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How to catch a molecule

With a nano-ring-based toroidal trap, cold polar molecules near the gray shaded surface approaching the central region may be trapped within a nanometer-scale volume (credit: ORNL)

In a paper published in Physical Review A, Oak Ridge National Laboratory and University of Tennessee physicists describe conceptually how they may be able to trap and exploit a molecule’s energy to advance a number of fields.

“A single molecule has many degrees of freedom, or ways of expressing its energy and dynamics, including vibrations, rotations and translations,” said Ali Passian of Oak Ridge National Lab. “For years, physicists have searched for ways to take advantage of these molecular states, including how they could be used in high-precision instruments or as an information storage device for applications such as quantum computing.”

It’s a trap!

Catching a molecule with minimal disturbance is not an easy task, considering its size — about 1 nanometer — but this paper proposes a method that may overcome that obstacle.

When interacting with laser light, the ring toroidal nanostructure can trap the slower molecules at its center. That’s because the nano-trap, which can be made of gold using conventional nanofabrication techniques, creates a highly localized force field surrounding the molecules. The team envisions using scanning probe microscopy techniques, which can measure extremely small forces, to access individual nano-traps.

“Once trapped, we can interrogate the molecules for their spectroscopic and electromagnetic properties and study them in isolation without disturbance from the neighboring molecules,” Passian said.

Previous demonstrations of trapping molecules have relied on large systems to confine charged particles such as single ions. Next, the researchers plan to build actual nanotraps and conduct experiments to determine the feasibility of fabricating a large number of traps on a single chip.

“If successful, these experiments could help enable information storage and processing devices that greatly exceed what we have today, thus bringing us closer to the realization of quantum computers,” Passian said.

Abstract of Toroidal nanotraps for cold polar molecules

Electronic excitations in metallic nanoparticles in the optical regime that have been of great importance in surface-enhanced spectroscopy and emerging applications of molecular plasmonics, due to control and confinement of electromagnetic energy, may also be of potential to control the motion of nanoparticles and molecules. Here, we propose a concept for trapping polarizable particles and molecules using toroidal metallic nanoparticles. Specifically, gold nanorings are investigated for their scattering properties and field distribution to computationally show that the response of these optically resonant particles to incident photons permit the formation of a nanoscale trap when proper aspect ratio, photon wavelength, and polarization are considered. However, interestingly the resonant plasmonic response of the nanoring is shown to be detrimental to the trap formation. The results are in good agreement with analytic calculations in the quasistatic limit within the first-order perturbation of the scalar electric potential. The possibility of extending the single nanoring trapping properties to two-dimensional arrays of nanorings is suggested by obtaining the field distribution of nanoring dimers and trimers.

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‘Tree of life’ for 2.3 million species released

This circular family tree of Earth’s lifeforms is considered a first draft of the 3.5-billion-year history of how life evolved and diverged (credit: Duke University)

A first draft of the “tree of life” for the roughly 2.3 million named species of animals, plants, fungi and microbes — from platypuses to puffballs — has been released.

A collaborative effort among eleven institutions, the tree depicts the relationships among living things as they diverged from one another over time, tracing back to the beginning of life on Earth more than 3.5 billion years ago.

Tens of thousands of smaller trees have been published over the years for select branches of the tree of life — some containing upwards of 100,000 species — but this is the first time those results have been combined into a single tree that encompasses all of life.

“This is the first real attempt to connect the dots and put it all together,” said principal investigator Karen Cranston of Duke University. “Think of it as Version 1.0.” The current version of the tree — along with the underlying data and source code — is available to browse, edit, and download free at https://tree.opentreeoflife.org — a sort of “Wikipedia” for the evolutionary trees.

It is also described in an open-access article appearing Sept. 18 in the Proceedings of the National Academy of Sciences.

Uses of evolutionary trees

Open Tree of Life workflow (credit: Cody E. Hinchliff et al./PNAS)

Understanding how the millions of species on Earth are related to one another helps scientists discover new drugs, increase crop and livestock yields, and trace the origins and spread of infectious diseases such as HIV, Ebola and influenza, the scientists say.

The researchers pieced it together by compiling thousands of smaller chunks that had already been published online and merging them together into a gigantic “supertree” that encompasses all named species. The initial draft is based on nearly 500 smaller trees from previously published studies.

