Lightsource research on SARS-CoV-2

Coronaviruses are a family which includes the common cold, SARS, MERS and the current outbreak of the disease COVID-19, caused by the SARS-CoV-2 virus.
Several facilities of our collaboration have started research about SARS-CoV-2 virus or launched open calls for rapid access. This post will be updated regularly.

Publications on SARS-CoV-2 Rapid Access




Publications

The Canadian Light Source (Canada) has created a specific page highlighting their COVID-19 research: COVID-19 research at the Canadian Light Source

BESSY II at HZB (Germany) has set up a page where it shows their contributions to the research on SARS-CoV-2 , see here

DESY (Germany) has launched a new page dedicated to Corona Research: https://www.desy.de/news/corona_research/index_eng.html

Diamond Light Source (UK) has created a specific website “Coronavirus Science” with platforms for various audiences: scientific community, general public and the media: https://www.diamond.ac.uk/covid-19.html

ELETTRA (Italy) has launched a new page dedicated to COVID-19 research: https://www.elettra.eu/science/covid-19-research-at-elettra.html

The Photon Division of PSI (Switzerland) have collated many information linked to their institute on coronavirus-relevant research (recent publications, rapid access…): https://www.psi.ch/en/psd/covid-19

ALBA (Spain) has set up a dedicated area on their website for information related to COVID-19 (rapid access, publications etc): https://www.albasynchrotron.es/en/covid-19-information/

The ALS (CA/USA) has created a page listing all COVID-19 related research: https://als.lbl.gov/tag/covid-19/

Published articles

2021.04.16 Diamond Light Source (UK) article on their website: https://lightsources.org/2021/04/16/massive-fragment-screen-points-way-to-new-sars-cov-2-inhibitors/

2021.04.14 SLAC (CA / USA), article also with news about research at Stanford Synchrotron Radiation Lightsource (SSRL): https://www6.slac.stanford.edu/news/2021-04-14-researchers-search-clues-covid-19-treatment-help-synchrotron-x-rays.aspx

2021.04.07 Diamond Light Source (UK), article on their website: First images of cells exposed to COVID-19 vaccine – – Diamond Light Source

2021.04.05 ALS (CA/USA) blog post on Berkeley Lab Biosciences website https://biosciences.lbl.gov/2021/04/05/new-covid-19-antibody-supersite-discovered/

2021.04.02 PETRA III at DESY (Germany), article and animation on their website DESY X-ray lightsource identifies promising candidate for COVID drugs

2021.03.26 Diamond Light Source (UK), article and video on their website: New targets for antibodies in the fight against SARS-CoV-2

2021.02.23 Australian Light Source (ANSTO) Australia, article on their website: Progress on understanding what makes COVID-19 more infectious than SARS

2020.12.02 ESRF (France), article and video on their website: ESRF and UCL scientists awarded Chan Zuckerberg Initiative grant for human organ imaging project

2020.11.10 Diamond Light Source (UK), article and video on their website: From nought to sixty in six months… the unmasking of the virus behind COVID-19

2020.10.29 Canadian Light Source (Canada) video on their website: Studying how to damage the COVID-19 virus

2020.10.07 National Synchrotron Light Source II (NSLS-II) at Brookhaven Lab (NY / USA) article on their website: Steady Progress in the Battle Against COVID-19

2020.10.07 Diamond Light Source (UK), article on their website: Structural Biology identifies new information to accelerate structure-based drug design against COVID-19

2020.10.06 MAX IV (Sweden), article on their website: Tackling SARS CoV-2 viral genome replication machinery using X-rays

2020.08.31 SLAC (CA / USA), article also with news about research at Stanford Synchrotron Radiation Lightsource (SSRL): SARS-CoV-2 Spike Protein Targeted for Vaccine

2020.08.27 Diamond Light Source (UK), article on their website: Structural Biology reveals new target to neutralise COVID-19

2020.08.27 Canadian Light Source (Canada) video on their website: Developing more effective drugs

2020.08.25 Australian Synchrotron (ANSTO) (Australia) article on their website: More progress on understanding COVID-19

2020.08.24 DESY (Germany) article on their website: PETRA III provides new insights into COVID-19 lung tissue

2020.08.11 Australian Synchrotron (ANSTO) (Australia) article on their website: Unique immune system of the alpaca being used in COVID-19 research

2020.07.30 Swiss Light Source at PSI (Switzerland) article on their website: COVID-19 research: Anti-viral strategy with double effect

2020.07.29 National Synchrotron Light Source II (NSLS-II) at Brookhaven Lab (NY / USA) article on their website: Ready to join the fight against COVID-19.

