Insights into coronavirus proteins using SAXS

A collaboration led by researchers from the European Molecular Biology Laboratory (EMBL) used small angle X-ray scattering (SAXS) at the European XFEL and obtained interesting data on samples containing coronavirus spike proteins including proteins of the isolated receptor biding domain. The results can, for example, help investigate how antibodies bind to the virus. This gives researchers a new tool that may improve understanding of our bodies’ immune response to coronavirus and help to develop medical strategies to overcome COVID-19

SAXS is a powerful technique as it allows researchers to gain insights into protein shape and function at the micro- and nanoscales. The technique has proven to be extremely useful in investigating macromolecular structures such as proteins, especially because it removes the need to crystallize these samples. This means researchers can study the sample in its native form under physiological conditions under which biological reactions occur.

Read more on the European XFEL website

Image: Seen here, the instrument SPB/SFX, where the SAXS experiment was carried out. Using this instrument researchers can study the three-dimensional structures of biological objects. Examples are biological molecules including crystals of macromolecules and macromolecular complexes as well as viruses, organelles, and cells.

Credit: European XFEL / Jan Hosan

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

Expanding horizons with a new instrument

Work is in full swing to construct the new European XFEL instrument SXP. Manuel Izquierdo, who is the Group Leader for SXP since December 2020, gave insights into how the instrument will expand the European XFEL portfolio, when it is set to begin operations and what his vision is for the instrument at this stage.

How would you describe the SXP instrument?

SXP stands for “Soft X-ray Port”. This name was chosen in keeping with the core idea of the project, that is, to provide the users an FEL beamline where they can temporarily set up their own experiment stations. And, this is what makes the instrument unique: users can bring and operate their own experiment stations. This will allow many techniques and experiments to be implemented. The successful proposals would be those that cannot be performed at the two soft X-ray instruments SCS or SQS. So basically, the idea is that the SXP instrument will expand the portfolio of techniques available to users at European XFEL.

What kind of experiments will be performed at SXP? 

In principle it is up to the user community to suggest. So far, three communities have contributed to the project. One community aims to use European XFEL as a laboratory for astrophysics, atomic physics, and fundamental research investigating highly charged ions. A second community proposed studies on chemical bond activation in biological reactions and inorganic catalysts. The third and biggest community aims to perform time and angle-resolved photoelectron spectroscopy experiments in solids. This technique will allow understanding the atomic structure, chemical, electronic and magnetic properties of materials. The counter part for atoms, molecules and clusters can be done at the SQS instrument.

Read more on the European XFEL website

Image: Panorama view of the SASE3 beamline, which feeds SQS and SCS, and will now include SXP

Credit: Photograph by Dirk Nolle (Copyright: DESY)

A clear path to better insights into biomolecules

An international team of scientists, led by Kartik Ayyer from the Max Planck Institute for the Structure and Dynamics of Matter, Germany, has obtained some of the sharpest possible 3D images of gold nanoparticles, and the results lay the foundation for getting high resolution images of macromolecules. The study was carried out at European XFEL’s Single Particles, Clusters, and Biomolecules & Serial Femtosecond Crystallography (SPB/SFX) instrument and the results have been published in Optica.

Carbohydrates, lipids, proteins, and nucleic acids, all of which populate our cells and are vital for life, are macromolecules. A key to understanding how these macromolecules work lies in learning the details about their structure. The team used gold nanoparticles, which acted as a substitute for biomolecules, measured 10 million diffraction patterns and used them to generate 3D images with record-breaking resolution. Gold particles scatter much more X-rays than bio-samples and so make good test specimens. They are able to provide lot more data and this is good for fine-tuning methods that can then be used on biomolecules.

Read more on the European XFEL website

Image: Illustration of 3D diffraction pattern of octahedral nanoparticles obtained by combining many snapshots after structural selection.

Credit: Kartik Ayyer and Joerg Harms, Max Planck Institute for the Structure and Dynamics of Matter

Controlling tiny magnetic swirls

Research on skyrmions may lead to more effective data storage

Skyrmions, commonly imagined as tiny magnetic swirls, are nanoscale magnetic quasi-particles that have recently become a hot topic because of their potential in the development of faster and more effective data storage devices.

For the first time, an international group of scientists, with lead scientists from the Massachusetts Institute of Technology, US, and the Max-Born-Institut in Berlin  have successfully been able to observe the formation of skyrmions in a magnetic material by using ultrashort laser pulses in a magnetic material, shedding light into the microscopic process and its time period. The X-ray pulses of the European XFEL’s revealed the creation of tiny skyrmion structures on nanometer length scales at a speed which is faster than previously thought possible. The results have been published in Nature Materials.