To map trees from different sources to the branches and twigs of a single supertree, one of the biggest challenges was simply accounting for the name changes, alternate names, common misspellings and abbreviations for each species. The eastern red bat, for example, is often listed under two scientific names, Lasiurus borealis and Nycteris borealis. Spiny anteaters once shared their scientific name with a group of moray eels.

“Although a massive undertaking in its own right, this draft tree of life represents only a first step,” the researchers wrote. For one, only a tiny fraction of published trees are digitally available.

A survey of more than 7,500 phylogenetic studies published between 2000 and 2012 in more than 100 journals found that only one out of six studies had deposited their data in a digital, downloadable format that the researchers could use.

The vast majority of evolutionary trees are published as PDFs and other image files that are impossible to enter into a database or merge with other trees.

As a result, the relationships depicted in some parts of the tree, such as the branches representing the pea and sunflower families, don’t always agree with expert opinion.

Other parts of the tree, particularly insects and microbes, remain elusive. That’s because even the most popular online archive of raw genetic sequences — from which many evolutionary trees are built — contains DNA data for less than five percent of the tens of millions species estimated to exist on Earth.

“As important as showing what we do know about relationships, this first tree of life is also important in revealing what we don’t know,” said co-author Douglas Soltis of the University of Florida.

To help fill in the gaps, the team is also developing software that will enable researchers to log on and update and revise the tree as new data come in for the millions of species still being named or discovered.

“It’s by no means finished,” Cranston said. “It’s critically important to share data for already-published and newly-published work if we want to improve the tree.”

“Twenty five years ago people said this goal of huge trees was impossible,” Soltis said. “The Open Tree of Life is an important starting point that other investigators can now refine and improve for decades to come.”

Abstract of Synthesis of phylogeny and taxonomy into a comprehensive tree of life

Reconstructing the phylogenetic relationships that unite all lineages (the tree of life) is a grand challenge. The paucity of homologous character data across disparately related lineages currently renders direct phylogenetic inference untenable. To reconstruct a comprehensive tree of life, we therefore synthesized published phylogenies, together with taxonomic classifications for taxa never incorporated into a phylogeny. We present a draft tree containing 2.3 million tips—the Open Tree of Life. Realization of this tree required the assembly of two additional community resources: (i) a comprehensive global reference taxonomy and (ii) a database of published phylogenetic trees mapped to this taxonomy. Our open source framework facilitates community comment and contribution, enabling the tree to be continuously updated when new phylogenetic and taxonomic data become digitally available. Although data coverage and phylogenetic conflict across the Open Tree of Life illuminate gaps in both the underlying data available for phylogenetic reconstruction and the publication of trees as digital objects, the tree provides a compelling starting point for community contribution. This comprehensive tree will fuel fundamental research on the nature of biological diversity, ultimately providing up-to-date phylogenies for downstream applications in comparative biology, ecology, conservation biology, climate change, agriculture, and genomics.

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A thermal invisibility cloak that actively redirects heat

Active thermal cloak hides a circular object in conductive heat flow by “pumping” heat from hot end to cold end (credit: Xu & Zhang/NTU)

A new thermal cloak that can render an object thermally invisible by actively redirecting incident heat has been developed by scientists at the Nanyang Technological University (NTU) in Singapore. It’s similar to how optical invisibility cloaks can bend and diffract light to shield an object from sight and specially fabricated acoustic metamaterials can hide an object from sound waves.

The system has the potential to fine-tune temperature distribution and heat flow in electronic and semiconductor systems for applications that require efficient heat dissipation (cooling) and homogenous (even) thermal expansion, such as high-power engines, magnetic resonance imaging (MRI) instruments, thermal sensors, and clothing, said Prof. Baile Zhang of NTU.

Zhang and colleagues previously designed a metamaterial thermal cloak that passively guided conductive heat around a hidden object, with no way to control heat flow and direction. The researchers decided to look into controlling thermal cloaking electrically by actively “pumping” heat from one side of the hidden object to the other side, using thermoelectric modules, as described in an open-access paper and on the cover of Applied Physics Letters, from AIP Publishing.