2020.07.20 ALBA (Spain) article on their website: A research team from Centro de Investigaciones Biológicas Margarita Salas (CIB-CSIC) uses synchrotron light to study the possible effect of an antitumoral drug of clinical use over the viral cycle of SARS-CoV-2 coronavirus. 

2020.07.15 ALS (USA) article on their website: Antibody from SARS Survivor Neutralizes SARS-CoV-2

2020.07.14 Diamond Light Source (UK), article on their website: Engineered llama antibodies neutralise Covid-19 virus

2020.06.17 European XFEL (Germany) article on their website: Pulling Together: A collaborative research approach to study COVID-19

2020.06.15 European XFEL (Germany) article on their website: Open Science COVID19 analysis platform online

2020.06.09 APS at Argonne National Laboratory (USA) article on their website: Novel Coronavirus Research at the Advanced Photon Source

2020.05. Società Italiana di Fisica publishes an article about research done at Elettra Sincrotrone Trieste (Italy) and the Advanced Light Source (CA / USA): Accelerator facilities support COVID-19-related research

2020.05.27 Diamond Light Source (UK), new animation video demonstrating the work that has been done at Diamond’s XChem facilities.

2020.05.19 Advanced Light Source (CA / USA), article about their latest results: X-ray Experiments Zero in on COVID-19 Antibodies

2020.05.15 Swiss Light Source (Switzerland), article about their first MX results: First MX results of the priority COVID-19 call

2020.05.14 MAX VI (Sweden), article about their research: Tackling SARS CoV-2 viral genome replication machinery using X-rays

2020.05.14 CHESS (NY/USA), article: CHESS to restart in June for COVID-19 research

2020.05.14 the LEAPS initiative brings together many of our European members. The initative published this brochure: Research at LEAPS facilities fighting COVID-19

2020.05.12 Diamond Light Source (UK), article about their collaboration in a consortium: UK consortium launches COVID-19 Protein Portal to provide essential reagents for SARS-CoV-2 research

2020.05.11 Advanced Photon Source (IL/USA), article: Studying Elements from the SARS-CoV-2 Virus at the Bio-CAT Beamline

2020.05.07 European XFEL (Germany), article: European XFEL open for COVID-19 related research

2020.05.06 ESRF (France), article: World X-ray science facilities are contributing to overcoming COVID-19

2020.04.29. BESSY II at HZB (Germany), article: Corona research: Consortium of Berlin research and industry seeks active ingredients

2020.04.29. Swiss Light Source and SwissFEL at PSI (Switzerland), interview series on the PSI website: Research on Covid-19

2020.04.23. PETRA III at DESY (Germany), article: X-ray screening identifies potential candidates for corona drugs

2020.04.21. MAX IV (Sweden), article: BioMAX switches to remote operations in times of COVID-19

2020.04.16. SLAC (CA / USA), article also with news about research at Stanford Synchrotron Radiation Lightsource (SSRL): SLAC joins the global fight against COVID-19

2020.04.15 Berkeley National Lab (CA/ USA), article with a focus on the research at the Advanced Light Source (ALS):
Staff at Berkeley Lab’s X-Ray Facility Mobilize to Support COVID-19-Related Research

2020.04.07 Diamond Light Source (UK), article: Call for Chemists to contribute to the fight against COVID-19
Crowdfunding: COVID-19 Moonshot

2020.04.07. ANSTO’s Australian Synchrotron (Victoria), article: Aiding the global research effort on COVID-19

2020.04.06. National Synchrotron Light Source II (NSLS-II) at Brookhaven Lab (NY / USA), article: Brookhaven Lab Mobilizes Resources in Fight Against COVID-19

2020.04.02. BESSY II at HZB (Germany), article: Corona research: Two days of measuring operation to find the right key

2020.03.31 Diamond Light Source (UK), article: Jointly with Exscientia and Scripps Research, Diamond aims to accelerate the search for drugs to treat COVID-19

2020.03.27 Argonne National Laboratory with the Advanced Photon Source (APS) and other facilities on-site (IL / USA), article: Argonne’s researchers and facilities playing a key role in the fight against COVID-19

2020.03.27 ANSTO’s Australian Synchrotron (Victoria), article and video: Helping in the fight against COVID-19

2020.03.25 PETRA III at DESY (Germany), article: Research team will X-ray coronavirus proteins

2020.03.23 Diamond Light Source (UK) releases its first animation explaining: SARS-CoV-2 Mpro Single Crystal Crystallography

