by an international team of collaborative researchers marks the 10,000th published as a result of innovative research at Diamond Light Source, the UK’s national synchrotron. This study presents disruptive insights into chiral polymer films, which emit and absorb circularly polarised light, and offers the promise of achieving important technological advances, including high-performance displays, 3D imaging and quantum computing.https://player.vimeo.com/video/502596383

Chirality is a fundamental symmetry property of the universe. We see left-handed (LH) and right-handed (RH) mirror image pairs in everything from snails and small molecules to giant spiral galaxies. Light can also have chirality. As light is travelling, its internal electric field can rotate left or right creating LH or RH circular polarisation. The ability to control and manipulate this chiral, circularly-polarised light presents opportunities in next-generation optoelectronics (Figs 1a and 1b). However, the origin of the large chiroptical effects in polymer thin films (Figs 1c and 2) has remained elusive for almost three decades. In this study, a group of researchers from Imperial College London, the University of Nottingham, the University of Barcelona, the Diamond Light Source and the J.A. Woollam Company made use of Diamond’s Synchrotron Radiation Circular Dichroism beamline (B23) and the Advanced Light Source in California.

Read more on the Diamond website

Image: In situ chiroptical response of ACPCA and cholesteric chiral sidechain polymers (CSCP) thin films. In situ CD spectra recorded during heating and cooling of ACPCA (F8BT: aza[6]H) and CSCP (cPFBT) thin films (note blue represents low temperatures and red represents high temperatures), (c) and (d) the CD intensity recorded at 480nm as a function of temperature during heating (red) and cooling (blue), and (e) and (f) CD intensity of thin films held at 140°C as a function of time for [P] (turquoise) and [M] (purple) systems (note the different time on-axis).

New type of molecular knot discovered

Scientists have developed a way of braiding three molecular strands enabling tighter and more complex knots to be made than has previously been possible. 

The paper, published in Nature Chemistry reports the synthesis of a new type of molecular knot, called an endless knot (or 7-4 knot). This type of knot cannot be made from helices – simply twisting strands together and joining the ends – a technique used to make complex molecular knots before.

A team, from the University of Manchester, employed a 3×3 interwoven molecular grid as an intermediate and key structure – they solved this key structure using single-crystal X-ray diffraction techniques on Diamond’s I19 beamline. The bright synchrotron light on I19 was fundamental to the discovery as without it there would not be proof that the knot strands were woven in the correct way.

Read more on the Diamond website

Image: A new type of molecular knot, called an endless knot (or 7-4 knot).

Credit: David Leigh, University of Manchester.

Cooking pollution more resilient than previously thought

Following research undertaken at Diamond, particulate emissions from cooking have been discovered to stay in the atmosphere for longer than initially thought, causing a prolonged contribution to poor air quality and human health.

A new study, led by researchers at the University of Birmingham, demonstrated how cooking emissions can survive in the atmosphere over several days, rather than being broken up and dispersed.

The team collaborated with Diamond, the University of Bath and the Central Laser Facility to show how these fatty acid molecules react with molecules found naturally in the earth’s atmosphere. During the reaction process, a coating is formed around the outside of the particle that protects the fatty acid inside from gases such as ozone which would otherwise break up the particles.

This research was made possible by using Diamond’s powerful X-ray beamline (I22). For the first time researchers we able to recreate the reaction process in a way that enables it to be studied in laboratory conditions.

Read more on the Diamond website

Effective new target for breast cancer treatment

An international study led by scientists at the University of Sussex has provided strong evidence for an effective new target for breast cancer treatment. The five-year study, called “The structure-function relationship of oncogenic LMTK3” published in Science Advances, involved researchers from seven institutions across three countries including Diamond. 

The study suggests that LMTK3 inhibitors could be effectively used for the treatment of breast cancer, and potentially other types of cancer. The structure of oncogenic LMTK3 (Lemur Tyrosine Kinase 3 ) determines its role and functions allowing drug inhibition as a new therapeutic strategy.

It is hoped the research will allow the further development and optimisation of LMTK3 inhibitors as a new type of orally-administered anticancer drug for patients and have potential value not only for breast cancer patients but also for lung, stomach, thyroid and bladder cancer patients.

Read more on the Diamond Light Source website

Image: Crystal structure of LMTK3
Credit: University of Sussex

Hybrid photoactive perovskites imaged with atomic resolution for the first-time

A huge step towards better performing solar cells – a collaboration identified information previously invisible using Diamond’s ePSIC microscopes of Oxford University’s Departments of Materials and Physics

A new technique has been developed allowing reliable atomic-resolution images to be taken, for the first time, of hybrid photoactive perovskite thin films.- highly favourable materials for efficient photovoltaic and optoelectronic applications. These images have significant implications for improving the performance of solar cell materials and have unlocked the next level of ability to understand these technologically important materials. The breakthrough was achieved by a joint team from the University of Oxford and Diamond who have just released a new paper published in Science.

