#SyncroLightAt75 – Structure of the Ribosome

Along with Ada Yonath and Thomas Steitz,Venkatraman Ramakrishnan from the MRC Laboratory of Molecular Biology in Cambridge, UK was awarded the 2009 Nobel Prize in Chemistry for determining the structure of the ribosome, one of the largest and most important molecules in the cell. X-ray crystallography experiments that enabled elucidation of the ribosome structure used synchrotron light from a number of light sources worldwide, each with unique capabilities, including the Swiss Light Source SLS.

Read more on the PSI website

Image: Interior view of the experimental hall at the Swiss Light Source SLS

Credit: Photo: H.R. Bramaz/PSI

#SynchroLightAt75 – From the Ribosome to CRISPR

Structural Biology at the ALS: From the Ribosome to CRISPR

Since the first protein crystallography beamline came online here in 1997, thousands of protein structures have been solved at the Advanced Light Source (ALS). One of the earliest high-profile structures was that of the full ribosome complex, where all the proteins necessary for life are produced based on RNA blueprints. The results reinforced the impression that the ribosome is a dynamic molecular machine with moving parts and a very complicated mechanism of action. More recently, the ALS has contributed to a greater understanding of programmable CRISPR proteins such as Cas9. In contrast to earlier genome-editing tools, Cas9 transforms the complicated and expensive process of gene editing into something simpler and more routine, like applying a genetic plug-in. In 2020, Jennifer Doudna and Emmanuelle Charpentier were awarded the Nobel Prize in Chemistry for “the development of a method for genome editing.”

Read more in the links below:

Publications:

J.H. Cate et al., Science 285, 2095 (1999)

M. Jinek et al., Science 343, 1247997 (2014)

Press release: The Nobel Prize in Chemistry 2020

ALS highlights:

Solving the Ribosome Puzzle
Intriguing DNA Editor (CAS9) Has a Structural Trigger

Jennifer Doudna and the Nobel Prize: The Advanced Light Source Perspective

#SynchroLightAt75 – Historical perspective of catalysis at Elettra

“Catalysis, is a strange principle of chemistry which works in ways more mysterious than almost any other of the many curious phenomena of science” New York Times: June 8, 1923

Heterogeneous catalysis is one of the most extensively studied functional systems since it is in the heart of chemical industry, fuel, energy production and storage and also is part in the devices for environmental protection.

The key processes in heterogeneous catalysis occur at dynamic reactant/catalyst surface interfaces. Since these processes involve coupling between different electronic, structural and mass transport events at time scales from fs to days, and space scales from nm to mm, we are still far from full comprehension how to design and control the catalysts performance. In this respect the ultrabright and tunable light, generated at the synchrotron facilities, has opened unique opportunities for using powerful spectroscopy, spectromicroscopy, scattering and imaging methods for exploring the morphology and chemical composition of complex catalytic systems at relevant length and time scales and correlate them to the fabrication or operating conditions.

The very demanded for catalysis studies is the surface sensitive PhotoElectron Spectroscopy (PES), based on the photoelectric effect, for which Einstein won the 1921 Nobel Prize in Physics, and demonstrated for the first time in 1957 by Kai Siegbahn who was awarded the Nobel Prize in 1981. PES has overcome its time and space limitations for studies of catalytic surface reactions thanks to the synchrotron light, which also added the opportunity for complementary use of X-ray absorption spectroscopy. At Elettra, the first time resolved PES studies with model metal catalyst systems were carried out at SuperESCA beamline in 1993 and few years later PES microscopy instruments, Scanning PhotoElelectron Microscope (SPEM) and X-ray PhotoElectron Emission Microscope (XPEEM) at ESCAMicroscopy and Nanospectroscopy beamlines have allowed for sub-mm space resolved studies, including imaging of dynamic surface mass transport processes as well.

Implementation in the last decade of operando experimental set-ups at APE, BACH and ESCAMicroscopy experimental stations for bridging the pressure gap of PES investigations has led to significant achievements in monitoring in-situ chemical, electrochemical and morphology evolution of all types catalytic systems under reaction conditions. Further complementary studies using X-ray absorption spectroscopy in photon-in/photon-out mode, ongoing at the XAFS and TwinMic beamlines are filling some remaining knowledge gaps for paving the road towards knowledge-based design and production of these complex and very desired functional materials.