2020.03.25 CERN Courrier (Switzerland) article about synchrotron research on SARS-CoV-2, written by Tessa Charles (accelerator physicist at the University of Melbourne currently based at CERN, completed her PhD at the Australian Synchrotron): Synchrotrons on the coronavirus frontline

2020.03.19 BESSY II at Helmholtz-Zentrum Berlin (Germany), research publication: Coronavirus SARS-CoV2: BESSY II data accelerate drug development

2020.03.19 BESSY II at Helmholtz-Zentrum Berlin (Germany), technique explanation webpage: Protein crystallography at BESSY II: A mighty tool for the search of anti-viral agents

2020.03.16 Diamond Light Source (UK), article on their “Coronavirus Science” website: Main protease structure and XChem fragment screen

2020.03.12. Elettra Sincrotrone (Italy), article on their website: New project to fight the spread of Coronavirus has been approved

2020.03.05. Advanced Photon Source (IL / USA), article on their website: APS Coronavirus Research in the Media Spotlight

2020.03.05. Advanced Photon Source (IL / USA), research publication: “Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2,” bioRXiv preprint  DOI: 10.1101/2020.03.02.968388, Article on their website (source: Northwestern University): New Coronavirus Protein Reveals Drug Target




Rapid access

Scientists can apply for rapid access at following facilities (only member facilities of Lightsources.org are referenced, the most recent published (or updated) call is mentioned first).

  • The National Synchrotron Light Source II (NSLS-II) in NY / USA is offering a streamlined and expedited rapid access proposal process for groups that require beam time for structural biology projects directly related to COVID-19. The Center for Biomolecular Structure team is supporting remote macromolecular crystallography experiments at Beamlines 17-ID-1 (AMX) and 17-ID-2 (FMX) in this research area. To submit a macromolecular crystallography proposal for COVID-19 related research, use the following form:
    https://surveys.external.bnl.gov/n/RapidAccessProposal.aspx
  • The Advanced Photon Source (APS) at Argonne National Laboratory in IL / USA  user program is operational to support:

·         Research on SARS-CoV-2 or other COVID-19-related research that addresses the current pandemic.

·         Critical, proprietary pharmaceutical research.

·         Mail-in/remote access work for any research involving low-risk samples and most medium-risk samples (as defined on the APS ESAF form).

·         Limited in situ research (set-up with one person, and ability to carry out majority of experiment safely remotely)
https://www.aps.anl.gov/Users-Information/About-Proposals/Apply-for-Time

PETRA III at DESY in Germany offers also Fast Track Access for Corona-related research:
https://photon-science.desy.de/users_area/fast_track_access_for_covid_19/index_eng.html

Australian Synchrotron at ANSTO makes its macromolecular crystallography beamlines available to structural biologists in response to the COVID-19 pandemic: https://www.ansto.gov.au/user-access

North American DOE lightsource facilities have created a platform to enable COVID-19 research. There you can find ressources and points of contact to request priority access:
Structural Biology Resources at DOE Light Sources

Elettra Sincrotrone Trieste in Italy opens to remote acces following beamlines: XRD1, XRD2, SISSI-BIO and MCX thanks to an CERIC-ERIC initiative:
https://www.ceric-eric.eu/2020/03/10/covid-19-fast-track-access/
http://www.elettra.eu/userarea/user-area.html

The Advanced Light Source (ALS) at LBNL in California / USA has capabilities relevant to COVID-19 and researchers can apply through their RAPIDD mechanism:
https://als.lbl.gov/apply-for-beamtime/

ALBA Synchrotron in Spain offers a COVID-19 RAPID ACCESS on all beamlines:
https://www.albasynchrotron.es/en/en/users/call-information

SOLARIS Synchrotron in Poland gives acces to its Cryo Electron Microscope thanks to an CERIC-ERIC initiative: https://www.ceric-eric.eu/2020/03/10/covid-19-fast-track-access/

Swiss Light Source and Swiss FEL at PSI in Switzerland offer priority access to combating COVID-19:
https://www.psi.ch/en/sls/scientific-highlights/priority-access-call-for-work-on-combating-covid-19

Diamond Light Source in the United Kingdom opened also a call for rapid access:
https://www.diamond.ac.uk/Users.html

Image: Electron density at the active site of the SARS-CoV-2 protease, revealing a fragment bound
Credit: Diamond Light Source

Catalytic role of oxygen-containing groups on carbon electrodes

The electrochemical reduction of oxygen plays a significant role in many critical applications such as gas sensors, hydrogen peroxide electrosynthesis, and electrochemical energy storage. Oxygen reduction reaction (ORR) drives the operation of fuel cells and metal-air batteries. The latter potentially can provide the highest specific energy among energy storage devices.

