Using state-of-the-art nanocarriers to beat bacterial resistance

Novel stabiliser-free cubosomes can transport antimicrobial peptides and promote wound healing

In 2018, in England alone, there were an estimated 61,000 antibiotic resistant infections – a 9% rise on the previous year. Infections that don’t respond to antibiotics have the potential to cause bloodstream infections and may require patients to be admitted to hospital. The numbers of antibiotic-resistant bloodstream infections rose by a third between 2014 and 2018. The rise in antibiotic-resistant bacteria is a growing concern worldwide, prompting a search for new antibiotics and alternative strategies for fighting bacteria. One promising approach is the design of lipid-based antimicrobial nanocarriers. However, most of the polymer-stabilised nanocarriers are cytotoxic. In work recently published in  Advanced Functional Materials,  a team of Swiss researchers designed a novel, stabiliser-free nanocarrier for the antimicrobial peptide LL-37 that also promotes wound healing. They demonstrated that stabiliser-free cubosomes show promise as advanced cytocompatible nanovehicles for nutrient and drug delivery. 

Vertebrates have two main immune strategies. In simple terms, the adaptive (or acquired) immune system responds to specific pathogens by producing antibodies. The innate immune system is older (in evolutionary terms) and is found in all kinds of life, from plants and fungi to insects and multicellular organisms. The innate immune system makes use of less specific defence mechanisms, including physical barriers (such as skin or bark), clotting factors in blood or sap, and specialised cells that attack foreign substances. 

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Image : Graphical representation of a cubosome. The coloured surface resembles the lipid-water interface with the confined water channels. The channel diameter is typically in the range of 10 nanometres, with the overall size of the cubosomes being several hundred nanometres.

The benefits of Open Data with ExPaNDS

Diamond is a key collaborator in this European project, which will be mapping the data behind the thousands of published scientific papers

ExPaNDS, alongside the Photon and Neutron Open Science Cloud (PaNOSC) are European H2020 projects who are working towards the development of the European Open Science Cloud (EOSC).

The Photon and Neutron Research Infrastructures (PaN RIs) containing free electron laser, synchrotron light and neutron sources are generating petabytes of research data each year and such vast amounts of data can be hard to share. Researchers around the globe use the data to advance knowledge across a variety of societal challenges. These challenges can be found in energy, transport, healthcare, food safety, and sustainable living to list only a few.

Discovery of a novel magnetic skyrmion surface state

Skyrmions get perpendicular – and push the door open for high density data storage

Scientists from ShanghaiTech University, Diamond Light Source, the SOLEIL synchrotron and University of Oxford report in a recent issue of Nano Letters on their discovery of a novel skyrmion surface state that exists in applied in-plane fields – much different from the usual out-of-plane geometry. In this geometry, magnetic signals from the skyrmion lattice phase settle down in inconvenient reciprocal space locations, making resonant elastic X-ray scattering (REXS) on the chiral magnet Cu2OSeO3 a challenging job to carry out. By combining the complementary capabilities of the soft X-ray diffractometers at two synchrotrons (Diamond and SOLEIL) on the very same sample, the new state was unambiguously identified.

>Read more on the Diamond Light Source website

Image: Illustration of the conventional in-plane skyrmion state (a) and the novel perpendicular skyrmion state (b) in the non-centrosymmetric skyrmion system Cu2OSeO3. Whereas a conventional planar skyrmion takes up an area of A=d2 (d is the skyrmion diameter), a perpendicular skyrmion has a much reduced lateral footprint of A = w d (with w the width of the ridge) which is advantages for skyrmion memory applications. The REXS experiments were carried out in the RASOR diffractometer at beamline I10 in Diamond, and in RESOXS at the beamline SEXTANTS in Soleil (St. Aubin, France).

Understanding more about the ExPaNDS project

Diamond is a key collaborator in this European project, which will be mapping the data behind the thousands of published scientific papers

ExPaNDS is the European Open Science Cloud (EOSC) Photon and Neutron Data Service, which is a collaboration project between ten national Photon and Neutron Research Infrastructures (PAN RIs). This ambitious project will create opportunities for facilities’ users to access the data behind the thousands of successful published scientific papers generated by Europe’s PaN RIs – which every year create petabytes of data.
ExPaNDS will link all relevant data catalogues to ensure that any scientific research communities have access to both the raw data collected that is linked to their session(s) at these facilities, and the relevant peer review articles produced as a direct result of their usage.

The project brings together a network of ten national PaN RIs from across Europe as well as EGI, a federated e-Infrastructure set up to provide advanced computing services for research. In order to do this, ExPaNDS will develop a common ontology for all the elements of these catalogues, a roadmap for the back-end architecture, functionalities and a powerful taxonomy strategy in line with the requirement of the EOSC user community.