M. Amati, L. Bonanni, L. Braglia, F. Genuzio, L. Gregoratti, M. Kiskinova, A. Kolmakov, A.Locatelli, E. Magnano, A. A. Matruglio, T. O. Menteş, S. Nappini, P. Torelli, P. Zeller,” Operando photoelectron emission spectroscopy and microscopy at Elettra soft X-ray beamlines: from model to real functional systems”, J. Electr. Spectr. Rel. Phenom. (2019) doi: 10.1016/j.elspec.2019.146902.

For first SUPERESCA – A. Baraldi, G. Comelli, S. Lizzit, M. Kiskinova, G. Paolucci “Real-Time X-Ray Photoelectron Spectroscopy of Surface Reactions” Surf. Sci. Reports 49, Nos. 6-8 (2003) 169.

For XPEEM A. Locatelli and M. Kiskinova “Imaging with Chemical Analysis: Adsorbed Structures Formed during Surface Chemical Reactions” A European Journal of Chemistry, 12 (2006) 8890.

Image: From model to real catalysts: structural and chemical complexity

#SynchroLightAt75 – Operation of the PAL-XFEL in 2020

After the PAL-XFEL was opened to the public in 2017, beamtime for user service has increased every year to provide more opportunities for user experiments. In 2020, 2,819 hours were provided for user beamtime out of the planned 2,910 hours and the beam availability was 96.9%. The provided beamtime of 2,819 hours was a significant increase from 2,409 hours in 2019, as shown in Table 1. To further increase beamtime, the PAL-XFEL has plans for 24-hour operation and simultaneous operation of hard and soft X-ray beamlines in the near future.

YearPlanned BeamtimeProvided BeamtimeAvailability
20182,012 h1,921 h95.5%
20192,503 h2,409 h96.2%
20202,910 h2,819 h96.9%
Table 1. Planned and provided beamtime in 2018, 2019, and 2020

FEL saturation of 0.062 nm (20 keV) was achieved for the first time in PAL-XFEL. The measured FEL energy using the e-loss scan was 408 uJ, the FEL radiation spectrum was 25.3 eV rms (0.127% of the center photon energy), and the FEL pulse duration (FWHM) was 11 fs, which corresponds to 1×1011 photons/pulse. The e-beam energy was 10.4 GeV and the undulator K was 1.4. The undulator gap scan was conducted for 20 undulators to check the FEL saturation as shown in Figure 1. Here, quadratic undulator tapering is applied for the last 6 undulators and the calculated gain length was 3.43 m.

Figure 1. Measurement results of the saturation curve at 20 keV photon energy

Two-color FEL generation with a single electron bunch has been successfully demonstrated for the hard X-ray undulator line, broadening the research capabilities at the PAL-XFEL. Test experiments have been conducted at two photon energies, 9.7 keV and 12.7 keV. A pump pulse is generated with 8 upstream undulators of the self-seeding section and a probe pulse is generated with 12 downstream undulators of the self-seeding section. The photon energies of the pulses can be independently controlled by changing the undulator parameter K and the time delay between two pulses can be controlled from 0 to 120 femtoseconds by using the magnetic chicane installed at the self-seeding section.

Figure 2. Intensity measurement results of two-color FEL generations.

Ultra-bright hard x-ray pulses using the self-seeded FEL were applied to the demonstration of serial femtosecond crystallography (SFX) experiments in 2020. We have consistently improved the spectral purity and peak of the self-seeded FEL using a laser heater and optimized crystal conditions over a hard x-ray range from 3.5 keV to 14.6 keV. The peak brightness for self-seeded hard x-ray pulses was enhanced to almost ten times greater than that of the SASE FEL over hard x-ray ranges. For example, the peak brightness of an x-ray at 9.7 keV is 3.2×1035 photons/(s·mm2·mrad2·0.1%BW), which is the highest peak brightness ever achieved for free-electron laser pulses. Thanks to the ultra-bright x-ray pulse with narrow bandwidth and superior spectral purity, SFX experiment results using the seeded FEL showed better data quality with high resolutions compared with that using the SASE FEL. This work has been published in Nature Photonics (https://doi.org/10.1038/s41566-021-00777-z).

Figure 3. Comparison of measured FEL intensity between SASE and self-seeding FEL.

#SynchroLightAt75 – APS lights the way to 2012 Chemistry Nobel

Thanks in part to research performed at the U.S. Department of Energy’s (DOE) Argonne National Laboratory, the 2012 Nobel Prize in Chemistry was awarded today to Americans Brian Kobilka and Robert Lefkowitz for their work on G-protein-coupled receptors.

