A team of scientists from Columbia University, Arizona State University, the University of Michigan, and the California Institute of Technology (Caltech) have programmed an autonomous molecular “robot” made out of DNA to start, move, turn, and stop while following a DNA track.

The development could ultimately lead to molecular systems that might one day be used for medical therapeutic devices and molecular-scale reconfigurable robots—robots made of many simple units that can reposition or even rebuild themselves to accomplish different tasks.

A paper describing the work appears in the current issue of the journal Nature.

The traditional view of a robot is that it is “a machine that senses its environment, makes a decision, and then does something—it acts,” says Erik Winfree, associate professor of computer science, computation and neural systems, and bioengineering at Caltech.

Milan N. Stojanovic, a faculty member in the Division of Experimental Therapeutics at Columbia University, led the project and teamed up with Winfree and Hao Yan, professor of chemistry and biochemistry at Arizona State University and an expert in DNA nanotechnology, and with Nils G. Walter, professor of chemistry and director of the Single Molecule Analysis in Real-Time (SMART) Center at the University of Michigan in Ann Arbor, for what became a modern-day self-assembly of like-minded scientists with the complementary areas of expertise needed to tackle a tough problem.

Shrinking robots down to the molecular scale would provide, for molecular processes, the same kinds of benefits that classical robotics and automation provide at the macroscopic scale. Molecular robots, in theory, could be programmed to sense their environment (say, the presence of disease markers on a cell), make a decision (that the cell is cancerous and needs to be neutralized), and act on that decision (deliver a cargo of cancer-killing drugs).

Or, like the robots in a modern-day factory, they could be programmed to assemble complex molecular products. The power of robotics lies in the fact that once programmed, the robots can carry out their tasks autonomously, without further human intervention.

With that promise, however, comes a practical problem: how do you program a molecule to perform complex behaviors?

“In normal robotics, the robot itself contains the knowledge about the commands, but with individual molecules, you can’t store that amount of information, so the idea instead is to store information on the commands on the outside,” says Walter. And you do that, says Stojanovic, “by imbuing the molecule’s environment with informational cues.”

“We were able to create such a programmed or ‘prescribed’ environment using DNA origami,” explains Yan. DNA origami, an invention by Caltech Senior Research Associate Paul W. K. Rothemund, is a type of self-assembled structure made from DNA that can be programmed to form nearly limitless shapes and patterns (such as smiley faces or maps of the Western Hemisphere or even electrical diagrams). Exploiting the sequence-recognition properties of DNA base pairing, DNA origami are created from a long single strand of DNA and a mixture of different short synthetic DNA strands that bind to and “staple” the long DNA into the desired shape. The origami used in the Nature study was a rectangle that was 2 nanometers (nm) thick and roughly 100 nm on each side.

The researchers constructed a trail of molecular “bread crumbs” on the DNA origami track by stringing additional single-stranded DNA molecules, or oligonucleotides, off the ends of the staples. These represent the cues that tell the molecular robots what to do—start, walk, turn left, turn right, or stop, for example—akin to the commands given to traditional robots.

The molecular robot the researchers chose to use—dubbed a “spider”—was invented by Stojanovic several years ago, at which time it was shown to be capable of extended, but undirected, random walks on two-dimensional surfaces, eating through a field of bread crumbs.

To build the 4-nm-diameter molecular robot, the researchers started with a common protein called streptavidin, which has four symmetrically placed binding pockets for a chemical moiety called biotin. Each robot leg is a short biotin-labeled strand of DNA, “so this way we can bind up to four legs to the body of our robot,” Walter says. “It’s a four-legged spider,” quips Stojanovic. Three of the legs are made of enzymatic DNA, which is DNA that binds to and cuts a particular sequence of DNA. The spider also is outfitted with a “start strand”—the fourth leg—that tethers the spider to the start site (one particular oligonucleotide on the DNA origami track). “After the robot is released from its start site by a trigger strand, it follows the track by binding to and then cutting the DNA strands extending off of the staple strands on the molecular track,” Stojanovic explains.

“Once it cleaves,” adds Yan, “the product will dissociate, and the leg will start searching for the next substrate.” In this way, the spider is guided down the path laid out by the researchers. Finally, explains Yan, “the robot stops when it encounters a patch of DNA that it can bind to but that it cannot cut,” which acts as a sort of flypaper.

Although other DNA walkers have been developed before, they’ve never ventured farther than about three steps. “This one,” says Yan, “can walk up to about 100 nanometers. That’s roughly 50 steps.”

“This in itself wasn’t a surprise,” adds Winfree, “since Milan’s original work suggested that spiders can take hundreds if not thousands of processive steps. What’s exciting here is that not only can we directly confirm the spiders’ multistep movement, but we can direct the spiders to follow a specific path, and they do it all by themselves—autonomously.”

In fact, using atomic force microscopy and single-molecule fluorescence microscopy, the researchers were able to watch directly spiders crawling over the origami, showing that they were able to guide their molecular robots to follow four different paths.

“Monitoring this at a single molecule level is very challenging,” says Walter. “This is why we have an interdisciplinary, multi-institute operation. We have people constructing the spider, characterizing the basic spider. We have the capability to assemble the track, and analyze the system with single-molecule imaging. That’s the technical challenge.” The scientific challenges for the future, Yan says, “are how to make the spider walk faster and how to make it more programmable, so it can follow many commands on the track and make more decisions, implementing logical behavior.”

“In the current system,” says Stojanovic, “interactions are restricted to the walker and the environment. Our next step is to add a second walker, so the walkers can communicate with each other directly and via the environment. The spiders will work together to accomplish a goal.” Adds Winfree, “The key is how to learn to program higher-level behaviors through lower-level interactions.”

Such collaboration ultimately could be the basis for developing molecular-scale reconfigurable robots—complicated machines that are made of many simple units that can reorganize themselves into any shape—to accomplish different tasks, or fix themselves if they break. For example, it may be possible to use the robots for medical applications. “The idea is to have molecular robots build a structure or repair damaged tissues,” says Stojanovic.

“You could imagine the spider carrying a drug and bonding to a two-dimensional surface like a cell membrane, finding the receptors and, depending on the local environment,” adds Yan, “triggering the activation of this drug.”

Such applications, while intriguing, are decades or more away. “This may be 100 years in the future,” Stojanovic says. “We’re so far from that right now.”

“But,” Walter adds, “just as researchers self-assemble today to solve a tough problem, molecular nanorobots may do so in the future.”

The other coauthors on the paper, “Molecular robots guided by prescriptive landscapes,” are Kyle Lund and Jeanette Nangreave from Arizona State University; Anthony J. Manzo, Alexander Johnson-Buck, and Nicole Michelotti from the University of Michigan; Nadine Dabby from Caltech; and Steven Taylor and Renjun Pei from Columbia University. The work was supported by the National Science Foundation, the Army Research Office, the Office of Naval Research, the National Institutes of Health, the Department of Energy, the Searle Foundation, the Lymphoma and Leukemia Society, the Juvenile Diabetes Research Foundation, and a Sloan Research Fellowship.

Contact: Kathy Svitil ksvitil@caltech.edu

Image Credit: Courtesy of Paul Michelotti

The future of clean green solar power may well hinge on scientists being able to unravel the mysteries of photosynthesis, the process by which green plants convert sunlight into electrochemical energy. To this end, researchers with the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC), Berkeley have recorded the first observation and characterization of a critical physical phenomenon behind photosynthesis known as quantum entanglement.

Previous experiments led by Graham Fleming, a physical chemist holding joint appointments with Berkeley Lab and UC Berkeley, pointed to quantum mechanical effects as the key to the ability of green plants, through photosynthesis, to almost instantaneously transfer solar energy from molecules in light harvesting complexes to molecules in electrochemical reaction centers. Now a new collaborative team that includes Fleming have identified entanglement as a natural feature of these quantum effects. When two quantum-sized particles, for example a pair of electrons, are “entangled,” any change to one will be instantly reflected in the other, no matter how far apart they might be. Though physically separated, the two particles act as a single entity.

“This is the first study to show that entanglement, perhaps the most distinctive property of quantum mechanical systems, is present across an entire light harvesting complex,” says Mohan Sarovar, a post-doctoral researcher under UC Berkeley chemistry professor Birgitta Whaley at the Berkeley Center for Quantum Information and Computation. “While there have been prior investigations of entanglement in toy systems that were motivated by biology, this is the first instance in which entanglement has been examined and quantified in a real biological system.”

The results of this study hold implications not only for the development of artificial photosynthesis systems as a renewable non-polluting source of electrical energy, but also for the future development of quantum-based technologies in areas such as computing – a quantum computer could perform certain operations thousands of times faster than any conventional computer.