>Read more on the Diamond Light Source website
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ExPaNDS presentation video

Learning how breast cancer cells evade the immune system

Cancer cells have ways to evade the human immune system, but research at UK’s Synchrotron, Diamond could leave them with nowhere to hide.

Announced on World Cancer Day, the latest research (published in Frontiers in Immunology) by Dr Vadim Sumbayev, together with an international team of researchers, working in collaboration with Dr Rohanah Hussain and Prof Giuliano Siligardi at Diamond Light Source.  They have been investigating the complex defence mechanisms of the human immune system and how cancer cells in breast tumours avoid it. In particular, they sought to understand one of the biochemical pathways leading to production of a protein called galectin-9, which cancer cells use to avoid immune surveillance. Dr Vadim Sumbayev explains, The human immune system has cells that can attack invading pathogens, protecting us from bacteria and viruses. These cells are also capable of killing cancer cells, but they don’t. Cancer cells have evolved defence mechanisms that protect them from our immune system, allowing them to survive and replicate, growing into tumours that may then spread across the body. Unfortunately, the molecular mechanisms that allow cancer cells to escape host immune surveillance remain poorly understood.  So, with a growing body of evidence suggesting that some solid tumours also use proteins called Tim-3 and galectin-9 and to evade host immune attack, we chose to study the activity of this pathway in breast and other solid and liquid tumours. 

>Read more on the Diamond Light Source website

Image: Breast cancer cell-based pathobiochemical pathways showing LPHN-induced activation of PKCα, which triggers the translocation of Tim-3 and galectin-9 onto the cell surface which is required for immune escape.

Sizing up red phosphorus for use in future battery technologies

A step forward in the search for better anodes for sodium-ion batteries

In 2015, the world used around 16 TW of energy, and this is predicted to rise to about 24 TW by 2035. The need for high-performing energy storage is growing, with the increased use of both intermittent, renewable power sources and electric vehicles. The current technology of choice is lithium-ion batteries (LIBs), which have high specific energies, rate capabilities, and cycle lives. However, LIBs rely on lithium and cobalt, two elements with an uneven geographical distribution. Disruptions to supply can cause price spikes, and there are concerns that the world’s total cobalt reserves may not meet future demand. Scientists are therefore investigating the potential of other battery technologies, which use cheap and widely available materials, such as sodium-ion batteries (SIBs). Although operation and manufacturing processes for SIBs are similar to those for LIBs, they cannot use the graphite anodes that are common in LIS. In research recently published in Energy Fuels, a team of researchers from the University of Oxford investigated how the particle-size distribution of red phosphorus affects the performance of composite anodes for SIBs.

Image: a) TEM image of the composite material made by mixing phosphorus (Dv90 = 0.79 μm) with graphite for 48 h in which graphene planes can be seen on the surface of the phosphorus particle. (b) Plotting the ratio between the integrated areas of the peaks fitted on the photoelectron spectra collected from the composite versus the probing depth shows that surficial P–C chemical bonds gradually decrease and P–P bonds increase as we move deeper toward the particle bulk. The areas are calculated from the fit shown in panels c–e, with the photoelectron spectra of the P 2p region acquired using increasing incident radiation energy.

>Read more on the Diamond Light Source website

New optical device opens path for extreme focusing of X-rays

Adaptable refractive correctors for X-ray optics

An innovative new type of optical component for X-rays has been developed by a scientific team in the Optics and Metrology Group at Diamond Light Source. This new optical component is designed to correct for the effect of imperfections in the optical elements used for focusing of X-rays. It works by introducing a controlled change to the X-ray’s phase. It is known as an “adaptable refractive corrector” – so called because the corrector uses refraction and can  adapt  the correction to the unique imperfection of any optical element. The researchers have designed and tested such a component at Diamond obtaining reductions in the effect of the imperfections in a range of mirror and lens focusing optical elements by a factor of up to 7. This development is expected to have application to new developing techniques such as hard X-ray microscopy at the nanometre scale.

>Read more on the Diamond Light Source website

Image: Schematic showing the adaptable corrector with a double mirror system.

First structure of a DNA crosslink repair ligase determined

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

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

Dr Peijun Zhang, Director of eBIC notes that:

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

>Read more on the Diamond Light Source website

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

Suspending sample droplets with sound waves

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

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

>Read more on the Diamond Light Source website

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

Worldwide scientific collaboration develops catalysis breakthrough

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

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

>Read more on the Diamond Light Source website

Image: Andy Beale works at Diamond Light Source.

Pirbright Institute grants a new licence for FMDV vaccine development

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

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

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

>Read more on the Diamond Light Source website

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

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

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

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

>Read more on the Diamond Light Source website

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

Feeling the strain: shear effects in magnetoelectric switching

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

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

>Read more on the Diamond Light Source website

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

Potassium hunting on protein factories

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

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

>Read more on the Diamond Light Source website

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

How stained glass can help in the battle against superbugs

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

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

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