A citizen-science computer game for protein design

Using the computer game, “Foldit,” nonexpert citizen scientists designed new proteins whose structures, verified at the Advanced Light Source (ALS), were equivalent in quality to and more structurally diverse than computer-generated designs.

Proteins constitute the biomachinery—the cellular gears and levers—that make our bodies work. When this machinery is running smoothly, nutrients get absorbed, cells regenerate, and so on. When the machinery breaks down, the tools needed to fix the problem (i.e. drug molecules) are often proteins themselves.

Until recently, the pool of proteins available for such therapeutic purposes was limited to those found in nature. But natural proteins represent a small subset of all the possible ways to link 20 amino acids—the basic building blocks of all proteins—into chains hundreds, even thousands, of units long. On top of this, there are countless ways in which any given protein chain can fold—a key aspect of functionality.

In the last 20 years, “de novo” protein design (from scratch as opposed to starting with a known protein) has taken off, promising cheap and effective drugs with fewer side effects. But given the huge number of possibilities available, scientists are limited in their ability to fully explore this vast “protein space.”

>Read more on the Advanced Light Source website on Berkeley Lab

Image: The user interface of Foldit, a free online computer game developed to crowdsource problems in protein modeling. (a) The Foldit score: better models yield higher scores. (b) The design palette allows players to change the amino acids in the protein chain. (c) The “pull” tool allows players to manipulate the 3D structure of the model. (d) The “undo” graph tracks the score as a model is developed and allows players to backtrack. (e) Additional tool selections.

Study reveals ‘radical’ wrinkle in forming complex carbon molecules in space

Unique experiments at Berkeley Lab’s Advanced Light Source shine a light on a new pathway for carbon chemistry to evolve in space.

A team of scientists has discovered a new possible pathway toward forming carbon structures in space using a specialized chemical exploration technique at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab). The team’s research has now identified several avenues by which ringed molecules known as polycyclic aromatic hydrocarbons, or PAHs, can form in space. The latest study is a part of an ongoing effort to retrace the chemical steps leading to the formation of complex carbon-containing molecules in deep space. PAHs – which also occur on Earth in emissions and soot from the combustion of fossil fuels – could provide clues to the formation of life’s chemistry in space as precursors to interstellar nanoparticles. They are estimated to account for about 20 percent of all carbon in our galaxy, and they have the chemical building blocks needed to form 2D and 3D carbon structures.

>Read more on the ALS at Berkeley Lab website

Image: This composite image shows an illustration of a carbon-rich red giant star (middle) warming an exoplanet (bottom left) and an overlay of a newly found chemical pathway that could enable complex carbons to form near these stars.
Credits: ESO/L. Calçada; Berkeley Lab, Florida International University, and University of Hawaii at Manoa.

Particle accelerators drive decades of discoveries at Berkeley Lab and beyond

Berkeley Lab’s expertise in accelerator technologies has spiraled out from Ernest Lawrence’s earliest cyclotron to advanced compact accelerators.

Accelerators have been at the heart of the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) since its inception in 1931, and are still a driving force in the Laboratory’s mission and its R&D program. Ernest O. Lawrence’s invention of the cyclotron, the first circular particle accelerator – and the development of progressively larger versions – led him to build on the hillside overlooking the UC Berkeley campus that is now Berkeley Lab’s home. A variety of large cyclotrons are in use today around the world, and new accelerator technologies continue to drive progress.
“Our work in accelerators and related technologies has shaped the growth and diversification of Berkeley Lab over its long history, and remains a vital core competency today,” said James Symons, associate laboratory director for Berkeley Lab’s Physical Sciences Area.

>Read more on the ALS at Berkeley Lab website

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Tuning material properties with laser light

The research results suggest the possibility of creating microelectronic devices that use a laser beam to erase and rewrite bits of information in materials engineered for random-access memory and data storage.

Many semiconductor-based devices use electric currents to control and manipulate bits of information encoded into tiny magnetic domains. However, this approach is reaching the physical limits of thermally stable feature sizes, and scientists are actively searching for the next generation of materials and processes that could lead to smaller, faster, more powerful devices.
One possible path forward has been opened up by the emergence of materials that can be engineered, layer by layer, to theoretical specifications. Multiferroics, for example, are designed materials with technologically useful properties that can be controlled by external fields. While many studies have been performed on the effects of electric and magnetic fields on multiferroics, very few studies have explored the use of optical modulation (i.e., laser light) as a way to tune magnetic and electronic ordering in such materials.

>Read more on the Advanced Light Source at LBL website

Images: They are taken at the same illuminated region using PFM, PEEM with linearly polarized x-rays, and PEEM with circularly polarized x-rays. The strong black and white contrast in the linear dichroism image indicates the antiferromagnetic order; the red/blue contrast in the circular dichroism image shows the existence of ferromagnetic moments that lie parallel/antiparallel to the incident x-rays, respectively.