“The lessons we’re learning about the quantum aspects of light harvesting in natural systems can be applied to the design of artificial photosynthetic systems that are even better,” Sarovar says. “The organic structures in light harvesting complexes and their synthetic mimics could also serve as useful components of quantum computers or other quantum-enhanced devices, such as wires for the transfer of information.”

The schematic on the left shows the absorption of light by a light harvesting complex and the transport of the resulting excitation energy to the reaction center through the FMO protein. On the right is a monomer of the FMO protein, showing its orientation relative to the antenna and the reaction center. The numbers label FMO’s seven pigment molecules. (Image from Mohan Sarovar)

What may prove to be this study’s most significant revelation is that contrary to the popular scientific notion that entanglement is a fragile and exotic property, difficult to engineer and maintain, the Berkeley researchers have demonstrated that entanglement can exist and persist in the chaotic chemical complexity of a biological system.

“We present strong evidence for quantum entanglement in noisy non-equilibrium systems at high temperatures by determining the timescales and temperatures for which entanglement is observable in a protein structure that is central to photosynthesis in certain bacteria,” Sarovar says.

Sarovar is a co-author with Fleming and Whaley of a paper describing this research that appears on-line in the journal Nature Physics titled “Quantum entanglement in photosynthetic light-harvesting complexes.” Also co-authoring this paper was Akihito Ishizaki in Fleming’s research group.

Green plants and certain bacteria are able to transfer the energy harvested from sunlight through a network of light harvesting pigment-protein complexes and into reaction centers with nearly 100-percent efficiency. Speed is the key – the transfer of the solar energy takes place so fast that little energy is wasted as heat. In 2007, Fleming and his research group reported the first direct evidence that this essentially instantaneous energy transfer was made possible by a remarkably long-lived, wavelike electronic quantum coherence.

Using electronic spectroscopy measurements made on a femtosecond (millionths of a billionth of a second) time-scale, Fleming and his group discovered the existence of “quantum beating” signals, coherent electronic oscillations in both donor and acceptor molecules. These oscillations are generated by the excitation energy from captured solar photons, like the waves formed when stones are tossed into a pond. The wavelike quality of the oscillations enables them to simultaneously sample all the potential energy transfer pathways in the photosynthetic system and choose the most efficient. Subsequent studies by Fleming and his group identified a closely packed pigment-protein complex in the light harvesting portion of the photosynthetic system as the source of coherent oscillations.

“Our results suggested that correlated protein environments surrounding pigment molecules (such as chlorophyll) preserve quantum coherence in photosynthetic complexes, allowing the excitation energy to move coherently in space, which in turn enables highly efficient energy harvesting and trapping in photosynthesis,” Fleming says.

In this new study, a reliable model of light harvesting dynamics developed by Ishizaki and Fleming was combined with the quantum information research of Whaley and Sarovar to show that quantum entanglement emerges as the quantum coherence in photosynthesis systems evolves. The focus of their study was the Fenna-Matthews-Olson (FMO) photosynthetic light-harvesting protein, a molecular complex found in green sulfur bacteria that is considered a model system for studying photosynthetic energy transfer because it consists of only seven pigment molecules whose chemistry has been well characterized.

“We found numerical evidence for the existence of entanglement in the FMO complex that persisted over picosecond timescales, essentially until the excitation energy was trapped by the reaction center,” Sarovar says.

“This is remarkable in a biological or disordered system at physiological temperatures, and illustrates that non-equilibrium multipartite entanglement can exist for relatively long times, even in highly decoherent environments.”

The research team also found that entanglement persisted across distances of about 30 angstroms (one angstrom is the diameter of a hydrogen atom), but this length-scale was viewed as a product of the relatively small size of the FMO complex, rather than a limitation of the effect itself.

“We expect that long-lived, non-equilibrium entanglement will also be present in larger light harvesting antenna complexes, such as LH1 and LH2, and that in such larger light harvesting complexes it may also be possible to create and support multiple excitations in order to access a richer variety of entangled states,” says Sarovar.

The research team was surprised to see that significant entanglement persisted between molecules in the light harvesting complex that were not strongly coupled (connected) through their electronic and vibrational states. They were also surprised to see how little impact temperature had on the degree of entanglement.

“In the field of quantum information, temperature is usually considered very deleterious to quantum properties such as entanglement,” Sarovar says. “But in systems such as light harvesting complexes, we see that entanglement can be relatively immune to the effects of increased temperature.”

This research was supported in part by U.S. Department of Energy’s Office of Science, and in part by a grant from the Defense Advanced Research Projects Agency (DARPA).

Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California. Visit our website at http://www.lbl.gov.

If life has evolved on Sat­urn’s frig­id moon, Ti­tan, it would be strange, smelly—and po­tent­ial­ly ex­plo­sive, new re­search sug­gests.

The con­clu­sions come from as­tro­bi­ol­o­gist Wil­liam Bains, who pre­s­ents his re­search at the Na­tional As­tron­o­my Meet­ing in Glas­gow, Scot­land on April 13.

“Hol­ly­wood would have prob­lems with these al­iens,” said Bains. “Beam one on­to the Star­ship En­ter­prise and it would boil and then burst in­to flames, and the fumes would kill eve­ry­one in range. Even a ti­ny whiff of its breath would smell un­be­lievably hor­ri­ble.

“But I think it is all the more in­ter­est­ing for that rea­son. Would­n’t it be sad if the most al­ien things we found in the gal­axy were just like us, but blue and with tail­s?” added Bains, re­fer­ring to the tall ex­tra­ter­res­tri­als from the mov­ie Av­a­tar.

Bains, whose re­search is car­ried out through Ru­fus Sci­en­tif­ic Ltd. in Cam­bridge, U.K. and the Mas­sachusetts In­sti­tute of Tech­nol­o­gy, is stu­dy­ing just how ex­treme life’s chem­is­try can be.

Life on Ti­tan, Sat­urn’s larg­est moon, is one of strang­er sce­nar­i­os un­der ex­amina­t­ion. Ti­tan is twice as large as our Moon and has a thick at­mos­phere of freez­ing, or­ange smog. At ten times our dis­tance from the Sun, it is a frig­id place, with a sur­face tem­per­a­ture of mi­nus 180 de­grees Cel­si­us (mi­nus 292 Fah­ren­heit). All the wa­ter is ice; the only liq­uids are meth­ane and eth­ane, fill­ing what sci­en­tists be­lieve are ponds and lakes.

“So, if life were to ex­ist on Ti­tan, it must have blood based on liq­uid meth­ane, not wa­ter. That means its whole chem­is­try is radic­ally dif­fer­ent. The mo­le­cules must be made of a wid­er va­ri­e­ty of el­e­ments than we use, but put to­geth­er in smaller molecules. It would al­so be much more chem­ic­ally re­ac­tive,” said Bains.

This blood would have to con­tain dis­solved chem­icals, but few chem­icals dis­solve easily in liq­uid meth­ane. Most mo­le­cules can’t dis­solve in it if they have more than six atoms not count­ing eas­ily-dis­solved hy­dro­gen. So a me­tab­o­lism run­ning in liq­uid meth­ane will have to be built of smaller mo­le­cules than in Earth bio­chem­is­try, which is typ­ic­ally built of mod­ules of around 10 atoms apart from hy­dro­gen.

You can only build around 3,400 dif­fer­ent mo­le­cules with­in the above-described lim­ita­t­ions on Ti­tan, Bains said. In con­trast, he added, one can build around 10 mil­lion or more dif­fer­ent mo­le­cules fit­ting Earth’s re­quired spe­cif­ica­t­ions, al­though only about 700 are ac­tu­ally used.

“The is­sue is not how many mo­le­cules you can make, but wheth­er you can make the col­lec­tion you need to as­sem­ble a me­tab­o­lism. It is like try­ing to find bits of wood in a lumber-yard to make a ta­ble. In the­o­ry you only need five. But you may have a lumber-yard full of off­cuts and still not find ex­actly the right five… so you need the po­ten­tial to make many more mo­le­cules than you ac­tu­ally need. Thus the six-atom chem­icals on Ti­tan would have to in­clude much more di­verse bond types [link­ing the atoms] and probably more di­verse el­e­ments, in­clud­ing sul­phur and phos­pho­rus.”

The el­e­ments would have to ap­pear in much more di­verse forms, as well as in forms that would be highly un­sta­ble on the Earth en­vi­ron­ment—hence the ex­plo­siveness, he added.