Building the thermal cloak

Design of active thermal cloak. (a) Multiple thermoelectic components are arranged around the air hole with equal distance on the Carbon Steel plate. Blue components absorb incident thermal flux while red ones release heat back to the plate. (b) The side view of the marked region in (a), illustrating the working mechanism of TE components when functioning as heat absorber/emitter. An applied voltage causes a directional motion of charge carriers in positive/negative blocks, resulting in a heat flux in the designed direction. The bottom/top orange arrow indicates the absorption/release of heat by TE components. The dashed arrow indicates the heat transfer through a constant-temperature heat “reservoir” which is a large copper bulk in the experiment. (credit: Dang Minh Nguyen et al./Applied Physics Letters)

To construct their active thermal cloak, the researchers deployed 24 small thermoelectric modules, which are semiconductor heat pumps controlled by an external input voltage, around a 62-millimeter diameter air hole in a carbon steel plate just 5 mm thick. The modules operate via the Peltier effect, in which a current running through the junction between two conductors can remove or generate heat.

When many modules are attached in series, they can redirect heat flow. The researchers attached the bottom and top ends of the modules to hot and cold surfaces at 60° C and 0° C respectively to generate diffusive heat flux.

When the researchers applied a variety of specific voltages to each of the 24 modules, the heat falling on the hot-surface side of the air hole was absorbed and delivered to a constant-temperature copper heat reservoir attached to the modules. The modules on the cold-surface side released the same amount of heat from the reservoir into the steel plate. This prevented heat from diffusing through the air hole, a technique, the researchers say, that can be used to shield sensitive electronic components from heat dissipation.

The researchers found that their active thermal cloaking was not limited by the shape of the object being hidden.

Zhang and his colleagues plan to apply the thermal cloaks in electronic systems, improve the efficiency of heat transfer, and develop an intelligent control system for the cloak.

Abstract of Active thermal cloak

Thermal cloaking, as an ultimate thermal “illusion” phenomenon, is the result of advanced heat manipulation with thermal metamaterials—heat can be guided around a hidden object smoothly without disturbing the ambient thermal environment. However, all previous thermal metamaterial cloaks were passive devices, lacking the functionality of switching on/off and the flexibility of changing geometries. In this letter, we report an active thermal cloaking device that is controllable. Different from previous thermal cloaking approaches, this thermal cloak adopts active thermoelectric components to “pump” heat from one side to the other side of the hidden object, in a process controlled by input electric voltages. Our work not only incorporates active components in thermal cloaking but also provides controllable functionality in thermal metamaterials that can be used to construct more flexible thermal devices.

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Transparent photonic coating cools solar cells to boost efficiency

Stanford engineers have invented a transparent material that improves the efficiency of solar cells by radiating thermal energy (heat) into space (credit: Stanford Engineering)

Stanford engineers have developed a transparent material that improves the efficiency of solar cells by radiating thermal energy (heat) into space, even in full sunlight.

The invention may solve a longstanding problem for the solar industry: the hotter solar cells become, the less efficient they are at converting sunlight to electricity. The Stanford solution is based on a thin, patterned silica material laid on top of a traditional solar cell. The material is transparent to the visible sunlight that powers solar cells, but captures and emits thermal radiation, or heat, cooling the solar cell and thus allowing it to convert more photons into electricity.

The work by Shanhui Fan, a professor of electrical engineering at Stanford, research associate Aaswath P. Raman and doctoral candidate Linxiao Zhu is described in the current issue of Proceedings of the National Academy of Sciences.

The same inventors previously developed an ultrathin material, covered on KurzweilAI, that radiated infrared light (in the thermal “long” infrared atmospheric transparency window of ~7 to 30 microns) from the Sun directly back toward space without warming the atmosphere (thus avoiding the greenhouse effect). They presented that work in Nature, describing it as “radiative cooling” because it shunted thermal energy directly into the deep, cold void of space. It was specifically intended for cooling buildings.

A silica photonic crystal radiator

In their new paper, the researchers applied that work to improve solar array performance.

Silica photonic crystal radiates far-infrared light (heat) into space (credit: Linxiao Zhu et al./PNAS)

The Stanford team tested their technology on a custom-made solar absorber — a device that mimics the properties of a solar cell without producing electricity — covered with a silica photonic crystal (a micrometer-scale pattern) designed to maximize the capability to dump heat, in the form of infrared light (in 8 to 30 microns range) into space. Their experiments showed that the overlay allowed visible light to pass through to the solar cells, but that the pattern also cooled the underlying absorber by as much as 23 degrees Fahrenheit.

For a typical crystalline silicon solar cell with an efficiency of 20 percent, 23 F of cooling would improve absolute cell efficiency by more than 1 percent, a figure that represents a significant gain in energy production.