Research on how light-harvesting bacteria toggle off and on

The results could have long-range implications for artificial photosynthesis and optogenetics—the use of light to selectively activate biological processes.

Cyanobacteria are water-dwelling microbes capable of absorbing sunlight and converting it into chemical energy through photosynthesis. Long ago, ancient versions of these bacteria were incorporated into plant cells, where they eventually evolved into chloroplasts, the organelles responsible for carrying out photosynthesis in green plants. Today, in seeking to develop artificial photosynthesis to harness the sun’s abundant energy, scientists look to cyanobacteria to better understand the nuts and bolts of how natural photosynthesis works.

Cyanobacterial “off switch”

One topic of interest is how cyanobacteria respond to too much light. If a sunlight-harvesting system becomes overloaded with absorbed solar energy, it most likely will suffer some form of damage. Nature has solved the problem in cyanobacteria through a protective mechanism—an energy-quenching “off switch” in which excess solar energy is safely dissipated as heat.

>Read more on the Advanced Light Source at BNL

Illustration: X-ray footprinting provides time-resolved information about where key conformational changes occur. On the left is the overall OCP structure. The two structures on the right highlight local areas with increasing protein packing over time (blue shading) and areas with decreasing protein packing over time (red shading). The changes in accessibility are initiated by the movement of the carotenoid molecule (magenta chain).

Natural defense against red tide toxin found in bullfrogs

A team led by Berkeley Lab faculty biochemist Daniel Minor has discovered how a protein produced by bullfrogs binds to and inhibits the action of saxitoxin, the deadly neurotoxin made by cyanobacteria and dinoflagellates that causes paralytic shellfish poisoning.
The findings, published this week in Science Advances, could lead to the first-ever antidote for the compound, which blocks nerve signaling in animal muscles, causing death by asphyxiation when consumed in sufficient quantities.
“Saxitoxin is among the most lethal natural poisons and is the only marine toxin that has been declared a chemical weapon,” said Minor, who is also a professor at the UCSF Cardiovascular Research Institute. About one thousand times more potent than cyanide, saxitoxin accumulates in tissues and can therefore work its way up the food chain – from the shellfish that eat the microbes to fish, turtles, marine mammals, and us.

>Read more on the ALS website

Image: A photo illustration showing the atomic structures of saxiphilin and saxitoxin, a red tide algal bloom, and an American bullfrog (R. catesbeiana).
Credit: Daniel L. Minor, Jr., and Deborah Stalford/Berkeley Lab.

Catalyst improves cycling life of magnesium/sulfur batteries

Comprising earth-abundant elements, cathodes made of magnesium/sulfur compounds could represent the next step in battery technology. However, despite being dendrite free and having a high theoretical energy density compared with lithium batteries, magnesium/sulfur batteries have suffered from high polarization and extremely limited recharging capabilities. To gain electrochemical insights into magnesium/sulfur batteries during charge–discharge cycles, researchers used the Advanced Light Source (ALS) to investigate and optimize battery chemistry.

The in situ x-ray absorption spectroscopy (XAS) capabilities at ALS Beamlines 5.3.1 and 10.3.2 provided information on the oxidation state of sulfur under real operating conditions. The group found that the conversion of sulfur in the first discharging process was divided into three stages: formation of MgSand MgSat a fast reaction rate, reduction of MgSto Mg3S8, and a sluggish further reduction of Mg3Sto MgS. The in situ XAS analysis revealed that Mg3Sand MgS are more electrochemically inert and cannot revert to the active forms of sulfur, thereby dramatically reducing the battery’s cycling life.

>Read more on the ALS website

Image: Efforts to develop magnesium/sulfur batteries have been stymied by a loss of capacity after the first discharging process. In situ XAS revealed the accumulation of Mg3S8 and MgS during the discharging process, which are inert forms of the magnesium/sulfur compounds. Introducing a titanium-sulfide catalyst activated the compounds, reversing the chemical mechanism so that the battery could be recharged multiple times.

 

Electric dipoles form chiral skyrmions

Control of such phenomena could one day lead to low-power, nonvolatile data storage as well as to high-performance computers.

A group of researchers, led by scientists from Berkeley Lab’s Materials Sciences Division and UC Berkeley’s Materials Science and Engineering Department, set out to find ways to control how heat moves through materials. They fabricated a material with alternating layers of strontium titanate, which is an electrical insulator, and lead titanate, a ferroelectric material with a natural electrical polarization that can be reversed by the application of an external electric field.