En­er­gy is anoth­er fac­tor that would af­fect the type of life that could evolve on Ti­tan. With sun­light a tenth of a per­cent as in­tense on Ti­tan’s sur­face as on the sur­face of Earth, en­er­gy is probably in short sup­ply. “Rapid move­ment or growth needs a lot of en­er­gy, so slow-growing, lichen-like or­gan­isms are pos­si­ble in the­o­ry, but ve­loci­rap­tors are pret­ty much ruled out,” said Bains.

Image Credit: © 2008 Karl Ko­foed

In a world first an international team of researchers have successfully extracted ancient DNA from the eggshells of various species of extinct birds.

The research, published in scientific journal Proceedings of the Royal Society B, shows that fossil eggshell is a previously unrecognised source of ancient DNA and can provide exceptional long-term preservation of DNA in warmer climates. The findings will boost research in archaeology and biology where species identifications can add significantly to our understanding of biodiversity, evolutionary processes, past environmental change and dispersal of animal and human populations.

The study includes samples of Aepyornis sp, the giant Madagascan elephant bird collected by Dr Jean-Luc Schwenninger, a Quaternary geochronologist based at the Research Laboratory for Archaeology and the History of Art (RLAHA) at Oxford University. The bird looked like an outsized ostrich, standing about three metres high and weighing in excess of half a tonne. It was the heaviest bird to have ever existed and produced eggs with a capacity of 11L (equivalent to over two hundred chicken eggs or seven ostrich eggs). Its eggs are the largest eggs ever known.

Since 1991, Schwenninger and a team from Sheffield University, the University of Colorado, and Antananarivo’s National Museum of Art and Archaeology in Madagascar have conducted large scale archaeological surveys of the Southern region of Madagascar and studied the timing of extinction of these giant flightless birds. Whilst scouring the coastal dunes of Southern Madagascar they have found evidence of many of the bird’s former nesting sites from concentrations of eggshell debris. They have also excavated archaeological sites which document the rise and fall of a lost civilization with long-distance trade contacts to Africa’s Swahili coast, the Persian Gulf and China.

Dr Schwenninger and his colleague Professor Michael Parker Pearson, from the University of Sheffield, believe that by the time this civilization flourished, from the 11th to the 13th century, the population of elephant birds was in serious decline. The precise cause of extinction is not yet fully understood but it is probably linked to the arrival of humans.

AMS radiocarbon dating of eggshell remains, carried out at the Oxford Radiocarbon Accelerator Unit based at RLAHA, indicate that most of the birds seem to have died out at about the same time as large numbers of settlements appear in the archaeological record at around AD 1000. The French governor Etienne de Flacourt refers to indigenous sightings of the Aepyornis in 1650 which describe the bird as a ‘type of ostrich which people cannot catch and which searches out the most deserted places’.

The DNA breakthrough was achieved when Dr Schwenninger and doctoral student James Haile, based at Oxford’s Ancient Biomolecules Centre considered analysing samples of sediment for his research. Dr Shwenninger said: ‘This time last year, I gave James a few samples from several of our archaeological and subfossil sites in Madagascar to see if any plant or animal DNA could be extracted. I also mentioned to him that I had some eggshell which might be worth looking at. In fact, we had already tried this back in 1998 and again in 2003 but without success. He was very keen to give it another go and he succeeded where others, including his thesis supervisor had previously failed.’

Two teams of Oxford University researchers led by Professors Judith Armitage and David Stuart have made the first steps towards being able to engineer a bacterial cell that can sense and respond to novel environmental cues. The groups demonstrated that it should be possible to design synthetic signalling circuits inside a cell, ultimately enabling the development of new biosensors.

The ability of bacteria to respond to environmental cues is a universal feature of living cells. Evolution has created a vast array of signalling mechanisms that enable cells to react in many ways to changes in their surroundings. One of the most important of these is a two-component signalling circuit which is widely used by bacteria. It comprises a protein kinase, which acts as the sensor, and its partner protein known as a response regulator. Some species of bacteria have over 150 different sensor-response regulator pairs in a single cell, so the specificity between these pairs has to be tightly controlled to prevent ‘crossed wires’ between signalling pathways.

The two Oxford groups combined their expertise in structural biology and biochemistry to address where this specificity comes from. They used extremely bright pinpoints of light produced by the UK’s national synchrotron facility, Diamond Light Source in south Oxfordshire, to carry out X-ray crystallography, a method that allows visualization of proteins at an atomic level. Using this approach, the researchers solved the three-dimensional structure of one of these two-component complexes found in the bacterium Rhodobacter sphaeroides. This complex is crucial for a process known as chemotaxis which controls the movement of a bacterium when it senses a chemical or nutrient gradient in its environment. Based on the crystallography results, the researchers were able to pinpoint the specific amino acids that are required for this molecular recognition. They found that one amino acid on the response regulator pointed out like a finger towards a pocket on the sensor, enabling the two proteins to fit snugly together. By introducing this finger into other response regulator proteins, which do not normally partner this specific sensor, they were able to change their specificity and re-engineer the chemotaxis pathway.

This is the first time that researchers have re-designed the intracellular part of the chemotaxis circuitry. This re-engineering paves the way for producing custom-designed circuits for applications in systems biology.

“This is a significant step on the road to identifying the critical amino acid interface that allows discrimination between apparently related proteins and their partners, and a step along the road to rational design of protein signalling networks.”
Professor Judith Armitage, Department of Biochemistry

“The aim is to understand the system so well that you’re able to change it in any way you like”, says Christian Bell, the postgraduate student who worked on the project in both labs. “The dream will be a synthetic cell that does exactly what you want.”

The robust, efficient shell of a tiny deep-sea snail could pro­vide in­spira­t­ion for ad­vanc­es in hu­man body ar­mor de­sign, re­search­ers say.

Ma­te­ri­als sci­ent­ist Chris­tine Or­tiz of the Mas­sa­chu­setts In­sti­tute of Tech­nol­o­gy and col­leagues in­ves­t­i­gated the iron-rich shell of the snail Cryso­ma­l­lon squa­m­ife­rum, re­cently dis­cov­ered near deep-sea vents in the In­di­an Ocean.

The shell has an un­usu­al three-lay­ered de­sign and is un­ique among an­i­mal ar­mor for in­clud­ing a lay­er based on iron sul­fide, chem­i­cal com­pounds of iron and sul­fur, re­search­ers said.

They stud­ied the me­chan­i­cal prop­er­ties of the in­di­vid­ual lay­ers in cross-sections of the shell at the mo­lec­u­lar lev­el and used the da­ta to de­vel­op a com­put­er mod­el of the snail’s out­er skel­e­ton.

Sim­ula­t­ions of an­i­mals’ nat­u­ral pro­tec­tive sys­tems can al­low re­search­ers and en­gi­neers to ex­plore how an­i­mals de­fend them­selves while re­tain­ing free move­ment and body regula­t­ion, the sci­ent­ists not­ed. They ex­am­ined how the shell pro­tects the snail against a pred­a­tor at­tack and found that each of the shel­l’s three lay­ers seems to be re­spon­si­ble for dif­fer­ent as­pects of the ar­mor’s ef­fec­tive­ness.

The mid­dle lay­er is a “com­pli­ant” lay­er sand­wiched be­tween two stiffer “min­er­al­ized” lay­ers, they found. The in­ner, cal­cium-rich lay­er pro­vides struct­ural sup­port, while the more flex­ible mid­dle layer helps pre­vent cracks in other lay­ers from spread­ing. The outer lay­er prov­ides add­i­tional stiff­ness but also is sus­cep­tible to de­vel­op­ing “mi­cro­frac­tures” that pa­rad­ox­ic­ally head off more ser­ious cracks by dis­sip­a­ting en­ergy.

Ortiz’ at­ten­tion was drawn to the snail in 2003, when its discovery was first reported. The ani­mal lives in a harsh en­viron­ment on the sea floor, near vents that spew hot water. Thus it is exposed to fluc­tu­ations in temp­er­ature as well as high acidity, and also faces attack from pre­da­tors such as crabs and other snails.

When a crab attacks a snail, it grasps the shell and squeezes it until it breaks—for days if ne­ces­sary.

The three-layer ar­range­ment pro­tects against pen­etra­t­ion, im­proves en­er­gy dis­sipa­t­ion, and re­sists bend­ing, the in­vest­i­gators found. This could pro­vide a mod­el for de­vel­oping pro­tec­tive ma­te­ri­als for hu­mans, they noted. Their re­port ap­pears in this week’s early on­line is­sue of the re­search jour­nal Pro­ceed­ings of the Na­tio­n­al Aca­de­my of Sci­en­ces.