At the atomic level, magnetic materials resemble a sea of magnetic spins in either an ‘up’ or ‘down’ orientation. These spins are linked to each other so that a single spin change will affect the orientation of other spins. Skyrmions are tiny swirl-like structures where the center spin is oppositely aligned to the spins located at its boundary with a twisted spin configuration in between. These complex spin structures are very stable and small, making them interesting candidates for future spintronic devices. Spintronics exploits both the spin and the charge of electrons that could lower energy consumption in future memory devices and data storages.

Read more on the European XFEL website

Image: A laser pulse transforms a uniform magnetization (magnetization down everywhere) to a skyrmion swirl where the magnetization in the center points up. This transformation changes the so-called topology of the system.

Credit: B. Pfau, Max Born Institute

Accurate temperature snapshots

The first high energy density experiments pave way for future research

What does it take to accurately measure the temperature of a material which remains in a stable condition for just a fleeting nanosecond (one millionth of a second)? Consider using the high energy density (HED) instrument at European XFEL. And this is what an international team of researchers, with lead researchers from SLAC National Accelerator Laboratory, US, Oxford University, UK, and European XFEL, have done. Establishing methods to accurately measure temperatures in rapidly-evolving, transient systems is important for diverse purposes such as developing materials for spacecraft thermal shields, which face extreme changes in temperature and pressure when re-entering the Earth’s atmosphere, or in the study of the interior of giant planets such as Jupiter, Saturn, Uranus and Neptune. 

Read more on the European XFEL website

Image: Ulf Zastrau, Group Leader HED at the Experiment Station. Copyright: Jan Scholzel

First megahertz rate timing jitter observed

A report published today in the Journal Optica demonstrates accurate synchronisation of optical and X-ray lasers crucial for pump-probe experiments at XFEL. These snapshots taken during a reaction are stitched together to make molecular movies.

One of the ultimate goals for scientists using state-of-the-art X-ray free-electron lasers such as European XFEL is to be able to film the details of chemical and biological reactions. By stitching together a series of snapshots taken at different time intervals during a reaction, a molecular movie can be made of the process. So called pump-probe experiments use a precisely synchronised optical laser to trigger a reaction (the ‘pump’), while the X-ray laser takes a snapshot of the molecular structure at defined times during the reaction (the ‘probe’).

European XFEL now generates the ultrafast and ultra-intense light pulses needed to capture these processes that occur on extremely short timescales. The pulses of X-ray light generated by European XFEL are each less than a few millionths of a billionth of a second, or a few femtoseconds – fast enough to capture the series of events in a biological or chemical reaction. An accurate synchronization of the X-ray and optical laser pulses at these timescales is, however, challenging. Furthermore, tiny variations in the alignment and path travelled by the laser pulses caused, for example, by fluctuations in air pressure, or expansion in the electrical cables, have a relatively large impact on the accuracy of this experimental set-up. This variation is known as ‘timing jitter’. For pump-probe experiments to be successful, the jitter must be kept to a minimum, and be accurately characterized so that scientists can take it into account when assessing their data.

Read more on the European XFEL website

Image : The XPB/SFX instrument at European XFEL.

Credit: European XFEL / Jan Hosan

Day of Light: 60th anniversary of the laser

The invention of the laser 60 years ago has transformed science and everyday life.

Sixty years after the first laser was operated on 16 May 1960 by Theodore Maiman at Hughes Research Laboratories in California, lasers have revolutionized everyday life as well as science. Lasers are also fundamental for research at the European XFEL. A public event on the European XFEL campus planned to celebrate this anniversary has been postponed to a later date.

When the world’s biggest X-ray laser and one of the planet’s brightest light sources, the European XFEL, started operation in 2017, it was the culmination of several decades of scientific progress in laser and X-ray laser technology. Lasers operating in the visible wavelength range were invented in the 1960s. In these lasers, radiation is generated from electron transitions in atoms or molecules. The light emitted is then continuously amplified between mirrors. This makes it comparatively easy to produce high-quality laser light, and many applications now shape our everyday lives. Examples range from impressive light installations, to high precision surgical instruments, broadband telecommunication, components in the electrical devices we carry in our pockets, and the laser pointer we use during presentations.

Read more on the XFEL website

Image: The optical laser system for pump-probe experiments in the laser lab.

Credit: European XFEL / Jan Hosan

Super laser delivered to European XFEL

High Energy laser will enable study of exoplanet interiors.