To increase the ORR efficiency, a catalyst immobilized on (or mixed with) conductive support is introduced to the positive electrode composition. Usually, porous sp2-carbon materials, like graphene, serve as such supporting materials. Its electronic configuration (sp2) provides the sufficient electric conductivity to the positive electrode. Nevertheless, ORR proceeds too slowly on the neat surface of ideal sp2-carbon in the absence of a catalyst.

The role of graphene imperfections (vacancies, impurity atoms, and functional groups) on catalyzing ORR (mainly in aqueous media) has been under intense investigation during the last decades. However, little is known about the effect of oxygen functionalization of carbon onORR in aprotic media (lacking the acidic protons). The interest in this process, especially in the presence of metal ions in the electrolyte, is relevant for various aprotic metal-oxygen batteries (lithium, sodium, magnesium, etc.) which are now considered as the most promising electrochemical power sources due to their outstanding theoretical performance. For such devices carbon electrodes are highly attractive due to their light weight and low cost, and the effect of carbon surface chemistry on the processes occurring upon battery operation is of great importance.

The present research shows for the first time that oxygenation of carbon electrode surface does not affect the rate of one-electron oxygen reduction in aprotic media. At the same time, in Li+-containing electrolytes, oxygen groups enhance both the rate of electrochemical Li2O2 formation and carbon electrode degradation due to faster oxidation by lithium superoxide (LiO2) intermediate yielding carbonate species as a product.

The research is led by scientists from Lomonosov Moscow State University and the Semenov Institute of Chemical Physics, in collaboration with FriedrichAlexanderUniversität Erlangen-NürnbergIFW DresdenSaint Petersburg State UniversityDonostia International Physics Center and Massachusetts Institute of Technology. 

Read more on the ALBA website

Image: C 1s core level spectra of a) pristine and b) oxidized graphene electrodes before and after discharge. C) Model spectroelectrochemical Li-O2 cell. D) Evolution of C 1s components’ ratios upon discharge for pristine and oxidized graphene.

Giving rice new weapons to fight rice blast disease

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

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

A pain in the paddy field

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

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

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

Read more on the Diamond website

Image: Rice fields in Asia

A properly tailored tail boosts solar-cell efficiency

With the help of structural insights from the Advanced Light Source (ALS), researchers optimized the fit between organic and inorganic ions in a perovskite solar-cell material.

The work increased the material’s power-conversion efficiency and stability and opens up a new avenue for improving the current-carrier dynamics of a promising class of materials.

A photovoltaic rising star

To address the effects of global climate change, it’s essential that we capitalize on energy from the sun. However, although solar energy is freely available, it needs to be converted into usable electricity in a way that’s efficient, cost-effective, and commercially scalable.

Perovskites are high-performance inorganic semiconductors recognized as some of the most promising photovoltaic materials of the future. Perovskite films—thin, lightweight, and flexible—can be produced using low-cost solution-processing techniques, and their power-conversion efficiencies (PCEs) have rapidly risen to the brink of 30% in just 15 years, surpassing conventional silicon panels.

A structure with room to tinker

The most intriguing perovskite materials today are organic–inorganic hybrids. They have the general formula ABX3, in which the inorganic B and X ions form a framework of octahedral cages, and the organic A ions are located in the spaces between the cages.

Previously, it was thought that perovskite electronic performance mainly depended on the B and X electronic orbitals, and that A merely served a structural function. In this work, researchers showed that A-site organic ions with specially designed characteristics can increase charge-carrier mobility and power conversion efficiency while also improving device stability.

Read more on the ALS website

Image: Left: The basic structure of perovskite, a promising solar-cell material, has three types of sites, A (blue), B (gray), and X (purple). Right: By attaching organic tails to the interstitial “A” sites (and testing different linker lengths), researchers improved the material’s photovoltaic response.

Safely Probing Chernobyl Fuel Simulants with X-rays

Researchers used ultrabright x-rays at Brookhaven Lab’s NSLS-II to study the chemical makeup of simulated nuclear materials from Chernobyl, informing better containment strategies

Beamline scientist Sarah Nicholas is pictured at the X-ray Fluorescence Microprobe (XFM) beamline at NSLS-II, where researchers used ultrabright x-rays to visualize the chemical makeup of simulated nuclear materials from Chernobyl.