When the group took the material to Berkeley Lab’s Molecular Foundry for atomic-resolution scanning transmission electron microscope (STEM) measurements, however, they found something completely unexpected: bubble-like formations had appeared throughout the material, even at room temperature.

>Read more on the ALS website

Image: (a) Hard x-ray studies showed the presence of two sets of ordering: regular peaks along the out-of-plane direction (Qz), related to superlattice periodicity (about 12 nm), and satellite peaks in the in-plane direction (Qy), corresponding to the in-plane skyrmion periodicity (about 8 nm). (b) RSXD studies were performed at the in-plane satellite peaks, which correspond to the periodic polarization texture of the skyrmions’ Bloch components. (c) Spectra from a satellite peak for right- (red) and left- (blue) circularly polarized light. (d) The same spectra with background fluorescence subtracted. (e) The difference spectrum shows a clear circular dichroism peak at the titanium L3 t2g edge.

‘A day in the light’ Videos highlight how scientists use light in experiment

In recognition of the International Day of Light (@IDL2019) on May 16, the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) is highlighting how scientists use light in laboratory experiments. From nanolasers and X-ray beams to artificial photosynthesis and optical electronics, Berkeley Lab researchers tap into light’s many properties to drive a range of innovative R&D.
In the three videos displayed below, you will learn how light drives the science of Berkeley Lab’s Advanced Light Source (ALS), a synchrotron that produces many forms of light beams. These light beams are customized to perform a variety of experimental techniques for dozens of simultaneous experiments conducted by researchers from across the nation and around the world.

> Read more on the Advanced Light Source at Berkley Lab website

Image: Shambhavi Pratap, ALS Doctoral Fellow in Residence and a Ph.D. student at the Technical University of Munich, discusses how she studies thin-film solar energy materials using X-rays at the ALS.
Credit: Marilyn Chung/Berkeley Lab

 

Research on sand near Hiroshima shows fallout debris from A-Bomb blast

X-ray studies at Berkeley Lab provide evidence for source of exotic assortment of melt debris

Mario Wannier, a career geologist with expertise in studying tiny marine life, was methodically sorting through particles in samples of beach sand from Japan’s Motoujina Peninsula when he spotted something unexpected: a number of tiny, glassy spheres and other unusual objects.
Wannier, who is now retired, had been comparing biological debris in beach sands from different areas in an effort to gauge the health of local and regional marine ecosystems. The work involved examining each sand particle in a sample under a microscope, and with a fine brush, separating particles of interest from grains of sediment into a tray for further study.

>Read more on the Advanced LIght Source at L. Berkeley Lab website

Image: Researchers collected and studied beach sands from locations near Hiroshima including Japan’s Miyajima Island, home to this torii gate, which at high tide is surrounded by water. The torii and associated Itsukushima Shinto Shrine, near the city of Hiroshima, are popular tourist attractions. The sand samples contained a unique collection of particles, including several that were studied at Berkeley Lab and UC Berkeley.
Credit: Ajay Suresh/Wikimedia Commons

Superconductor exhibits “glassy” electronic phase

The study provides valuable insight into the nature of collective electron behaviors and how they relate to high-temperature superconductivity.

At extremely low temperatures, superconductors conduct electricity without resistance, a characteristic that’s already being used in cryogenically cooled power lines and quantum-computer prototypes. To apply this characteristic more widely, however, it’s necessary to raise the temperature at which materials become superconducting. Unfortunately, the exact mechanism by which this happens remains unclear.

Recently, scientists found that electrons in cuprate superconductors can self-organize into charge-density waves—periodic modulations in electron density that hinder the flow of electrons. As this effect is antagonistic to superconductivity, tremendous effort has been devoted to fully characterizing this charge-order phase and its interplay with high-temperature superconductivity.

>Read more on the Advanced Light Source at L. Berkeley Lab website

Image: At low doping levels, the charge correlations in the copper–oxide plane possess full rotational symmetry (Cinf) in reciprocal space (left), in marked contrast to all previous reports of bond-oriented charge order in cuprates. In real space (right), this corresponds to a “glassy” state with an apparent tendency to periodic ordering, but without any preference in orientation (scale bar ~5 unit cells).

Electric skyrmions charge ahead for next-generation data storage

Berkeley Lab-led research team makes a chiral skyrmion crystal with electric properties; puts new spin on future information storage applications.

When you toss a ball, what hand do you use? Left-handed people naturally throw with their left hand, and right-handed people with their right. This natural preference for one side versus the other is called handedness, and can be seen almost everywhere – from a glucose molecule whose atomic structure leans left, to a dog who shakes “hands” only with her right.