The researchers said the new transparent thermal overlays work best in dry, clear environments, which are also preferred sites for large solar arrays. They believe they can scale things up so that commercial and industrial applications are feasible, perhaps using nanoprint lithography, which is a common technique for producing nanometer-scale patterns.

Cooler cars

Zhu said the technology has significant potential for any outdoor device or system that demands cooling but requires the preservation of the visible spectrum of sunlight for either practical or aesthetic reasons.

“Say you have a car that is bright red,” Zhu said. “You really like that color, but you’d also like to take advantage of anything that could aid in cooling your vehicle during hot days. Thermal overlays can help with passive cooling, but it’s a problem if they’re not fully transparent.” That’s because the perception of color requires objects to reflect visible light, so any overlay would need to be transparent, or else tuned such that it would absorb only light outside the visible spectrum.

“Our photonic crystal thermal overlay optimizes use of the thermal portions of the electromagnetic spectrum without affecting visible light,” Zhu said, “so you can radiate heat efficiently without affecting color.”

Abstract of Radiative cooling of solar absorbers using a visibly transparent photonic crystal thermal blackbody

A solar absorber, under the sun, is heated up by sunlight. In many applications, including solar cells and outdoor structures, the absorption of sunlight is intrinsic for either operational or aesthetic considerations, but the resulting heating is undesirable. Because a solar absorber by necessity faces the sky, it also naturally has radiative access to the coldness of the universe. Therefore, in these applications it would be very attractive to directly use the sky as a heat sink while preserving solar absorption properties. Here we experimentally demonstrate a visibly transparent thermal blackbody, based on a silica photonic crystal. When placed on a silicon absorber under sunlight, such a blackbody preserves or even slightly enhances sunlight absorption, but reduces the temperature of the underlying silicon absorber by as much as 13°C due to radiative cooling. Our work shows that the concept of radiative cooling can be used in combination with the utilization of sunlight, enabling new technological capabilities.

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Massive clash of black holes raises astronomers’ hopes of witnessing gravitational waves

Artist’s conception of converging supermassive black holes in the Virgo constellation (credit: P. Marenfeld/NOAO/AURA/NSF)

Circling like prizefighters in a ring, a pair of supermassive black holes is heading toward an epic collision. One so powerful it would send a burst of gravitational waves surging through and distorting the very fabric of space-time.

Already, the intensity of the encounter is causing mysterious rhythmic flashes of light coming from quasar PG 1302-102 — 3.5 billion light-years away in the Virgo constellation.

“This is the closest we’ve come to observing two black holes on their way to a massive collision,” said Columbia University astronomer Zoltan Haiman in a new study in the journal Nature.

“Watching this process reach its culmination [confirming the existence of a binary black hole in the relativistic regime by measuring optical and UV brightness] can tell us whether black holes and galaxies grow at the same rate, and ultimately test* a fundamental property of space-time: its ability to carry vibrations called gravitational waves, produced in the last, most violent, stage of the merger.”

The ultimate crash

They estimated the combined and relative mass of PG 1302-102’s black holes, allowing them to narrow down the pair’s predicted crash time: about 100,000 years.

Meanwhile, a recent uptick in the number of black hole binary discoveries has made astronomers hopeful they may in fact witness an actual collision in the next decade and therefore detect gravitational waves, said study coauthor David Schiminovich, also an astronomer at Columbia.

Such a detection would let them “probe the secrets of gravity and test Einstein’s theory in the most extreme environment in our universe — black holes,” said the study’s lead author, Daniel D’Orazio, a graduate student at Columbia. “Getting there is a holy grail of our field.”

* The hope of doing such a test has energized astronomers. Previously, a team led by Matthew Graham, a computational astronomer at the California Institute of Technology, designed an algorithm to pick out repeating light signals from 247,000 quasars monitored by telescopes in Arizona and Australia. Of the 20 pairs of black hole candidates discovered, they focused on the bright quasar. In a January study in Nature, they showed that PG 1302-102 appeared to brighten by 14 percent every five years, indicating the pair was less than a tenth of a light-year apart.

Intrigued, Haiman and his colleagues wondered if they could build a theoretical model to explain the repeating signal. If the black holes were as close as predicted, one had to be circling a much larger counterpart at nearly a tenth of the speed of light, they hypothesized. At that speed, the smaller black hole would appear to brighten as it approached Earth’s line of sight under the relativistic Doppler beaming effect.