Sci­en­tists say they have man­aged to make plas­tics through “bio-en­gi­neer­ing” rath­er than through the use of fos­sil fu­els that con­trib­ute to glob­al warm­ing.

The find­ings are pub­lished in two pa­pers in the jour­nal Bi­o­tech­nol­ogy and Bi­o­en­gi­neer­ing to mark the jour­nal’s 50th an­ni­ver­sa­ry.

Poly­mers are mo­le­cules found in eve­ry­day life in the form of plas­tics and rub­bers. The re­search­ers, from Ko­rea Ad­vanced In­sti­tute of Sci­ence and Tech­nol­o­gy and Ko­re­an chem­i­cal com­pa­ny LG Chem, fo­cused their re­search on poly­lac­tic ac­id, a bi­o­log­ic­ally-based pol­y­mer.

“The polyesters and oth­er pol­y­mers we use eve­ry­day are mostly de­rived from fos­sil oils made through the re­fin­ery or chem­i­cal pro­cess,” said In­sti­tute re­searcher Sang Yup Lee. Poly­lac­tic ac­id “is con­sid­ered a good al­ter­na­tive to petroleum-based plas­tics as it is both bi­o­de­grad­able and has a low tox­icity to hu­mans.”

Un­til now the pol­y­mer had been pro­duced in a com­plex, costly two-step chem­i­cal pro­cess, he added. Lee’s team de­vel­oped a one-stage pro­cess in which en­gi­neered E. coli bac­te­ria pro­duced poly­lac­tic ac­id and as­so­ci­at­ed pol­y­mers through fer­menta­t­ion, a met­a­bol­ic pro­cess.

“This means that a de­vel­oped E. coli strain is now ca­pa­ble of ef­fi­ciently pro­duc­ing un­nat­u­ral pol­y­mers, through a one-step fer­menta­t­ion pro­cess,” he said.

“Global warm­ing and oth­er en­vi­ron­men­tal prob­lems are urg­ing us to de­vel­op sus­tain­a­ble pro­cesses based on re­new­able re­sources,” added Lee. “This new strat­e­gy should be gen­er­ally use­ful for de­vel­oping oth­er en­gi­neered or­gan­isms ca­pa­ble of pro­duc­ing var­i­ous un­nat­u­ral pol­y­mers by di­rect fer­menta­t­ion from re­new­able re­sources.”

An international group of scientists is proposing to generate whole genome sequences for 10,000 vertebrate species using technology so new it hasn’t yet been invented. But the scientists say new genome sequencing instruments that will allow them to embark on the project may be available within a year or two.

In preparation, they are identifying collaborators who can help assemble a collection of frozen or otherwise suitably preserved tissues or DNA samples from these species.

Their proposal, called “Genome 10K,” will be published this week in the Journal of Heredity.

“The idea behind the project is to prepare for this third generation of DNA sequencing technology that began with the Humane Genome Project,” said Oregon State University’s Scott Baker, who edits the Journal of Heredity. “Whereas that project took nearly 10 years at a cost of more than $3 billion, the goal now is to sequence an entire genome in less than a week, for a cost of less than $1,000.

“If that happens, the impact would be remarkable,” added Baker. “And it will happen – the only question is, how soon?”

Baker, who is associate director of OSU’s Marine Mammal Institute, is one of more than 50 scientists from around the world who is collaborating on the proposal. He is coordinating the effort to assemble DNA samples for all known species of cetaceans – whales, dolphins and porpoises – a task made more difficult because the exact number of species keeps changing.

As DNA analysis becomes more sophisticated, Baker said, molecular differences are emerging among some animals thought to belong to the same species.

“We are adding a new species every year or two,” Baker said, “and there is some disagreement about what criteria we should use to describe new species. But to date, more than 90 species have been identified and officially recognized that will require tissue or DNA samples.”

Thus far, Baker and his colleagues have viable DNA samples from 87 of those species, stored at OSU’s Hatfield Marine Science Center in Newport, Ore., at the University of Auckland in New Zealand, and at NOAA’s Southwest Fisheries Science Center in La Jolla, Calif., which holds the largest repository of cetacean tissues.

One of the challenges is to obtain samples for rare, endangered and even extinct species, Baker said.

“We have thousands of samples from humpback whales, for example,” he pointed out. “But there are a few cetacean species that are known literally from only a single skull, and it can be tough to extract DNA from that.”

The feasibility of sequencing 10,000 vertebrate genomes “requires only one more order of magnitude reduction in the cost of DNA sequencing, following the four orders of magnitude reduction we have seen in the last 10 years,” the scientists write in their article.

The variety of species identified will present different challenges for genome sequencing, Baker says, and whales, dolphins and porpoises could be among the most difficult.

“With some species of mammals, the computational assembly process is relatively simple – you start with one DNA sequence and stitch it together with an existing sequence that is similar, but not identical,” Baker said. “With whales, though, it is what’s called a ‘de-novo’ assembly. There is no template to follow.

“It’s like a gigantic jigsaw puzzle and you have to figure out where the pieces go,” he added.

Baker and his colleagues have been working for nearly 20 years on creating DNA barcodes for different cetacean species. The ability to create entire genome sequences would be of enormous benefits to conservation and basic scientific understanding of cetaceans, he said.

“It would give us tremendous new insight into a group of mammals that went through one of the most remarkable adaptations in evolutionary history,” Baker pointed out. “Cetaceans represent an incredible range of ‘extremophiles,’ including the blue whale, which can reach up to 100 feet in length, the bowhead whale, thought to live up to 200 years of age, and the sperm whales, capable of diving to more than a mile in depth.

“Yet despite this rapid adaptation in physiology and physical form, the molecular evolution of whales is 10 times slower than in other mammals,” Baked added. “This may help us find out why. The more we learn about how whales and dolphins have evolved – and how they are similar or different in genetic diversity – the better we will be able to protect species driven to the verge of extinction.”

The Genome 10K proposal is available free online at the Journal of Heredity, http://jhered.oxfordjournals.org

Further information is available from the Genome 10K Community of Scientists, http://www.genome10k.org

A ground-breaking census of 500 stars, 70 of which are known to host planets, has successfully linked the long-standing “lithium mystery” observed in the Sun to the presence of planetary systems. Using ESO’s successful HARPS spectrograph, a team of astronomers has found that Sun-like stars that host planets have destroyed their lithium much more efficiently than “planet-free” stars. This finding does not only shed light on the lack of lithium in our star, but also provides astronomers with a very efficient way of finding stars with planetary systems.

“For almost 10 years we have tried to find out what distinguishes stars with planetary systems from their barren cousins,” says Garik Israelian, lead author of a paper appearing this week in the journal Nature. “We have now found that the amount of lithium in Sun-like stars depends on whether or not they have planets.”

Low levels of this chemical element have been noticed for decades in the Sun, as compared to other solar-like stars, and astronomers have been unable to explain the anomaly. The discovery of a trend among planet-bearing stars provides a natural explanation to this long-standing mystery. “The explanation of this 60 year-long puzzle is for us rather simple,” adds Israelian. “The Sun lacks lithium because it has planets.”

This conclusion is based on the analysis of 500 stars, including 70 planet-hosting stars. Most of these stars were monitored for several years with ESO’s High Accuracy Radial Velocity Planet Searcher. This spectrograph, better known as HARPS, is attached to ESO’s 3.6-metre telescope and is the world’s foremost exoplanet hunter. “This is the best possible sample available to date to understand what makes planet-bearing stars unique,” says co-author Michel Mayor.

The astronomers looked in particular at Sun-like stars, almost a quarter of the whole sample. They found that the majority of stars hosting planets possess less than 1% of the amount of lithium shown by most of the other stars. “Like our Sun, these stars have been very efficient at destroying the lithium they inherited at birth,” says team member Nuno Santos. “Using our unique, large sample, we can also prove that the reason for this lithium reduction is not related to any other property of the star, such as its age.”

Unlike most other elements lighter than iron, the light nuclei of lithium, beryllium and boron are not produced in significant amounts in stars. Instead, it is thought that lithium, composed of just three protons and four neutrons, was mainly produced just after the Big Bang, 13.7 billion years ago. Most stars will thus have the same amount of lithium, unless this element has been destroyed inside the star.

This result also provides the astronomers with a new, cost-effective way to search for planetary systems: by checking the amount of lithium present in a star astronomers can decide which stars are worthy of further significant observing efforts.