A keenly awaited piece of high-tech equipment has been delivered to European XFEL. The high repetition rate, high-energy laser, DiPOLE 100-X, was developed in the UK by scientists and engineers at the Science and Technology Facilities Council’s Central Laser Facility (CFL) as part of the UK contribution to the facility. This unique laser, developed within the framework of the HiBEF user consortium, will be used at the instrument for High-Energy Density (HED) science at European XFEL to generate extreme temperatures and pressures in materials. The atomic structure and dynamics of these extreme states of materials can then be studied using the extremely bright and intense X-ray pulses produced by the European XFEL. This experimental set-up will enable scientists to create conditions similar to the interior of exoplanets with temperatures of up to 10,000°C, and pressures of up to 10,000 tons per square centimeter – similar to the weight of 2000 adult elephants concentrated onto the surface of a postage stamp!

>Read more on the European XFEL website

Image: The HED instrument at European XFEL.
Credit: European XFEL/Jan Hosan

Shaping attosecond waveforms

Scientists show how to control attosecond light pulses at a free-electron laser.

Chemical reactions and complex phenomena in liquids and solids are determined by the movement and rearrangement of electrons. These movements, however, occur on an extremely short timescale, typically only a few hundred attoseconds (1 attosecond =10-18 s or one quintillionth of a second).  Only light pulses of a comparable duration can be used to take snapshots of the dynamics of electrons. An international team of researchers led by Guiseppe Sansone from the University of Freiburg and including scientists from European XFEL have now, for the first time, been able to reliably generate, control and characterize such attosecond light pulses from a free-electron laser.

“These pulses enable us to study the first moment of the electronic response in a molecule or crystal,” explains Sansone. “With the ability to shape the electric field enables us to control electronic movements – with the long-term goal of optimising basic processes such as photosynthesis or charge separation in materials.”

>Read more on the European XFEL website

Image: Scientists have been able to shape the electric field of an attosecond light pulse.
Credit: Jürgen Oschwald and Carlo Callegari

Record participation at user meetings of the Hamburg research light sources

More than 1300 participants from 28 countries have registered

For this year’s users’ meetings of the Hamburg X-ray light sources, more participants have registered than ever before: More than 1300 scientists from 28 countries will come to discuss research with DESY’s X-ray source PETRA III, the free-electron laser in Hamburg FLASH and the X-ray laser European XFEL for three days starting this Wednesday. The jointly organised users’ meetings of DESY and European XFEL are the largest gathering of this kind worldwide.

“The steadily increasing number of participants from Germany and abroad shows the great importance of the Hamburg research light sources for the national and international scientific community,” says DESY’s Director for Photon Science, Edgar Weckert. “Hamburg is one of the X-ray capitals of the world.” The brilliant X-ray light from the powerful particle accelerators provides detailed insights into the structure and dynamics of matter at the atomic level. It can be used, for example, to decipher the structure of biomolecules, illuminate innovative materials, film chemical reactions and simulate and study the conditions inside planets and stars.

At the European X-ray laser European XFEL, all six scientific experiment stations are in operation since June. “Our users’ experiences and expertise are crucial for shaping the future of our science and facility”, says European XFEL managing director Robert Feidenhans’l. “The annual users’ meeting, therefore, is an extremely valuable opportunity for users and scientists who work at our facilities to share their experiences of doing experiments at the instruments, and talk about ideas for further development.” In 2019, 890 scientists from 255 institutes in 28 countries participated in experiments at the facility.

> Read more on the PETRA III and FLASH website

> Please find here another article on the European XFEL website

Picture: The jointly organised users’ meetings are the largest gathering of this kind worldwide.
Credit: DESY, Marta Mayer

First molecular movies at European XFEL

Scientists show how to use extremely short X-ray pulses to make the first movies of molecular processes at the European XFEL.

In a paper published today in Nature Methods, scientists show how to effectively use the high X-ray pulse repetition rate of the European XFEL to produce detailed molecular movies. This type of information can help us to better understand, for example, how a drug molecule reacts with proteins in a human cell, or how plant proteins store light energy.

Traditional structural biology methods use X-rays to produce snapshots of the 3D structure of molecules such as proteins. Although valuable, this information does not reveal details about the dynamics of biomolecular processes. If several snapshots can be taken in fast enough succession, however, these can be pasted together to make a so-called molecular movie. The high repetition rate of the extremely short X-ray pulses produced by the European XFEL makes it now possible to collect large amounts of data to produce movies with more frames than ever before. An international group of scientists have now worked out how to make optimal use of the European XFEL’s very high X-ray repetition rate to make these molecular movies at the facility in order to reveal unprecedented details of our world.