Handedness can be exhibited in chirality – where two objects, like a pair of gloves, can be mirror images of each other but cannot be superimposed on one another. Now a team of researchers led by Berkeley Lab has observed chirality for the first time in polar skyrmions – quasiparticles akin to tiny magnetic swirls – in a material with reversible electrical properties. The combination of polar skyrmions and these electrical properties could one day lead to applications such as more powerful data storage devices that continue to hold information – even after a device has been powered off. Their findings were reported this week in the journal Nature.

>Read more on the Advanced Light Source website

Image: Simulations of skyrmion bubbles and elongated skyrmions for the lead titanate/strontium titanate superlattice.
Credit: Berkeley Lab.

A new twist in soft x-ray beams

Light waves, when generated a certain way, can exert twisting forces on matter. In the visible-light regime, such beams have been used as “optical tweezers” to trap and manipulate tiny particles (like a tractor beam) or to detect rotational motion in targets. Now, the ability to generate beams with a specific type of rotational character, known as orbital angular momentum (OAM), has been extended to the soft x-ray regime. The work lays the foundation for a new type of soft x-ray contrast mechanism that could provide access to previously hidden material properties.
In a recently published Nature Photonics paper, researchers from the Advanced Light Source (ALS) and the University of Oregon reported on the fabrication and testing of specialized diffraction gratings that, when placed in the coherent light of ALS Beamline 12.0.2, produce OAM soft x-ray beams of exceptionally high quality.

>Read more on the Advanced Light Source website

Image: A  flower-like interference pattern generated by a special diffraction grating that superposes two different orbital angular momentum (OAM) modes on a soft x-ray beam.

Absorber captures excess chemotherapy drugs

The work opens up a new route to fighting cancer that minimizes drug toxicity and enables personalized, targeted, high-dose chemotherapy.

Most anticancer drugs are poisonous, so doctors walk a delicate line when administering chemotherapy. A dose must be sufficient to kill or stop the growth of cancer cells in the target organ, but not high enough to irreparably damage a patient’s other organs. To avoid this, doctors can thread catheters through the bloodstream to deliver chemotherapy drugs directly to the site of the tumor—a method known as intra-arterial chemotherapy. Still, typically more than half of the dose injected into the body escapes the target organ. Several years ago, researchers began working on a major improvement: placing a device “downstream” of the targeted organ to filter out excess chemo so that much less of the drug reaches the body as a whole.

>Read more on the Advanced Light Source

Image: (extract, see here the full image)
(a) Diagram of the proposed approach for drug capture using a 3D-printed cylindrical absorber. (b) Chemical structure of doxorubicin, the chemotherapy drug used in this study. (c) Schematic of the endovascular treatment of liver cancer. Excess drug molecules are captured by the absorber in the vein draining the organ. An introducer sheath guides the absorber to the desired location via a guide wire.

The best topological conductor yet: spiraling crystal is the key to exotic discovery

X-ray research at Berkeley Lab reveals samples are a new state of matter

The realization of so-called topological materials – which exhibit exotic, defect-resistant properties and are expected to have applications in electronics, optics, quantum computing, and other fields – has opened up a new realm in materials discovery.
Several of the hotly studied topological materials to date are known as topological insulators. Their surfaces are expected to conduct electricity with very little resistance, somewhat akin to superconductors but without the need for incredibly chilly temperatures, while their interiors – the so-called “bulk” of the material – do not conduct current.
Now, a team of researchers working at the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) has discovered the strongest topological conductor yet, in the form of thin crystal samples that have a spiral-staircase structure. The team’s study of crystals, dubbed topological chiral crystals, is reported in the March 20 edition of the journal Nature.

>Read more on the ALS at Berkeley Lab website

Image: This illustration shows a repeated 2D patterning of a property related to electrical conductivity, known as the surface Fermi arc, in rhodium-silicon crystal samples.
Credit: Hasan Lab/Princeton University

Reversible lattice-oxygen reactions in batteries

The results open up new ways to explore how to pack more energy into batteries with electrodes made out of low-cost, common materials.

For a wide range of applications, from mobile phones to electric vehicles, the reversibility and cyclability of the chemical reactions occurring inside a rechargeable battery are key to commercial viability. Conventional wisdom had held that involving oxygen in a battery’s electrochemical operation spontaneously triggers irreversible oxygen losses and parasitic surface reactions, reducing reversibility and safety. Recently however, the idea emerged that reactions involving lattice oxygen (i.e., oxygen that’s part of the crystal-lattice structure vs oxygen on the surface) could be useful for improving battery capacity. Here, researchers report the first direct quantification of a strong, beneficial, and highly reversible chemical reaction involving lattice oxygen in electrodes made with low-cost elements.

>Read more on the Advanced Light Source

Image: Advanced spectroscopy at the ALS clearly resolves the activities of cations and anions (known in Chinese as “yin” and “yang” ions) in battery electrodes.