Now that a link between the presence of planets and curiously low levels of lithium has been established, the physical mechanism behind it has to be investigated. “There are several ways in which a planet can disturb the internal motions of matter in its host star, thereby rearrange the distribution of the various chemical elements and possibly cause the destruction of lithium. It is now up to the theoreticians to figure out which one is the most likely to happen,” concludes Mayor.
More Information

This research was presented in a paper that appears in the 12 November 2009 issue of Nature (Enhanced lithium depletion in Sun-like stars with orbiting planets, by G. Israelian et al.).

The team is composed of Garik Israelian, Elisa Delgado Mena, Carolina Domínguez Cerdeña, and Rafael Rebolo (Instituto de Astrofisíca de Canarias, La Laguna, Tenerife, Spain), Nuno Santos and Sergio Sousa (Centro de Astrofisica, Universidade de Porto, Portugal), Michel Mayor and Stéphane Udry (Observatoire de Genève, Switzerland), and Sofia Randich (INAF, Osservatorio di Arcetri, Firenze, Italy).

ESO, the European Southern Observatory, is the foremost intergovernmental astronomy organisation in Europe and the world’s most productive astronomical observatory. It is supported by 14 countries: Austria, Belgium, the Czech Republic, Denmark, France, Finland, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, Switzerland and the United Kingdom. ESO carries out an ambitious programme focused on the design, construction and operation of powerful ground-based observing facilities enabling astronomers to make important scientific discoveries. ESO also plays a leading role in promoting and organising cooperation in astronomical research. ESO operates three unique world-class observing sites in Chile: La Silla, Paranal and Chajnantor. At Paranal, ESO operates the Very Large Telescope, the world’s most advanced visible-light astronomical observatory. ESO is the European partner of a revolutionary astronomical telescope ALMA, the largest astronomical project in existence. ESO is currently planning a 42-metre European Extremely Large optical/near-infrared Telescope, the E-ELT, which will become “the world’s biggest eye on the sky”.

Read on for more information:

Lasers can be used to gen­er­ate ex­treme states of mat­ter si­m­i­lar to those pro­duced near a black hole, re­ports a study pub­lished on­line this week in the re­search jour­nal Na­ture Phys­ics.

Black holes are ob­jects in space that are so com­pact, they pro­duce a fe­ro­cious gravita­t­ional field that cap­tures an­y­thing that strays too close, even light rays.

Albert Ein­stein cal­cu­lat­ed that black holes would al­so cre­ate se­vere dis­tor­tions of space and time in their vicin­ity. Black holes are fur­ther­more of­ten sur­rounded by vi­o­lent ac­ti­vity as stars, gas and dust are gob­bled up.

But con­di­tions around black holes have been hard to stu­dy, ex­cept from great dis­tances. The abil­ity to recre­ate these states in the lab­o­r­a­to­ry makes it much eas­er to study the pro­cesses that oc­cur near black holes and oth­er si­m­i­larly mas­sive as­t­ro­phys­i­cal ob­jects, as well as to bet­ter in­ter­pret the as­tronomical mea­sure­ments of these ob­jects, phys­i­cists say.

Near a black hole, hot gas­es be­come ion­ized, or elec­tric­ally charged, thanks to blasts of light from ob­jects that heat up as they are vi­o­lently sucked in­to the dense cen­tral mass.

These charged, hot gas­es, known as photoi­on­ized plas­mas, give off a char­ac­ter­is­tic spec­trum of X-rays that can de­tected by satel­lites or­bit­ing Earth, ac­cord­ing to Shin­suke Fu­jioka of Osa­ka Un­ivers­ity in Ja­pan, one of the re­search­ers in the new stu­dy.

But on Earth, photoi­on­ized plas­mas are much harder to pro­duce than con­ven­tion­al plas­mas, which are gas­es that that be­come charged as hordes of atoms col­lide with each oth­er or with sub­a­tom­ic par­t­i­cles called elec­trons.

To pro­duce a photoi­on­ized plas­ma, Shin­suke Fu­jioka and col­leagues used a 300 bil­lion watt la­ser to make a thin sil­i­con foil im­plode.

The re­search­ers found that the the X-ray spec­trum from the re­sult­ing plas­ma was re­markably si­m­i­lar to those meas­ured as em­a­nat­ing from the bi­na­ry stars Cyg­nus X-3—a star sys­tem be­lieved to house a black hole—and Ve­la X-1, a neu­tron star. Neu­tron stars are a type of highly com­pact star that share some black hole-like char­ac­ter­is­tics.

The re­sults al­so sug­gest con­ven­tion­al views as to how cer­tain parts of these spec­trums are formed could be wrong, Fu­jioka added. That could help as­t­ro­phys­i­cists im­prove their mod­els of black holes and si­m­i­lar as­t­ro­phys­i­cal sys­tems.

The Science

Oxford Catalysts designs and develops specialty catalysts for the generation of clean fuels, from both conventional fossil fuels and certain renewable sources such as biomass. Our patented technology is the result of almost 20 years of research at the University of Oxford’s prestigious Wolfson Catalysis Centre, headed by Professor Malcolm Green, one of the world’s most respected inorganic chemists. In essence, this patented technology facilitates the preparation and use of carbide-based catalysts, which can match or exceed the benefits of traditional precious metal catalysts for certain reactions (typically those involving hydrocarbons), whilst requiring predominantly only lower cost transition metals, such as cobalt and molybdenum. This technology incorporates a novel method for the preparation, activation and optimisation of the catalysts, the Organic Matrix Combustion Method, which allows better distribution of the active component on the catalyst support material thereby improving performance. Separately the technology from the University included an innovative catalytic process that enables the production of high temperature steam from a liquid fuel such as methanol mixed with water and an oxidising agent, such as hydrogen peroxide, instantaneously and starting from room temperature.

In November 2008, Oxford Catalysts completed the purchase of Velocys, Inc. from the Battelle Memorial Institute. Founded in 2001, Velocys is a leader in the field of microchannel process technology. This leadership began in the mid-1990s at Pacific Northwest National Laboratory, a U.S. Department of Energy facility operated by Battelle. From the mid-1990s through today, around $150 million has been invested into Velocys’ proprietary microchannel technology platform. Velocys’ chemical processors are characterized by parallel arrays of microchannels, with typical dimensions in the 0.1 to 5 mm range. Processes are intensified by decreasing transfer resistance between process fluids and channel walls. This structure allows use of more active catalysts than conventional systems, greatly increasing the throughput per unit volume. Overall system volumes can be reduced by ten to one hundred-fold compared to conventional hardware.

Combining Oxford Catalysts’ highly active catalysts with Velocys’ microchannel reactor technology has enabled the Company to develop a leading position, initially, in the race to demonstrate the commercial viability of small scale distributed biomass-to-liquid and gas-to-liquid technology.

The Commercial Use

Production of liquid biofuels such as diesel and jet fuel from organic materials including municipal waste is an attractive proposition. However, using conventional large scale plants requires bulky waste to be transported, often over long distances, negating some, if not all, of the environmental benefits. We are developing distributed production capability based on the use of small-scale, high intensity plants located close to the source of the waste. Microchannel reactors, combined with highly reactive Fischer-Tropsch catalysts optimised for use in these reactors are central to the distributed production approach. The plants will convert synthesis gas (syngas – a mixture of carbon monoxide and hydrogen produced by gasifying the biomass waste) into liquid fuels. A wide variety of carbon-containing materials, such as plant biomass-like crop residues and lignocellulose waste from trees, animal-derived waste, and municipal solid waste can be used as feedstocks. The Company is working with, amongst others, SCG Energia, the subsidiary of a Portuguese multinational, SGC.

Similarly, the inability to process natural gas produced in deep-sea oil recovery operations has resulted in flaring of the gas (or simply leaving the oil in the ground). Significant improvements in environmental impact, in addition to enhanced oil recovery can be achieved if the natural gas can be converted on board the FPSO (Floating Production Storage and Offloading) vessel to synthetic crude oil. High intensity modules for both reforming of methane to syngas and for Fischer-Tropsch synthesis are being developed for this application in partnership with MODEC (the world’s second largest supplier of FPSO’s) and Toyo, a major global engineering, procurement and construction company.

The Company

Oxford Catalysts’ business proposition following spin-out from the University of Oxford at the end of 2005 was attractive to institutional investors, resulting in an early IPO in April 2006, which raised a net £14M, followed by a further £4M in 2007. With the Company well capitalised, and with commercial interest in its developing technology increasing, Oxford Catalysts was well placed to acquire Velocys in 2008 in a reverse takeover. Since the acquisition, the combined Company has focussed on commercialising first its Fischer Tropsch technology, and recently announced that its first commercial test reactor (Velocys’ reactor with Oxford Catalysts’ catalyst inside) will be shipped to the well known eco-town, Güssing, Austria in December for demonstration starting in the first quarter of 2010. The Company is putting in place partners across the supply chain to commercialise its technology following successful demonstration.