On this day 35 years ago, an accident at the fourth reactor of the Chernobyl Nuclear Power Plant created one of the worst nuclear disasters in history. As the reactor core melted, it generated a large amount of highly radioactive materials. Today, scientists continue to research those materials to determine the best methods of containment and cleanup.

In a recent study published in the Journal of Materials Chemistry A, scientists at the University of Sheffield characterized the chemical makeup of a specific nuclear material found at Chernobyl, called lava-like fuel-containing materials (LFCMs). These materials, which are comprised of nuclear fuel and melted reactor components like stainless steel and concrete, behave like natural lava, solidifying to form a complex, highly radioactive glass-ceramic. While research has been conducted on LFCMs before, the level of detail those analyses could provide was significantly limited due to the challenges of handling these radioactive materials.

Read more on the BNL website

Image: Beamline scientist Sarah Nicholas is pictured at the X-ray Fluorescence Microprobe (XFM) beamline at NSLS-II, where researchers used ultrabright x-rays to visualize the chemical makeup of simulated nuclear materials from Chernobyl.

Credit: BNL

Surprising behavior of a fatty acid enzyme with potential biofuel applications

Derived from microscopic algae, the rare, light-driven enzyme converts fatty acids into starting ingredients for solvents and fuels.

Although many organisms capture and respond to sunlight, it’s rare to find enzymes – proteins that promote chemical reactions in living things – that are driven by light. Scientists have identified only three so far. The newest one, discovered in 2017, is called fatty acid photodecarboxylase (FAP). Derived from microscopic algae, FAP uses blue light to convert fatty acids into hydrocarbons that are similar to those found in crude oil.

“A growing number of researchers envision using FAPs for green chemistry applications because they can efficiently produce important components of solvents and fuels, including gasoline and jet fuels.” says Martin Weik, the leader of a research group at the Institut de Biologie Structurale at the Université Grenoble Alpes.

Weik is one of the primary investigators in a new study that has captured the complex sequence of structural changes, or photocycle, that FAP undergoes in response to light, which drives this fatty acid transformation. Researchers had proposed a possible FAP photocycle, but the fundamental mechanism was not understood, partly because the process is so fast that it’s very difficult to measure. Specifically, scientists didn’t know how long it took FAP to split a fatty acid and release a hydrocarbon molecule.

Experiments at the Linac Coherent Light Source (LCLS) at the Department of Energy’s SLAC National Accelerator Laboratory helped answer many of these outstanding questions. The researchers described their results in Science.

Read more on the SLAC website

Image: A study using SLAC’s LCLS X-ray laser captured how light drives a series of complex structural changes in an enzyme called FAP, which catalyzes the transformation of fatty acids into starting ingredients for solvents and fuels. This drawing captures the starting state of the catalytic reaction. The dark green background represents the protein’s molecular structure. The enzyme’s light-sensing part, called the FAD cofactor, is shown at center right with its three rings absorbing a photon coming from bottom left. A fatty acid at upper left awaits transformation. The amino acid shown at middle left plays an important role in the catalytic cycle, and the red dot near the center is a water molecule.

Credit: Damien Sorigué/Université Aix-Marseille

Direct observation of the ad- and desorption of guest atoms into a mesoporous host

Battery electrodes, storage devices for gases, and some catalyst materials have tiny functional pores that can accommodate atoms, ions, and molecules. How these guest atoms are absorbed into or released from the pores is crucial to understanding the porous materials’ functionality. However, usually these processes can only be observed indirectly. A team from the Helmholtz Zentrum Berlin (HZB) has employed two experimental approaches using the ASAXS instrument at the PTB X-ray beamline of the HZB BESSY II synchrotron to directly observe the adsorption process of atoms in a mesoporous model system. The work lays the foundations for new insights into these kinds of energy materials.

Most battery materials, novel catalysts, and storage materials for hydrogen have one thing in common: they have a structure comprised of tiny pores in the nanometer range. These pores provide space which can be occupied by guest atoms, ions, and molecules. As a consequence, the properties of the guest and the host can change dramatically. Understanding the processes inside the pores is crucial to develop innovative energy technologies.

Read more on the HZB website

Image: From the measurement data, the team was able to determine that the xenon atoms first accumulate on the inner walls of the pores (state 1), before they fill them up (state 2). The X-ray beam penetrates the sample from below.