G-protein-coupled receptors, or GPCRs, are a large family of proteins embedded in a cell’s membrane that sense molecules outside the cell and activate a cascade of different cellular processes in response. They constitute key components of how cells interact with their environments and are the target of nearly half of today’s pharmaceuticals.

These medicines work by connecting with many of the 800 or so human GPCRs. But to do this well, a drug needs to connect to the protein like a key opens a lock. Improving drugs requires knowing exactly how these proteins work and are structured, which is difficult because the long, slender protein chains are folded in an intricate pattern that threads in and out of the cell’s membrane.

In a study performed at Argonne in 2007, Kobilka, a professor at Stanford University, used intense X-rays produced by the laboratory’s Advanced Photon Source (APS) to make the first discovery of the structure of a human GPCR. This receptor, called the human β2 adrenoreceptor (β2AR), is responsible for a number of different biological responses, including facilitating breathing and dilating the arteries.

Read more on the Argonne National Laboratory website

Image: This is an image of a G-protein-coupled receptor signaling complex whose structure was identified in 2011. The receptor is in magenta while the different G protein subunits are colored green, red and blue. Stanford biochemist Brian Kobilka shared the 2012 Nobel Prize in Chemistry for his work in determining the structure of this activated GPCR using X-rays provided by Argonne’s Advanced Photon Source.

#SynchroLightAt75 – X-ray detector technology

X-Ray detectors first developed at Paul Scherrer Institute PSI in the 1990s to aid the search for the Higgs Boson at CERN and then applied to the Swiss Light Source SLS led to the spin-off, Dectris. Today this company employs over 100 people and its cutting-edge detectors are used at synchrotron and free electron laser (FEL) light sources worldwide for diverse applications ranging from protein structure determination to investigations into novel materials.

As the light source community marks #SynchroScienceAt75, we look back on this fascinating chapter in the history of light sources….

From the Higgs boson to new drugs (story published by PSI in 2016)

New ultrafast detector at the Paul Scherrer Institute

A picture-perfect example of how basic research makes solid contributions to the economy is the company DECTRIS in Baden-Dättwil, Switzerland — a spin-off of the Paul Scherrer Institute PSI, founded in 2006 and already highly successful. The detector that became, around ten years ago, the company’s founding product originated in the course of the search for the Higgs boson. Now the newest development from DECTRIS is on the market: an especially precise detector called EIGER, which is used for X-ray measurements at large research facilities. Since the fall of 2015, the newest model of the EIGER series has proven itself at the Swiss Light Source SLS. These days, researchers are writing the first scientific publications about experiments that have been carried out with the new detector. EIGER helps researchers to measure protein molecules better and more precisely than before. That in turn is of great interest for the development of new pharmaceuticals. It’s possible that urgently needed alternatives to antibiotics might be found in this way.

Read more on the PSI website

Image: PSI scientist Justyna Wojdyla and DECTRIS engineer Michel Stäuber with the EIGER X 16M – the spin-off company’s newest and, so far, highest-performance X-ray detector (caption from 2016)

Credit: Scanderbeg Sauer Photography

#SynchroLightAt75 – Rod MacKinnon’s Nobel Prize in chemistry

Rod MacKinnon – Nobel Prize in chemistry 2003 for work on the structure of ion channels  

The structural work of MacKinnon was carried out primarily at the Cornell High Energy Synchrotron Source (CHESS) and the National Synchrotron Light Source (NSLS) at Brookhaven. At the time, CHESS was a first-generation SR source.  The award for MacKinnon’s work was the second recognition of SR work by the Nobel Committee. MacKinnon acknowledges the crucial role that the two synchrotron facilities, Cornell Synchrotron (CHESS/MacCHESS) and NSLS, have played in his research on the protein crystallography of membrane channels.

He said, `Without exaggeration that most of what is known about the chemistry and structure of ion channels has come from experiments carried out at these SR centres’.

Rod MacKinnon

Read more on the Nobel Prize website

Image: View showing the location of CHESS, which is underground at Cornell

Credit: Jon Reis

#SynchroLightAt75 – The first multi-bend achromat synchrotron light source

At the end of the 1990’s, the MAX-lab management realized that it was necessary to start planning for a possible next step in the development of the laboratory. Although MAX II, one of the first 3rd generation light sources in the world and the flagship of the laboratory, had just recently come into operation, the long lead times made it necessary to start exploring possible further developments already at that stage. This is the saga of MAX IV Laboratory, the world’s first Multi-Bend Achromat (MBA) Synchrotron Radiation Light Source. MBAs strongly focus and guide electrons around the storage ring, creating an ultra-low emittance beam and therefore ultra-bright X-ray radiation.