Visit the Oxford Catalyst website here.

Download an information leaflet on Oxford Catalysts.

Sand can be hardened into sandstone in just a few days through the addition of bacteria. This could help to combat subsidence in houses, for example. Leon van Paassen has succeeded in scaling up the technique. He will defend his PhD thesis on Tuesday 20 October at TU Delft.

Chalk
Van Paassen’s PhD research focused on BioGrout, a new biological technique for reinforcing sandy soils. Within a few days, the sand hardens into sandstone. Specially cultivated bacteria cause calcium-carbonate precipitation in the sand.
Possible applications include railway stabilisation, stabilising pillars in the Limburg marl mines, and combating coastal erosion and housing subsidence.

Wedges
In his research, Van Paassen used Sporosarcina pasteurii, a bacterium that contains the enzyme urease. The bacteria are cultivated, injected into the ground and supplied with a solution of urea and calcium chloride. The enzyme urease catalyses the conversion from urea into ammonium and carbonate, whereby the carbonate precipitates as calcium carbonate crystals (chalk). These crystals form wedges between the grains of sand, increasing the strength and stiffness of the sand. The remaining ammonium chloride is then pumped out of the ground and disposed of.

Scaling up
Van Paassen, who is working in cooperation with the Deltares knowledge institute and contractor Volker Wessels, succeeded in scaling up the BioGrout process to an experiment of 100 cubic metres (a sand pit measuring 8 x 5 x 2.5 metres), in which the sand is hardened over a distance of five metres within 12 days.
However, there were a number of disadvantages to this method. Removing the ammonium chloride and using specific bacteria make the process relatively costly and therefore less interesting in terms of practical applications.

Alternatives
Van Paassen therefore researched possible alternatives to the original process. He discovered an interesting variant whereby calcium acetate (or other salts of fatty acids) and calcium nitrate are injected and converted by bacteria into chalk and nitrogen gas.
A main advantage of this new variant is that the work is done by naturally occurring bacteria and there is no ammonium chloride to be removed. Furthermore, in principle the initial substances calcium acetate and calcium nitrate can be extracted from waste.
Van Paassen demonstrated in experiments that the process actually occurs, but the technique has not been scaled up yet. The coming years will reveal how much potential the technique has.

Note for editors

For more information
Leon van Paassen; e-mail: L.A.vanPaassen@tudelft.nl
Research information officer TU Delft Roy Meijer, e-mail r.e.t.meijer@tudelft.nl
For more background information check: www.smartsoils.nl

A mysterious basin off the coast of India could be the largest, multi-ringed impact crater the world has ever seen. And if a new study is right, it may have been responsible for killing the dinosaurs off 65 million years ago.

Sankar Chatterjee of Texas Tech University and a team of researchers took a close look at the massive Shiva basin, a submerged depression west of India that is intensely mined for its oil and gas resources. Some complex craters are among the most productive hydrocarbon sites on the planet. Chatterjee will present his research at this month’s Annual Meeting of the Geological Society of America in Portland, Oregon, USA.

“If we are right, this is the largest crater known on our planet,” Chatterjee said. “A bolide of this size, perhaps 40 kilometers (25 miles) in diameter creates its own tectonics.”

By contrast, the object that struck the Yucatan Peninsula, and is commonly thought to have killed the dinosaurs was between 8 and 10 kilometers (5 and 6.2 miles) wide.

It’s hard to imagine such a cataclysm. But if the team is right, the Shiva impact vaporized Earth’s crust at the point of collision, leaving nothing but ultra-hot mantle material to well up in its place. It is likely that the impact enhanced the nearby Deccan Traps volcanic eruptions that covered much of western India. What’s more, the impact broke the Seychelles islands off of the Indian tectonic plate, and sent them drifting toward Africa.

The geological evidence is dramatic. Shiva’s outer rim forms a rough, faulted ring some 500 kilometers in diameter, encircling the central peak, known as the Bombay High, which would be 3 miles tall from the ocean floor (about the height of Mount McKinley). Most of the crater lies submerged on India’s continental shelf, but where it does come ashore it is marked by tall cliffs, active faults and hot springs. The impact appears to have sheared or destroyed much of the 30-mile-thick granite layer in the western coast of India.

The team hopes to go India later this year to examine rocks drill from the center of the putative crater for clues that would prove the strange basin was formed by a gigantic impact.

“Rocks from the bottom of the crater will tell us the telltale sign of the impact event from shattered and melted target rocks. And we want to see if there are breccias, shocked quartz, and an iridium anomaly,” Chatterjee said. Asteroids are rich in iridium, and such anomalies are thought of as the fingerprint of an impact.

Article Credit: AlphaGalileo

By breaking the human genome into millions of pieces and reverse-engineering their arrangement, researchers have produced the highest-resolution picture ever of the genome’s three-dimensional structure.

The picture is one of mind-blowing fractal glory, and the technique could help scientists investigate how the very shape of the genome, and not just its DNA content, affects human development and disease.

“It’s become clear that the spatial organization of chromosomes is critical for regulating the genome,” said study co-author Job Dekker, a molecular biologist at the University of Massachusetts Medical School. “This opens up new aspects of gene regulation that weren’t open to investigation before. It’s going to lead to a lot of new questions.”

As depicted in basic biology textbooks and the public imagination, the human genome is packaged in bundles of DNA and protein on 23 chromosomes, arrayed in a neatly X-shaped form inside each cell nucleus. But that’s only true during the fleeting few moments when cells are poised to divide. The rest of the time, those chromosomes exist in a dense and ever-shifting clump. Of course their constituent DNA strings are clumped, too: If the genome could be laid out end-to-end, it’d be six feet long.

For decades, some cell biologists suspected that the genome’s compression wasn’t just an efficient storage mechanism, but linked to the very function and interaction of its genes. But this wasn’t easy to study: Sequencing the genome destroys its shape, and electron microscopes can barely penetrate its active surface. Though its constituent parts are known, the genome’s true shape has been a mystery.

In April, a paper published in the Proceedings of the National Academy of Sciences linked patterns of gene activation to their physical proximity on chromosomes. It still provided the most persuasive evidence to date that genome shape matters, even though the researchers’ chromosome map was relatively low-resolution. The topography described in the latest research, published Thursday in Science, is far more detailed.

“It’s going to change the way that people study chromosomes. It will open up the black box. We didn’t know the internal organization. Now we can look at it in high resolution, try to link that structure to the activity of genes, and see how that structure changes in cells and over time,” said Dekker.

To determine genome structure without being able to directly see it, the researchers first soaked cell nuclei in formaldehyde, which interacts with DNA like glue. The formaldehyde stuck together genes that are distant from each other in linear genomic sequences, but adjacent to each other in actual three-dimensional genomic space.

The researchers then added a chemical that dissolved the gene-by-gene linear sequence bonds, but left the formaldehyde links intact. The result was a pool of paired genes, something like a frozen ball of noodles that had been sliced into a million fragmentary layers and mixed.

By studying the pairs, the researchers could tell which genes had been near each other in the original genome. With the aid of software that cross-referenced the gene pairs with their known sequences on the genome, they assembled a digital sculpture of the genome. And what a marvelous sculpture it is.

“There’s no knots. It’s totally unentangled. It’s like an incredibly dense noodle ball, but you can pull out some of the noodles and put them back in, without disturbing the structure at all,” said Harvard University computational biologist Erez Lieberman-Aiden, also a study co-author.

In mathematical terms, the pieces of the genome are folded into something similar to a Hilbert curve, one of a family of shapes that can fill a two-dimensional space without ever overlapping — and then do the same trick in three dimensions.

How evolution arrived at this solution to the challenge of genome storage is unknown. It might be an intrinsic property of chromatin, the DNA-and-protein mix from which chromosomes are made. But whatever the origin, it’s more than mathematically elegant. The researchers also found that chromosomes have two regions, one for active genes and another for inactive genes, and the unentangled curvatures allow genes to be moved easily between them.

Lieberman-Aiden likened the configuration to the compressed rows of mechanized bookshelves found in large libraries. “They’re like stacks, side-by-side and on top of each other, with no space between them. And when the genome wants to use a bunch of genes, it opens up the stack. But not only does it open the stack, it moves it to a new section of the library,” he said.

The segregation of active and inactive genes adds to evidence that genome structure affects gene function.