Credit: © M. Künsting/HZB

Tiny Chip-Based Device Performs Ultrafast Manipulation of X-Rays

Researchers from the U.S. Department of Energy’s Advanced Photon Source (APS) and Center for Nanoscale Materials at Argonne National Laboratory have developed and demonstrated new x-ray optics that can be used to harness extremely fast pulses in a package that is significantly smaller and lighter than conventional devices used to manipulate x-rays. The new optics are based on microscopic chip-based devices known as microelectromechanical systems (MEMS).

“Our new ultrafast optics-on-a-chip is poised to enable x-ray research and applications that could have a broad impact on understanding fast-evolving chemical, material and biological processes,” said research team leader Jin Wang from the X-ray Science Division Time Resolved Research (TRR) Group at the APS. “This could aid in the development of more efficient solar cells and batteries, advanced computer storage materials and devices, and more effective drugs for fighting diseases.”

In new results published in The Optical Society OSA) journal Optics Express, the researchers demonstrated their new x-ray optics-on-a-chip device (Fig. 1), which measures about 250 micrometers and weighs just 3 micrograms, using the TRR Group’s 7-ID-C x-ray beamline at the APS. The tiny device performed 100 to 1,000 times faster than conventional x-ray optics, which that tend to be bulky.

Read more on the APS website

Image: Fig. 1. The photograph shows two MEMS elements on a single chip (A), with the active elements of 250 µm × 250 µm, and the micrograph (B) highlighting the size of the diffractive element, as compared to a section of human hair (C).

Scientists glimpse signs of a puzzling state of matter in a superconductor

Known as “pair-density waves,” it may be key to understanding how superconductivity can exist at relatively high temperatures.

Unconventional superconductors contain a number of exotic phases of matter that are thought to play a role, for better or worse, in their ability to conduct electricity with 100% efficiency at much higher temperatures than scientists had thought possible – although still far short of the temperatures that would allow their wide deployment in perfectly efficient power lines, maglev trains and so on.

Now scientists at the Department of Energy’s SLAC National Accelerator Laboratory have glimpsed the signature of one of those phases, known as pair-density waves or PDW, and confirmed that it’s intertwined with another phase known as charge density wave (CDW) stripes – wavelike patterns of higher and lower electron density in the material.

Observing and understanding PDW and its correlations with other phases may be essential for understanding how superconductivity emerges in these materials, allowing electrons to pair up and travel with no resistance, said Jun-Sik Lee, a SLAC staff scientist who led the research at the lab’s Stanford Synchrotron Radiation Lightsource (SSRL).

Read more on the SLAC website

Image: SLAC scientists used an improved X-ray technique to explore exotic states of matter in an unconventional superconductor that conducts electricity with 100% efficiency at relatively high temperatures. They glimpsed the signature of a state known as pair density waves (PDW), and confirmed that it intertwines with another phase known as charge density wave (CDW) stripes – wavelike patterns of higher and lower electron density in the material. CDWs, in turn, are created when spin density waves (SDWs) emerge and intertwine.

Credit: Jun-Sik Lee/SLAC National Accelerator Laboratory

Beaming in on Coronavirus details

User operation resumed at European XFEL end of March, and the first experiments to receive beamtime are those being carried out at the Single Particles, Clusters, and Biomolecules & Serial Femtosecond Crystallography (SPB/SFX) instrument. They will focus on getting deeper insights into the Coronavirus, and, if successful, can lead to a better understanding of the structure of key Coronavirus proteins. New information about the shapes of these proteins, which the virus needs to copy itself, will aid scientists in their quest to find ways to fight COVID.

“Three user collaborations have proposed experiments that will use two distinct approaches to study the Coronavirus. Two collaborations lead by scientists from DESY and Diamond Light Source will look at the structure and binding of ligands to the proteases of the Coronavirus,” says Adrian Mancuso, leading scientist at the SPB/SFX instrument. A ligand is a molecule that binds another specific molecule or atom. Some ligands deliver a signal during the binding process and can be thought of as signaling molecules, which interact with proteins in target cells called receptors. At the European XFEL, scientists can potentially observe the process of these ligands attaching to proteins at atomic resolution, however, first an ordered crystal of the relevant protein is required. “XFELs are uniquely positioned to watch how irreversible processes in proteins—such as binding of potential drug candidates—happen,” explains Mancuso.