Using the ePSIC (the Electron Physical Science Imaging Centre) E02 microscope and the ARM200 microscope in at the Department of Materials, University of Oxford, the team developed a new technique which allowed them to image the hybrid photoactive perovskites thin films with atomic resolution. This gave them unprecedented insights into their atomic makeup and provided them with information that is invisible to every other technique.

Read more on the Diamond website

Image: An example of one of the images obtained using the new protocol, which illustrates several of the phenomena that the team has been able to describe for the first time, including a range of grain boundaries, extended planar defects, stacking faults, and local inclusions of non-perovskite material.

Diamond helps uncover how an untreatable cancer-causing virus affects immune cells

Scientists have found that human T-cell lymphotropic virus, type 1 (HTLV-1) hijacks cellular machinery to establish an infection.  

Research was undertaken using cutting-edge visualisation techniques such as X-ray crystallography, which was undertaken at Diamond, and single-particle cryo-electron microscopy (cryo-EM).  

HTLV-1 is a virus that affects T cells, a type of white blood cell which plays a crucial role in our immune system. Currently, between five and 20 million people worldwide are infected by HTLV-1 and no cure or treatment is available. While most people infected with the virus do not experience symptoms, around two to five per cent will go on to develop adult T-cell leukaemia (ATL).  

New research, led by a team from Imperial College London and the Francis Crick Institute, shows in atomic detail how HTLV-1 infects immune cells. By providing a more nuanced understanding of how the virus establishes infection in the body, the research will help to support the development of new, targeted therapies. 

Read more on the Diamond Light Source website

Image: Scanning electron micrograph of a human T lymphocyte (also called a T cell) from the immune system of a healthy donor. Credit: NIAID

A new enzyme cocktail can digest plastic waste six times faster

Research undertaken at Diamond has allowed scientists to create a super-enzyme that degrades plastic bottles six times faster than before.

The super-enzyme, derived from bacteria that lives on a diet of plastic, enables the full recycling of plastic bottles. 

Plastic pollution is a global threat as plastics are rarely biodegradable and they can remain in the environment for centuries. One of the most abundant plastics that contributes hugely to this dire situation is poly(ethylene terephthalate) (PET). 
 
PET is used largely in textiles, where it is commonly referred to as polyester, but it is also used as packaging for liquids and foodstuffs. PET’s excellent water-repellent properties led to it being the plastic of choice for soft drink bottles. However, the water resistance of PET means that they are highly resistant to natural biodegradation and can take hundreds of years to break down in the environment. 

In 2018, researchers discovered that a unique bacterium (Ideonella sakaiensis 201-F6) was found feeding on waste from an industrial PET recycling facility. The bacterium had the amazing ability to degrade PET and use it to provide carbon for energy. Central to this ability was the production of a PET-digesting enzyme, known as PETase. 

Read more on the Diamond website

New discovery will have huge impact on the development of future battery cathodes

A new paper published today in Nature Energy reveals how a collaborative team of researchers have been able to fully identify the nature of oxidised oxygen in the important battery material – Li-rich NMC – using RIXS (Resonant Inelastic X-ray Scattering) at Diamond. This compound is being closely considered for implementation in next generation Li-ion batteries because it can deliver a higher energy density than the current state-of-the-art materials, which could translate to longer driving ranges for electric vehicles. They expect that their work will enable scientists to tackle issues like battery longevity and voltage fade with Li-rich materials.

The paper, ‘First cycle voltage hysteresis in Li-rich 3d cathodes associated with molecular O2 trapped in the bulk’ by a joint team from the University of Oxford, the Henry Royce and Faraday Institutions and Diamond, examines the results of their investigations to better understand the important compound known in the battery industry as Li-rich NMC (or Li1.2Ni0.13Co0.13Mn0.54O2).   

Principal Beamline Scientist on I21 RIXS at Diamond, Kejin Zhou,said:

Our work is much about understanding the mysterious first cycle voltage hysteresis in which the O-redox process cannot be fully recovered resulting in the loss of the voltage hence the energy density.

Read more on the Diamond website

Image: A previous study (Nature 577, 502–508 (2020)) into this process made by the same research team, at the I21 beamline at Diamond, reported that, in Na-ion battery cathodes, the voltage hysteresis is related to the formation of molecular O2 trapped inside of the particles due to the migration of transition metal ions during the charging process.

Ocean acidification risks deep-sea coral reef collapse

Diamond X-rays were used in a recent study that suggests climate change is triggering changes to the chemistry of deep-sea coral reefs which may cause their foundations to become brittle. 

Reefs are home to a multitude of aquatic life and the underlying structures of these reefs could fracture as a result of increasing ocean acidity caused by rising levels of carbon dioxide. 

Rising acidity 

Researchers measured the lowest and most acidic pH level ever recorded on living coral reefs hundreds of metres below the surface of the ocean in Southern California. The corals were then raised in the lab for one year under the same conditions. 