“It’s a great description of the structure of the nucleus, and if you put that on top of what we did, it forms the big picture,” said Steven Kosak, a Northwestern University cell biologist and co-author of the April PNAS paper that linked rough outlines of chromosome arrangement to gene activation. Whereas that study only looked at a few chromosomes, the Science paper “looks at fine resolution over the whole genome,” said Kosak.

“Now you can produce these genome maps, and superimpose them with genome-wide analyses of gene expression. You can really start asking how changes in spatial organization relate to changes in genes turning on and off,” said Tom Misteli, a National Cancer Institute cell biologist who studies how glitches in chromosome structure may turn cells cancerous. Neither Misteli nor Kosak were involved in the Science study.

Connecting genome shape to gene function could also help explain the connection between genes and disease, which remain largely unexplained by traditional, sequence-focused genomics.

“It’s perfectly reasonable and almost inevitable that the 3-D structure of DNA is going to influence how it functions,” said Teri Manolio, director of the National Human Genome Research Institute’s Office of Population Genomics.

Researchers also want to study how genome shape is altered. That appears to happen constantly during the transition from stem cell to adult cell, and then during cell function.

“How much variation is there in structure across cell types? What controls it? Exactly how important is it? We don’t know,” said Dekker. “This is a new area of science.”

[Image: From Science, a two-dimensional Hilbert curve, and the three-dimensional shape of a genome.]
Article Credit: Wired Science

What you will need:
A plastic bowl
PVA glue
Bottle of borax solution
Food colouring

Before you start
This is a messy activity, so cover the table you are using if it needs protection. Set the table so that you have all the liquids within reach. Children need a bowl and a spoon each. It is really important to try making some slime just before you start to check that it is the right consistency. You may want to get some small plastic bags for the children to keep their slime in – Ziploc bags are ideal.

The activity
This activity usually lasts between 10 and 20 minutes.

Start by putting two spoonfuls of water into the bowl. Add to this two spoonfuls of glue and mix until you get a consistent runny mixture (It does not have to be exactly two spoonfuls – two hefty dollops from heaped spoonfuls is close enough).
If you want coloured slime now is the time to add the food colouring – you only need a drop or two. You need to keep a careful eye on the colouring as it can stain clothes.
Mix the colour in and then add two spoonfuls of the borax solution. Ask the children to look carefully at the mixture as they stir it, noticing how it changes.
It will soon become a slimy blob. At this point take it out of the bowl and squeeze and knead it in your hands until it has become a complete slimy blob.
Continue to do this for a few minutes, and the slime should become dry (but still malleable). Do not worry if there is a little liquid left in the bottom of the bowl.

After the activity
Your slime is now complete. Is it a solid or a liquid? You can pull it apart quickly and it snaps in two like a solid, but will flow slowly like a thick liquid. If you pull it slowly apart it will just stretch. Try putting on top of your finger it will gradually surround it. If you drop a ball of slime it will bounce a little. Write or draw on a piece of paper with a felt pen. Then press your slime on it and it will lift the ink. If you press it on another piece of paper it may give a faint print.

The slime will soon start to stiffen as the water evaporates, but still remains slimy for some hours afterwards.

Science Notes
Children can observe the change in the consistency as they make their mixture. The slime is very good for informal testing and experimenting.

Scientists have managed to induce cells from pigs to transform into pluripotent stem cells – cells that, like embryonic stem cells, are capable of developing into any type of cell in the body. It is the first time in the world that this has been achieved using somatic cells (cells that are not sperm or egg cells) from any animal with hooves (known as ungulates).

The implications of this achievement are far-reaching; the research could open the way to creating models for human genetic diseases, genetically engineering animals for organ transplants for humans, and for developing pigs that are resistant to diseases such as swine flu.

The work is the first research paper to be published online today (Wednesday 3 June) in the newly launched Journal of Molecular Cell Biology [1].
Dr Lei Xiao, who led the research, said: “To date, many efforts have been made to establish ungulate pluripotent embryonic stem cells from early embryos without success. This is the first report in the world of the creation of domesticated ungulate pluripotent stem cells.

Therefore, it is entirely new, very important and has a number of applications for both human and animal health.”

Dr Xiao, who heads the stem cell lab at the Shanghai Institute of Biochemistry and Cell Biology (Shanghai, China), and colleagues succeeded in generating induced pluripotent stem cells by using transcription factors to reprogramme cells taken from a pig’s ear and bone marrow. After the cocktail of reprogramming factors had been introduced into the cells via a virus, the cells changed and developed in the laboratory into colonies of embryonic-like stem cells. Further tests confirmed that they were, in fact, stem cells capable of differentiating into the cell types that make up the three layers in an embryo – endoderm, mesoderm and ectoderm – a quality that all embryonic stem cells have. The information gained from successfully inducing pluripotent stem cells (iPS cells) means that it will be much easier for researchers to go on to develop embryonic stem cells (ES cells) that originate from pig or other ungulate embryos.

Dr Xiao said: “Pig pluripotent stem cells would be useful in a number of ways, such as precisely engineering transgenic animals for organ transplantation therapies. The pig species is significantly similar to humans in its form and function, and the organ dimensions are largely similar to human organs. We could use embryonic stem cells or induced stem cells to modify the immune-related genes in the pig to make the pig organ compatible to the human immune system. Then we could use these pigs as organ donors to provide organs for patients that won’t trigger an adverse reaction from the patient’s own immune system.

“Pig pluripotent stem cell lines could also be used to create models for human genetic diseases. Many human diseases, such as diabetes, are caused by a disorder of gene expression. We could modify the pig gene in the stem cells and generate pigs carrying the same gene disorder so that they would have a similar syndrome to that seen in human patients. Then it would be possible to use the pig model to develop therapies to treat the disease.

“To combat swine flu, for instance, we could make a precise, gene-modified pig to improve the animal’s resistance to the disease. We would do this by first, finding a gene that has antiswine flu activity, or inhibits the proliferation of the swine flu virus; second, we can introduce this gene to the pig via pluripotent stem cells – a process known as gene ‘knock-in’.

Alternatively, because the swine flu virus needs to bind with a receptor on the cell membrane of the pig to enter the cells and proliferate, we could knock out this receptor in the pig via gene targeting in the pig induced pluripotent stem cell. If the receptor is missing, the virus will not infect the pig.”

In addition to medical applications for pigs and humans, Dr Xiao said his discovery could be used to improve animal farming, not only by making the pigs healthier, but also by modifying the growth-related genes to change and improve the way the pigs grow.

However, Dr Xiao warned that it could take several years before some of the potential medical applications of his research could be used in the clinic.
The next stage of his research is to use the pig iPS cells to generate gene-modified pigs that could provide organs for patients, improve the pig species or be used for disease resistance.
The modified animals would be either “knock in” pigs where the iPS or ES cells have been used to transfer an additional bit of genetic material (such as a piece of human DNA) into the pig’s genome, or “knock out” pigs where the technology is used to prevent a particular gene functioning.

Commenting on the study, the journal’s editor-in-chief, Professor Dangsheng Li, said: “This research is very exciting because it represents the first rigorous demonstration of the establishment of pluripotent stem cell in ungulate species, which will open up interesting opportunities for creating precise, gene-modified animals for research, therapeutic and agricultural purposes.”

Contact (media enquiries only):
Emma Mason
Mobile: +44 (0)7711 296 986
Email: wordmason@mac.com

Researchers have used a common laboratory technique for the first time to detect genetic changes in embryos that could predispose the resulting children to develop certain cancer syndromes. Current preimplantation genetic diagnosis techniques can detect mutations in very small bits of genes or DNA, but, until now, it wasn’t easy to detect deletions involving whole genes or long sections of DNA in embryos.

The study, published online today (Wednesday 11 March) in Europe’s leading reproductive medicine journal Human Reproduction [1], uses a technique called fluorescent in situ hybridization (FISH) to detect losses of small parts of whole chromosomes (microdeletions) in a single cell from an embryo. The work opens the way to test for microdeletions in patients with other genetic conditions as well as the two cancer predisposition syndromes treated in this study. [2]

Professor Joris Vermeesch, coordinator of the Genomics Core and head of Constitutional Cytogenetics, and Evelyne Vanneste, a PhD student, both at the Center for Human Genetics, University Hospital Leuven (Belgium), and their colleagues used FISH to carry out PGD in embryos from three couples where the women carried microdeletions for either neurofibromatosis type 1 (NF1) or Von Hippel-Lindau disease (VHL). As a result, the woman with the VHL mutation gave birth to healthy twins from embryos selected using FISH PGD.