>Read more on the European XFEL website

Image: Artistic visualisation of a serial crystallography experiment. A stream of crystalline proteins are struck by an optical laser that initiates a reaction. Following a short delay the X-ray laser strikes the crystals. The information recorded about the arrangement of the atoms in the protein is used to reconstruct a model of the structure of the protein.
Credit: European XFEL / Blue Clay Studios

Using European XFEL to shed light on photosynthesis

First membrane protein studied at European XFEL

In a paper now published in Nature Communications an international group of scientists show that the fast X-ray pulse rate produced by the European XFEL can be used to study the structure of membrane proteins such as those involved in the process of photosynthesis. These results open up eagerly awaited experimental opportunities for scientists studying these types of proteins.

Large proteins and protein complexes are difficult to study with traditional structural biology approaches. Large protein complexes, such as those that sit across cell membranes and regulate traffic in and out of cells, are difficult to crystalize and generally only produce small crystals that are hard to analyse. The extremely fast X-ray pulses generated by European XFEL now enable scientists to collect large amounts of data from a stream of small crystals to develop detailed models of the 3D structure of these proteins.

>Read more on the European XFEL website

Image (extract, full illustration in the article): Graphic shows the basic design of a serial femtosecond crystallography experiment at European XFEL. X-ray bursts strike crystallized samples resulting in diffraction patterns that can be reassembled into detailed images.
Credit: Shireen Dooling for the Biodesign Institute at ASU

All SQS experiment stations up and running

Three new experiment stations expand the scientific possibilities in the field of soft X-ray science.

The soft X-ray instrument for Small Quantum Systems (SQS) welcomed its first users at the end of 2018. Now, almost a year later, the SQS team and collaborators have completed their ambitious plan to install and commission all three experiment stations, each specifically designed for different types of experiments and samples, ranging from atoms and small molecules to large clusters, nanoparticles and biomolecules. We look at how the instrument has developed during the past year, how important collaboration has been for the success of SQS so far, and what lies ahead.

>Read more on the European XFEL website

Image: SQS scientist Rebecca Boll makes final adjustments on the AQS experiment station before the first users arrive at the end of 2018.
Credit: European XFEL

Q&A with Sakura Pascarelli, new scientific director at European XFEL

European XFEL’s new scientific director talks about her career, her new role and her love for swimming.

On 1 September Sakura Pascarelli joined the European XFEL from the ESRF. In her role as scientific director she is responsible for the development of the four hard X-ray instruments. She spoke to Rosemary Wilson about her career, her new role and her love for swimming.

How did you get into science?

I spent part of my childhood in Burma and Indonesia. The American school system there enabled you to do lessons at your level, meaning you stayed interested and engaged. I really liked maths which I did with kids a few years older than me. I remember also doing experiments. I liked seeing things explode and break and try to understand why. Later on in Italy, I studied physics – not because I was particularly talented, but because I enjoyed it.

You joined ESRF at a time when the facility was still being built. What parallels can you see between that time, and now here at European XFEL?

I went to the ESRF to build one of the first beamlines there. We didn’t know what we would be able to discover or measure with this new machine. Here at European XFEL I see some of that same excitement. That opportunity taught me so much about instrumentation, and coordinating the construction of a beamline. But it is a different world now. Back then a good scientist with a solid background in physics, X-ray optics or instrumentation, could build a group and build a beamline. That is not possible here. This is so much more complicated. Here you need experts in X-rays, lasers, electronics, detectors. We don’t really know how to measure a femtosecond pulse let alone synchronise it with another laser! To run these instruments we need group leaders who are really good managers. This is so important. It is no longer enough for someone to be just a good scientist. At European XFEL we need to make sure the groups are well structured, well managed and that the people are happy. That might be difficult in the beginning when things don’t work, but when people see that their work is recognized, satisfaction and productivity increases.

>Read more on the European XFEL website

Image: European XFEL

Two years of user operation in numbers

1200 users, 60 experiments and 6 petabytes of data since operation began.

September 1 marks two years since the official opening and start of user operation at European XFEL. With the scheduled expansion from two to six operational instruments, the facility has expanded its experimental capacity and possibilities significantly during the past two years. At the same time, both the performance of the X-ray free-electron laser and instruments was continually improved. The scientific community shows strong interest in experiments at the new facility, with a total of 363 submitted proposals during this period, of which 98 were awarded beamtime. In total, 1200 users from across the world came to Schenefeld for their research. As the facility continues to be developed, even more time will be available for user experiments in the future.

>Read more on the European XFEL website

Image: Laser installation on the European XFEL campus in 2017 highlighting the five underground tunnels.
Credit: The European XFEL (Germany)