Scientists observed that the skeletons of dead corals, which support and hold up living corals, had become porous due to ocean acidification and rapidly become too fragile to bear the weight of the reef above them. The Diamond Manchester Imaging Branchline (I13-2) enabled the team to retrieve phase sensitive images that revealed gradients and de-mineralisation profiles in the coral samples. 

Read more on the Diamond website

Image: Lophelia pertusa skeleton with evidence of dissolution around the outside walls. Image: Sebastian Hennige

Bone breakages and hip fracture risk is linked to nanoscale bone inflexibility

Experiments carried out at Diamond using high energy intense beams of X-rays examined bone flexibility at the nanoscale. This allowed scientists to assess how collagen and minerals within bone flex and then break apart under load – in the nanostructure of hip bone samples.  

The report’s findings suggest that doctors should look not only at bone density, but also bone flexibility, when deciding how to prevent bone breakages. 

New research undertaken at Diamond’s Small Angle X-ray Scattering beamline (I22) has highlighted a gap in preventative treatment in patients prone to bone fractures.  The study, published in Scientific Reports and led by Imperial College London, found that flexibility as well as density in the bone nanostructure is an important factor in assessing how likely someone is to suffer fractures. 

Read more on the Diamond website

Image: Nanostructure: Collagen and mineral strain under load. Image: Shaocheng Ma, Imperial College London.

Diamond is set to help develop the first fully electric Bentley and contribute to sustainable luxury mobility

A three-year research project aims to deliver a break-through in e-axle electric powertrains. Led by Bentley Motors, the project will be delivered in partnership with Innovate UK and nine-partners, including Diamond.  

Diamond scientists will be working with Bentley Motors on a three-year research study that promises to transform electric vehicle powertrains.

The project will utilise a fully integrated, free from rare-earth magnet e-axle that supports electric vehicle architectures. This reinforces Bentley’s ambition to lead sustainable luxury mobility and introduce the first fully electric Bentley by 2026.

Diamond will be contributing to this ground-breaking project by performing imaging using the unique Joint Engineering, Environment and Processing (JEEP) beamline (I12). I12 will image the motor at full speed to measure the temperature changes using diffraction in the rotor and stator parts of the motor, as the performance is pushed the temperature in the motor increases.

Read more on the Diamond website

Image:  OCTOPUS e-axle  Image: Bentley Motors

World first for Synchrotron InfraRed Photo-Thermal in Life NanoSciences

Measuring drug-induced molecular changes within a cell at sub-wavelength scale

Synchrotron InfraRed Nanospectroscopy has been used for the first time to measure biomolecular changes induced by a drug (amiodarone) within human cells (macrophages) and localized at 100 nanometre scale, i.e. two orders of magnitude smaller than the IR wavelength used as probe. This was achieved at the Multimode InfraRed Imaging and Micro Spectroscopy (MIRIAM) beamline (B22) at Diamond Light Source, the UK’s national synchrotron facility.

This is a major scientific result in Life Sciences shared by an international team made up of researchers from the School of Cancer and Pharmaceutical Science at Kings College London, the Department of Pharmaceutical Technology and Bio-pharmacy at University of Vienna, and the scientists of the MIRIAM B22 beamline at Diamond.

Read more on the Diamond website

Image: Schematic of Synchrotron photo-thermal IR nano-spectroscopy on mammalian cell at beamline B22.

A polymer coating makes Metal Organic Frameworks better at delivering drugs

Researchers use Synchrotron InfraRed microspectroscopy to study the dynamics of drug release from MOFs

How to efficiently deliver targeted, controlled and time-released doses of drugs is a significant challenge for biomedicine. Finding solutions to this challenge would result in substantial benefits for patients, including more effective drug therapy and fewer undesirable side effects. The porous nature of metal-organic frameworks (MOFs) makes them attractive candidates for drug-delivery systems as they can be tailored to hold and transport a variety of encapsulated guest molecules. To this end, employing MOFs as a drug delivery vehicle could offer potential solutions to accomplish the targeted and controlled release of anti-cancer drugs. However, understanding the precise chemical and physical transformations that MOFs undergo as these guest molecules are released is challenging. In work recently published in ACS Applied Materials & Interfacesresearchers from the University of Oxford, University of Turin, and Diamond Light Source used a combination of experimental and theoretical techniques to address this problem. They show how the combination of hydrophilic MOF-encapsulated drug with a hydrophobic polymeric matrix is a highly promising strategy to tune the drug release rate for optimal delivery. Their results demonstrate that high-resolution synchrotron InfraRed microspectroscopy is a powerful in situ technique for tracking the local chemical and physical transformations, revealing the dynamics underpinning the controlled release of drug molecules bound to the MOF pores.  

Read more on Diamond Light Source website

Image: Using synchrotron infrared radiation to track the drug release process from MOF/Polymer composites.