Read more on the European XFEL website

Image: A shot from the control hutch showing one of the first COVID-related beamtimes at SPB/SFX

Credit: European XFEL

A novel approach offers hope for an HCV vaccine

An HCV vaccine is needed, but hard to develop. A structural mimic may be the key to enhancing our immune response

Globally, more than 70 million people were struggling with a chronic hepatitis C virus (HCV) infection in 2015. Although effective drugs are available to treat chronic infections, only 13% of cases received curative treatment. The fact that only 20% have been diagnosed is of even greater concern. Although a minority of newly-infected individuals (10–40%) manage to overcome the disease, most develop a chronic infection. Most acute cases of HCV are asymptomatic, leading to undetected virus transmission. Left untreated chronic HCV can lead to serious liver damage and an increased risk of liver cancer. As curative therapies alone cannot eliminate the virus, a vaccine is required. However, because HCV is very diverse and evolves rapidly to evade the immune system, developing an effective vaccine is challenging. In work recently published in npj Vaccines, scientists from the MRC-University of Glasgow Centre for Virus Research, the University of St. Andrews and Imperial College London describe an alternative strategy that uses a structural mimic to encourage the immune system to make antibodies that can recognise multiple strains of the virus i.e. broadly-neutralising antibodies (bNAbs) against HCV. 

A moving target

With its high genetic diversity and an envelope of ever-changing glycoproteins, HCV is challenging for the human immune system to detect and counteract. The minority of cases in which the virus is successfully cleared from the body show a broad, strong T-cell response and neutralising antibodies during the early phase of infection. Individuals who have previously cleared an HCV infection have an 80% chance of successfully fighting off reinfection, indicating that a protective immune response has been induced and that vaccination is a realistic goal. However, with seven distinct genotypes and more than 60 subtypes, the genetic variation makes it challenging to produce a vaccine that would protect against all infections. 

Read more on the Diamond website

Image: I03 beamline at Diamond

Credit: Diamond Light Source

AI Agent Helps Identify Material Properties Faster

High-throughput X-ray diffraction measurements generate huge amounts of data. The agent renders them usable more quickly.

Artificial intelligence (AI) can analyse large amounts of data, such as those generated when analysing the properties of potential new materials, faster than humans. However, such systems often tend to make definitive decisions even in the face of uncertainty; they overestimate themselves. An international research team has stopped AI from doing this: the researchers have refined an algorithm so that it works together with humans and supports decision-making processes. As a result, promising new materials can be identified more quickly.

A team headed by Dr. Phillip M. Maffettone (currently at National Synchrotron Light Source II in Upton, USA) and Professor Andrew Cooper from the Department of Chemistry and Materials Innovation Factory at the University of Liverpool joined forces with the Bochum-based group headed by Lars Banko and Professor Alfred Ludwig from the Chair of Materials Discovery and Interfaces and Yury Lysogorskiy from the Interdisciplinary Centre for Advanced Materials Simulation. The international team published their report in the journal Nature Computational Science from 19 April 2021.

Read more on the BNL website

Image: Daniel Olds (left) and Phillip M. Maffettone working at the beamline.

Credit: BNL

Massive fragment screen points way to new SARS-CoV-2 inhibitors

Experiment with 2533 fragments compounds generates chemical map to future antiviral agents 

New research published in Science Advances provides a template for how to develop directly-acting antivirals with novel modes of action, that would combat COVID-19 by suppressing the SARS-CoV-2 viral infection. The study focused on the macrodomain part of the Nsp3 gene product that SARS-CoV-2 uses to suppress the host cell’s natural antiviral response. This part of the virus’s machinery, also known as Mac1, is essential for its reproduction: previous studies have shown that viruses that lack it cannot replicate in human cells, suggesting that blocking it with a drug would have the same effect.  

The study involved a crystallographic fragment screen of the Nsp3 Mac1 protein by an open science collaboration between researchers from the University of Oxford, the XChem platform at Diamond, and researchers from the QCRG Structural Biology Consortium at the University of California San Francisco.  The international effort discovered 234 fragment compounds that directly bind to sites of interest on the surface of the protein, and map out chemical motifs and protein-compound interactions that researchers and pharmaceutical companies can draw on to design compounds that could be developed into antiviral drugs.  This work is thus foundational for preparing for future pandemics.   

Read more on the Diamond website

Image: Principal Beamline Scientist on I04-1, Frank von Delft

Credit: Diamond Light Source

Researchers search for clues to COVID-19 treatment

Two groups of researchers drew on SLAC tools to better understand how to target a key part of the virus that causes COVID-19

Vaccination, masks and physical distancing help limit the spread of COVID-19 – but, researchers say, the disease is still going to infect people, and doctors are still going to need better medicines to treat patients. This may be especially true for cancer patients and other at-risk people who may lack a sufficiently strong immune system to benefit from the vaccine. 