If correct, they predicted they would find a five-year cycle in the quasar’s ultraviolet emissions. Analyzing UV observations collected by NASA’s Hubble and GALEX space telescopes they found exactly that.

Abstract of Relativistic boost as the cause of periodicity in a massive black-hole binary candidate

Because most large galaxies contain a central black hole, and galaxies often merge, black-hole binaries are expected to be common in galactic nuclei. Although they cannot be imaged, periodicities in the light curves of quasars have been interpreted as evidence for binaries, most recently in PG 1302-102, which has a short rest-frame optical period of four years. If the orbital period of the black-hole binary matches this value, then for the range of estimated black-hole masses, the components would be separated by 0.007–0.017 parsecs, implying relativistic orbital speeds. There has been much debate over whether black-hole orbits could be smaller than one parsec. Here we report that the amplitude and the sinusoid-like shape of the variability of the light curve of PG 1302-102 can be fitted by relativistic Doppler boosting of emission from a compact, steadily accreting, unequal-mass binary. We predict that brightness variations in the ultraviolet light curve track those in the optical, but with a two to three times larger amplitude. This prediction is relatively insensitive to the details of the emission process, and is consistent with archival ultraviolet data. Follow-up ultraviolet and optical observations in the next few years can further test this prediction and confirm the existence of a binary black hole in the relativistic regime.

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3D-printed silicone guide with chemical cues helps regenerate complex nerves after injury

3-D scans of a nerve from different angles are used to create a custom regeneration guide for complex nerves (credit: University of Minnesota)

A national team of researchers used a combination of 3-D imaging and 3-D printing techniques to create a custom silicone guide implanted with biochemical cues to help nerve regeneration after an injury.

Nerve regeneration is a complex process, which is why regrowth of nerves after injury or disease is very rare and often permanent, according to the Mayo Clinic.

As a test, the researchers used a 3-D scanner to reverse-engineer the structure of a rat’s sciatic nerve. They then used a specialized, custom-built 3-D printer to print a regeneration guide containing 3D-printed chemical cues to promote both motor and sensory nerve regeneration within the same structure. The guide was then implanted into the rat by surgically grafting it to the cut ends of the nerve. Within about 10 to 12 weeks, the rat’s ability to walk again was improved.

A 3D-printed complex nerve-regeneration pathway implanted in a rat helped to improve walking in 10 to 12 weeks after implantation (credit: University of Minnesota)

“Someday we hope that we could have a 3D scanner and printer right at the hospital to create custom nerve guides right on site to restore nerve function,” said University of Minnesota mechanical engineering professor Michael McAlpine, the study’s lead researcher.

Conventional nerve guidance channels are typically fabricated around cylindrical substrates, so the resulting guidance devices are limited to linear structures. This is is the first time a study has shown the creation of a custom guide for regrowth of a complex nerve like the Y-shaped sciatic nerve, which has both sensory and motor branches.

“The exciting next step would be to implant these guides in humans rather than rats,” McAlpine said. For cases where a patient’s nerve is unavailable for scanning, McAlpine said there could someday be a “library” of scanned nerves from other people or cadavers that hospitals could use to create closely matched 3D-printed guides for patients.

The study by researchers from the University of Minnesota, Virginia Tech, University of Maryland, Princeton University, and Johns Hopkins University was published Thursday (Sept. 17) in the journal Advanced Functional Materials.


UMN College of Science and Engineering | 3D printing of a nerve regeneration guide [no audio]

Abstract of 3D Printed Anatomical Nerve Regeneration Pathways

A 3D printing methodology for the design, optimization, and fabrication of a custom nerve repair technology for the regeneration of complex peripheral nerve injuries containing bifurcating sensory and motor nerve pathways is introduced. The custom scaffolds are deterministically fabricated via a microextrusion printing principle using 3D models, which are reverse engineered from patient anatomies by 3D scanning. The bifurcating pathways are augmented with 3D printed biomimetic physical cues (microgrooves) and path-specific biochemical cues (spatially controlled multicomponent gradients). In vitro studies reveal that 3D printed physical and biochemical cues provide axonal guidance and chemotractant/chemokinetic functionality. In vivo studies examining the regeneration of bifurcated injuries across a 10 mm complex nerve gap in rats showed that the 3D printed scaffolds achieved successful regeneration of complex nerve injuries, resulting in enhanced functional return of the regenerated nerve. This approach suggests the potential of 3D printing toward advancing tissue regeneration in terms of: (1) the customization of scaffold geometries to match inherent tissue anatomies; (2) the integration of biomanufacturing approaches with computational modeling for design, analysis, and optimization; and (3) the enhancement of device properties with spatially controlled physical and biochemical functionalities, all enabled by the same 3D printing process.