Read more in this Nuclear Instruments and Methods in Physics Research – section A (NIM-A) publication

Image:  Prof. Ingolf Lindau, Director of MAX-lab 1991–97, shows the facility to the king of Sweden, Carl XVI Gustav, at the inauguration of MAX II, 15 September 1995

Credit:  MAX IV

#SynchroLightAt75 – Photon Factory at the dawn of structural biology using SR

The Photon Factory opened its first dedicated protein crystallography beamline with a Weissenberg camera in the mid-1980s. Prof. Ada Yonath, who was awarded the Nobel Prize in Chemistry in 2009 for her work on the structure-function analysis of ribosomes, was working at the Photon Factory at this time. The cryo-crystallography developed at the time led to the successful structural analysis.

Read more about the 2009 Nobel Prize in Chemistry and KEK’s Photon Factory here: KEK feature article

Image: Cryo-cooling system developed by Prof. Ada Yonath installed at the Photon Factory

Credit: Photo courtesy of Prof. Noriyoshi Sakabe

#SynchroLightAt75 – Development of the first in-vacuum undulator in the world

The development of in-vacuum undulators, in which a short period is achieved by placing periodic magnet inside the accelerator’s vacuum pipe, began at KEK around 1988, and light was successfully generated for the first time in December 1990.

This technology can transform synchrotron radiation facilities into compact and energy-saving ones, because short-period undulators can generate high energy and intense X-rays even in 3-GeV class storage ring. The development has led to a trend towards the construction of synchrotron radiation facilities installed in-vacuum undulators around the world.

To read more #SychroLightAt75 highlights, visit Highlights – Lightsources.org

Image: The first in-vacuum undulator (period length : 4cm)

Credit: Photon Factory, KEK

#SynchroLightAt75 campaign launches on International Day of Light

The SRS at Daresbury Laboratory in the UK was the world’s first dedicated synchrotron light source facility. It opened in 1980 and delivered worldwide impact and two Nobel Prizes.

The first of its kind, the SRS enabled research that has improved the quality of our lives in so many ways. This included research into diseases such as HIV and AIDS, as well as motor neurone disease, to name just a few examples. The structure of the Foot & Mouth virus was solved for the first time at the SRS – it was the first animal virus structure to be determined in Europe and led to the development of a vaccine. The huge magnetic memory of the Apple iPod was also the result of research carried out on the SRS. However, its most famous achievement was the key role it played towards a share of two Nobel Prizes in Chemistry.  One to Sir John Walker in 1997, for solving a structure of an enzyme that opened the way for new insights into metabolic diseases, and the other to Sir Venki Ramakrishnan in 2009, for his work on the structure and function of the Ribosome, the particle responsible for protein synthesis in living cells.

During its lifetime, the SRS created a critical mass of highly skilled engineers and technicians at Daresbury Laboratory, with specialisms ranging from detectors to magnets and electronics, and by the time it closed in 2008, it had collaborated with almost every country active in scientific research. It had hosted over 11,000 users from academia, government laboratories and industry worldwide, leading to the publication of more than 5000 research papers, resulting in numerous patents. The economic impact of this was vast on a worldwide scale, but it also played an important role in boosting the regional economy of the North West, having worked with hundreds of local businesses.

The success of the SRS led to the development of many similar machines around the world, with the technologies and skills developed still in use at many facilities today, including its UK successor, the Diamond Light Source at Harwell Science and Innovation Campus in Oxfordshire. It also led to the establishment of ASTeC, a leading centre for accelerator science and technology at Daresbury Laboratory, and the Cockcroft Institute, a joint venture between STFC and the Universities of Lancaster, Liverpool, Manchester and Strathclyde. It is also home to CLARA, a unique particle accelerator designed to develop, test and advance accelerator technologies of the future. Research carried out by accelerator scientists at Daresbury has had many impacts, particularly in the health and medicine arena, including work to develop our next generation of proton imaging technology for cancer detection, and research that could one day lead to more efficient diagnoses of cervical, oesophageal, and prostate cancers. In the footsteps of  senior scientist, Professor Ian Munro, who was responsible for the plan to build the SRS and for its operation at Daresbury, ASTeC’s accelerator scientists and engineers continue to play a key role in designing, building and upgrading the world’s newest generations of accelerator facilities.

Read more on the STFC/UKRI website

Image: The SRS control room


Credit: STFC