Now, two teams working in part at the Department of Energy’s SLAC National Accelerator Laboratory have found some clues that could, down the road, lead to new COVID drugs. 

The researchers, from John Tainer’s lab at MD Anderson Cancer Center and James Fraser’s group at the University of California, San Francisco, focused on a molecular structure that is common to all coronaviruses but has proven especially troublesome in the case of the virus that causes COVID-19. The structure contributes both to the virus’s ability to replicate and to immune system overreactions that have proven particularly deadly.

The trouble, Fraser said, is that scientists don’t know what kinds of molecules would bind to the structure, known as the Nsp3 macrodomain, let alone how to combine such molecules to interfere with its deadly work. 

To remedy that problem, Fraser’s group screened several thousand molecules at facilities including SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) to see where and how well the molecules bound to crystallized forms of Nsp3. The team combined those results with computer models to understand how the molecules might affect the structure of the macrodomain and whether they might help inhibit its function. 

Read more on the SLAC website

Virus recognition skills

A virus recognizes the starting point on the DNA to be packaged inside its protein shell

A bacteriophage – a virus that attacks bacteria – assembles into an infectious species using a powerful nanomachine to stuff its DNA into a protein shell. In several types of phage, this genome packaging motor is composed of several copies of large and small terminase subunits (TerL and TerS, respectively) that attach to a portal into the protein procapsid. 

Figure 1. Envelope of NV1 TerS from SAXS data, overlaid with modeled structure with open HTHs. Circle highlights one HTH motif.

The Cingolani group (Thomas Jefferson U) has now determined the structure of TerS from the Pseudomonas phage PaP3. Phage DNA to be packaged contains multiple copies of the genome, but just one copy is needed to fill a procapsid. Terminases attempt to package this one copy by various methods; in PaP3 a termination signal is provided by the interaction of a specific sequence in the DNA (the cos sequence) with TerS.

A crystal structure of PaP3 TerS reveals a nonameric ring of mixed alpha/beta composition, sitting atop a 9-stranded beta-barrel. Projecting out from the ring are spokes tipped with helix-turn-helix (HTH) DNA-binding domains. In the crystal, with no DNA present, the HTH domains are packed tightly against the inner parts of the nonamer (a “closed” form). Crystals of TerS from the related NV1 phage were also studied; their quality was not as good but the same conformation was found.  BioSAXS coupled to size-exclusion chromatography, at CHESS, was then used to examine the PaP3 TerS structure, and that of the related NV1 protein, in solution. Both turned out to be ~25% larger than predicted from the crystal structure. The molecular envelope determined from SAXS data for NV1 clearly showed protuberances on the outside of the nonameric ring that did not match the crystal structure. However, by rotating the HTH domain of each monomer about an obvious hinge region, an “open” model could be built that fit the SAXS envelope well (Figure 1). 

Read more on the CHESS website

Image: Figure 1. Envelope of NV1 TerS from SAXS data, overlaid with modeled structure with open HTHs. Circle highlights one HTH motif.

New insights into the photochemical activity of titanium dioxide

Not so many compounds are as important to industry and medicine today as titanium dioxide (TiO2). The electronic structure of transition metal oxides is an important factor determining the chemical and optical properties of materials. Specifically for metal-oxide structures, the crystal-field interaction determines the shape and occupancy of electronic orbitals. Consequently, the crystal-field splitting and resulting unoccupied state populations can be foreseen as modeling factors of the photochemical activity. The research on titanium dioxide inaugurated the presence of IFJ PAN scientists in research programs carried out at the SOLARIS synchrotron. The measurements, co-financed by the National Science Center, were carried out at the XAS beamline.

In many chemical reactions, TiO2 appears as a catalyst. As a pigment, it occurs in plastics, paints, and cosmetics, while in medical implants, it guarantees their high biocompatibility. A group of scientists from the Institute of Nuclear Physics of the Polish Academy of Sciences (IFJ PAN) in Krakow, led by Dr. Jakub Szlachetka, engaged in research on the oxidation processes of the outer layers of titanium samples and related changes in the electronic structure of this material. Scientists from the IFJ PAN conducted their latest measurements, co-financed by the National Science Center, at the XAS beamline. They analyzed how X-rays are absorbed by the surface layers of titanium samples previously produced at the Institute under carefully controlled conditions.

Read more on the SOLARIS website