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First application to pursue genome editing research in human embryos

Human embryos are at the center of a debate over the ethics of gene editing (credit: Dr. Yorgos Nikas/SPL)

The first application to pursue CRISPR/Cas9 genome-editing research in viable human embryos has been submitted to the UK’s fertility regulator by a team of researchers affiliated with the Francis Crick Institute in London.

“This research proposal is a troubling and provocative move,” commented Marcy Darnovsky, PhD, Executive Director of the Center for Genetics and Society.

“Modifying the genes of human embryos is deeply controversial because it can be used for worthwhile research on the one hand, or to produce genetically modified human beings on the other. A global public conversation about preventing such misuses is just getting underway, and this proposal could short-circuit those deliberations.

“It’s illegal in the UK and dozens of other countries to use a modified embryo to initiate a pregnancy, but in others — notably the U.S. — we don’t have that legal protection,” Darnovsky added. “If scientists and the regulatory agency in the UK are serious about responsible use of powerful new gene altering technologies, they won’t be rushing ahead in ways that could open the door to a world of genetically modified humans.”

If the UK Human Fertilisation & Embryology Authority were to issue this license, this would be the first approval of genome editing research on the human germline by a national regulatory body.

The resulting experiments would be the second of their kind in this highly controversial area of research. In April, scientists working out of China published research that they had created the first genetically modified human embryos—these embryos were nonviable, and the results of the CRISPR/Cas9 engineering were highly unsuccessful: producing off target mutations and mosaicism that underlined the limitations of our current understandings of genetics and genomics.

The response from the scientific community and the public after the first human embryo gene editing experiment in April was swift. Many scientists voiced support for either a pause or a moratorium on human germline modification.

On September 14, the National Academies announced that the International Summit on Human Gene Editing scheduled for December will now be co-hosted by the Royal Society (UK) and the Chinese Academy of Sciences.

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Minority Report, Limitless TV shows launch Monday, Tuesday

A sequel to Steven Spielberg’s epic movie, MINORITY REPORT is set in Washington, D.C., 10 years after the demise of Precrime, a law enforcement agency tasked with identifying and eliminating criminals … before their crimes were committed. Now, in 2065, crime-solving is different, and justice leans more on sophisticated and trusted technology than on the instincts of the precogs. Sept. 21 series premiere Mondays 9/8:00c

LIMITLESS, based on the feature film, is a fast-paced drama about Brian Finch, who discovers the brain-boosting power of the mysterious drug NZT and is coerced by the FBI into using his extraordinary cognitive abilities to solve complex cases for them. Sept. 22 series premiere Tuesdays 10/9c

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A new process for studying proteins associated with diseases

Schematic of phosphoprotein biosynthesis from E. coli bacteria. Sep-OTS: genetically encoded phosphoserine; CFPS: cell-free protein synthesis; NTPs: nucleoside triphosphates; lysis:  breaking down cell membrane. (credit: Javin P. Oza et al./Nature Communications)

Researchers from Northwestern University and Yale University have developed a new technology to help scientists understand how proteins work and fix them when they are broken. Such knowledge could pave the way for new drugs for a myriad of diseases, including cancer.

The human body turns its proteins on and off (to alter their function and activity in cells) using “phosphorylation” — the reversible attachment of phosphate groups to proteins. These “decorations” on proteins provide an enormous variety of functions and are essential to all forms of life. Little is known, however, about how this important dynamic process works in humans.

Phosphorylation: a hallmark of disease

Using a special strain of E. coli bacteria, the researchers built a cell-free protein synthesis platform technology that can manufacture large quantities of these human phosphoproteins for scientific study. The goal is to enable scientists to learn more about the function and structure of phosphoproteins and identify which ones are involved in disease.

The study was published Sept. 9 in an open-access paper by the journal Nature Communications.

Trouble in the phosphorylation process can be a hallmark of disease, such as cancer, inflammation and Alzheimer’s disease. The human proteome (the entire set of expressed proteins) is estimated to be phosphorylated at more than 100,000 unique sites, making study of phosphorylated proteins and their role in disease a daunting task.

“Our technology begins to make this a tractable problem,”  said  Michael C. Jewett, an associate professor of chemical and biological engineering who led the Northwestern team. “We now can make these special proteins at unprecedented yields, with a freedom of design that is not possible in living organisms. The consequence of this innovative strategy is enormous.”

A “plug-and-play” protein expression platform

Jewett and his colleagues combined state-of-the-art genome engineering tools and engineered biological “parts” into a “plug-and-play” protein expression platform that is cell-free. Cell-free systems activate complex biological systems without using living intact cells. Crude cell lysates, or extracts, are employed instead.

The researchers prepared cell lysates of genomically recoded bacteria that incorporate amino acids not found in nature. This allowed them to harness the cell’s engineered machinery and turn it into a factory, capable of on-demand biomanufacturing new classes of proteins.

To demonstrate their cell-free platform technology, the researchers produced a human kinase that is involved in tumor cell proliferation and showed that it was functional and active. Kinase is an enzyme (a protein acting as a catalyst) that transfers a phosphate group onto a protein. Through this process, kinases activate the function of proteins within the cell. Kinases are implicated in many diseases and, therefore, of particular interest.

“The ability to produce kinases for study should be useful in learning how these proteins function and in developing new types of drugs,” Jewett said.

Abstract of Robust production of recombinant phosphoproteins using cell-free protein synthesis

Understanding the functional and structural consequences of site-specific protein phosphorylation has remained limited by our inability to produce phosphoproteins at high yields. Here we address this limitation by developing a cell-free protein synthesis (CFPS) platform that employs crude extracts from a genomically recoded strain of Escherichia coli for site-specific, co-translational incorporation of phosphoserine into proteins. We apply this system to the robust production of up to milligram quantities of human MEK1 kinase. Then, we recapitulate a physiological signalling cascade in vitro to evaluate the contributions of site-specific phosphorylation of mono- and doubly phosphorylated forms on MEK1 activity. We discover that only one phosphorylation event is necessary and sufficient for MEK1 activity. Our work sets the stage for using CFPS as a rapid high-throughput technology platform for direct expression of programmable phosphoproteins containing multiple phosphorylated residues. This work will facilitate study of phosphorylation-dependent structure–function relationships, kinase signalling networks and kinase inhibitor drugs.

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A simulated quantum learning lab in Vienna that you can access virtually

Interference of complex molecules are pictured in the Kapitza-Dirac-Talbot-Lau interferometer (credit: Quantum Nanophysics group, University of Vienna; Image: Mathias Tomandl & Patrick Braun)

Ever feel like digging into quantum physics — and actually understanding it? Then you may enjoy a novel virtual hands-on remote learning environment developed by quantum physicists at the University of Vienna in collaboration with university and high-school students, and available free online.

The new teaching concept, called “Simulated Interactive Research Experiments” (SiReX), is described in an open-access paper in the journal Scientific Reports.

Simulation of the University of Vienna interferometer: measuring the two-dimensional interference pattern of molecules (credit: Mathias Tomandl et al./Scientific Reports)

The physicists, led by Markus Arndt at the University of Vienna, created two research laboratories as photorealistic computer simulations, allowing you to access simulated instruments in virtual experiments*.

The physicists say the virtual laboratories provide insights into fundamental understanding and applications of quantum mechanics with macromolecules and nanoparticles, including a wave-particle dualism experiment and  interferometry with large molecules.

A version of the virtual lab can also be experienced as an interactive exhibit in the Natural History Museum Vienna.

* Tip: skip the “find the coffee cups” practice task at the beginning.


Quantum Nanophysics group, University of Vienna| Interactive quantum lab

Abstract of Simulated Interactive Research Experiments as Educational Tools for Advanced Science

Experimental research has become complex and thus a challenge to science education. Only very few students can typically be trained on advanced scientific equipment. It is therefore important to find new tools that allow all students to acquire laboratory skills individually and independent of where they are located. In a design-based research process we have investigated the feasibility of using a virtual laboratory as a photo-realistic and scientifically valid representation of advanced scientific infrastructure to teach modern experimental science, here, molecular quantum optics. We found a concept based on three educational principles that allows undergraduate students to become acquainted with procedures and concepts of a modern research field. We find a significant increase in student understanding using our Simulated Interactive Research Experiment (SiReX), by evaluating the learning outcomes with semi-structured interviews in a pre/post design. This suggests that this concept of an educational tool can be generalized to disseminate findings in other fields.