Neurofibromatosis type 1 (also known as Von Recklinghausen disease) is a common inherited condition with an incidence at birth of one in 3,000-3,500. NF1 patients develop tumours of the nervous system, pigmented patches of skin and can have lower IQs. In 95% of people with NF1, a mutation is found in the NF1 gene, which is a tumour suppressor gene; but five per cent of NF1 patients have microdeletions of the gene, and large microdeletions can result in more severe symptoms.

Von Hippel-Lindau (VHL) disease is a rarer cancer syndrome, occurring in about one in 36,000 births. Symptoms of the disease include benign tumours of the central nervous system and benign and malignant tumours of organs such as the kidneys, adrenal glands and pancreas. It is an inherited condition caused by a mutation in the VHL tumour suppressor gene.

The strands of DNA that twist together to form the double helix structure are made up of lots of small sections called nucleotides. The nucleotides are made up of the four DNA bases – adenine, thymine, guanine and cytosine (or A,T,C,G). Mutations that can be detected by the conventional PCR (polymerase chain reaction) technique used in PGD are usually mutations of a single nucleotide or base. A deletion or microdeletion normally involves the loss of larger numbers of nucleotides.

Prof Vermeesch explained: “Current techniques using PCR to detect abnormalities in embryos can detect one base, nucleotide or letter change in the DNA, but they cannot be used when a person has a loss of the whole gene or a lot of letters – a microdeletion. Patients with these cancer predisposition syndromes, and some other conditions, usually carry only a single microdeletion. Now, for the first time, we have used FISH to detect these microdeletions in the embryo and thus can help carriers to create offspring without those anomalies.

“Importantly, microdeletions are not so rare in neurofibromatosis type 1. It is also becoming clear that genomic disorders caused by microdeletions, duplications and copy number variations are much more frequent than previously thought. The techniques we have used in this study will help a wide range of microdeletion carriers.”

For each of the three women, the researchers created probes that could be used to identify NF1 or VHL deletions in the embryos. The embryos were obtained from the women using normal assisted reproduction techniques. They took two cells from each embryo and performed FISH to probe them for the microdeletions. Only embryos that FISH had identified as being healthy, without any microdeletions, were transferred to the women’s wombs.

Ms Vanneste explained that although they had to make FISH probes specific to each woman, the NF1 microdeletions found tended to recur. “Therefore, most NF1 patients with a deletion carry the same deletion and our FISH PGD conditions can be rapidly replicated and re-used in other deletion carriers. It seems likely that the number of families that can benefit from FISH PGD will increase in years to come and we are continuing to help more families using this approach. However, for each condition a new probe has to be made. This is time-consuming, but we are currently developing tools to identify all similar genetic imbalances with a single technology.”

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Scientists have created the final predicted form of stable ice, called ice XV, in the lab. But don’t worry — Kurt Vonnegut had nothing to do with it, and the exotic new form of ice can’t destroy civilization.

Types of ice are classified by how close the water molecules pack together and the structure the molecules arrange themselves in. With the new discovery, researchers have identified 16 forms of ice (including two types of ice I) named in order of discovery. Most of the ice on Earth is type Ih (h for hexagonal, hence the six-sided symmetry of all snowflakes). Researchers had long predicted the existence of ice XV, but had never seen it before.

“We have removed the question mark from the phase diagram of water,” says Christoph Salzmann of the University of Oxford in England, coauthor of a paper published online September 2 in Physical Review Letters. A phase diagram maps how molecules will behave at certain pressures and temperatures.

To create the elusive ice, Salzmann and his colleagues dropped the temperature on another kind of ice, ice VI, in which water molecules are bonded to each other willy-nilly. As the researchers lowered the temperature to 130 kelvins (around -143º Celsius) and held the pressure around one gigapascal (almost 10,000 atmospheres), disordered hydrogen bonds in ice VI snapped into a highly ordered, tight conformation and created ice XV. Ice on Earth is downright fluffy in comparison with the newly discovered ice XV.

Earlier predictions guessed that ice XV might be ferroelectric, possessing the ability to carry a charge. Ice with that property could have had interesting effects on geological events on planets, Salzmann says. Instead, water molecules in ice XV pack in such a way that the charges all cancel out.

Ice XV’s stability at high pressures and low temperatures may allow it to exist somewhere out in the cosmos—maybe in deep interiors of icy planets or moons, Salzmann says. The only places on Earth with high enough pressure to sustain ice XV are also extremely hot, so ice XV can’t form there, he says.

Ice IX, made fictionally famous by Vonnegut in Cat’s Cradle, also exists only under high pressure.

[Image Credit: Flickr/darrenhester.]

Article Credit: Wired Science

Together with three colleagues Professor Peter Oppeneer of Uppsala University has explained the hitherto unsolved mystery in materials science known as ‘the hidden order’ – how a new phase arises and why. This is a discovery that can be of great importance to our understanding of how new material properties occur, how they can be controlled and exploited in the future. The findings are now being published in the scientific journal Nature Materials and of great importance to future energy supply.

For a long time researchers have attempted to develop the superconducting materials of the future that will be able to conduct energy without energy losses, something of great importance to future energy supply. But one piece of the puzzle has been missing. There are several materials that evince a clear phase transition in all thermodynamic properties when the temperature falls below a certain transitional temperature, but no one has been able to explain the new collective order in the material. Until now, this has been called the hidden order.

“The hidden order was discovered 24 years ago, and for all these years scientists have tried to find an explanation, but so far no one has succeeded. This has made the question one of the hottest quests in materials science. And now that we can explain how the hidden order in materials occurs, in a manner that has never been seen before, we have solved one of the most important problems of our day in this scientific field,” says Professor Peter Oppeneer.

Four physicists from Uppsala University, led by Peter Oppeneer and in collaboration with John Mydosh from the University of Cologne, who discovered the hidden order 24 years ago, show through large-scale calculations how the hidden order occurs. Extremely small magnetic fluctuations prompt changes in the macroscopic properties of the material, so an entirely new phase arises, with different properties.

“Never before have we seen the so-called ‘magnetic spin excitations’ produce a phase transition and the formation of a new phase. In ordinary materials such excitation cannot change the phase and properties of the material because it is too weak. But now we have shown that this is in fact possible,” says Peter Oppeneer.

What explains in detail all of the physical phenomena in the hidden order is a computer-based theory. Among other applications, it can be used to better understand high-temperature superconducting materials and will thus be important in the development of new superconducting materials and our future energy supply.

Article Credit: AlphaGalileo

Ecstasy may help suffers of post-traumatic stress learn to deal with their memories more effectively by encouraging a feeling of safety, according to an article in the Journal of Psychopharmacology published today by SAGE.

Studies have shown that a type of psychological treatment called exposure therapy – where the patient repeatedly recalls the traumatic experience or is repeatedly exposed to situations that are safe but still trigger their traumatic feelings – can be effective in relieving stress responses in patients with post-traumatic stress disorder (PTSD) and other anxious conditions. The therapy works by helping the patient to re-learn the appropriate response to the trigger situation, a process known as extinction learning.

But this approach can take some time, and 40% of patients continue to experience post-traumatic stress even after their treatment. To improve outcomes, scientists have been investigating the use of drug therapies to enhance the effect of exposure therapy, making the result of exposure to the fear trigger easier, faster, and more effective. MDMA (the pharmaceutical version of Ecstasy) is one such drug.

“A goal during exposure therapy for PTSD is to recall distressing experiences while at the same time remaining grounded in the present. Emotional avoidance is the most common obstacle in exposure therapy for PTSD, and high within-session emotional engagement predicts better outcome,” explain authors Pål-Ørjan Johansen and Teri Krebs, who are based at the Norwegian University of Science and Technology and supported by the Research Council of Norway.

Psychiatrists that have administered MDMA to anxiety patients have noted that it promotes emotional engagement; strengthens the bond between the patient and doctor, known as the therapeutic alliance; decreases emotional avoidance; and improves tolerance for recall and processing of painful memories.

According to Johansen and Krebs, “MDMA [ecstasy] has a combination of pharmacological effects that…could provide a balance of activating emotions while feeling safe and in control.”
They suggest three possible biological reasons why ecstasy could help individuals with PSTD. First, ecstasy is known to increase the release of the hormone oxytocin, which is involved in trust, empathy, and social closeness.

Because people with PTSD often report feeling emotionally disconnected and unable to benefit from the supportive presence of family and friends or therapists – a situation that is likely to contribute to the development and maintenance of the disorder – use of ecstasy might also help ameliorate these symptoms, suggest the authors.

“By increasing oxytocin levels, MDMA may strengthen engagement in the therapeutic alliance and facilitate beneficial exposure to interpersonal closeness and mutual trust,” they write.

The second biological explanation for ecstasy’s useful effect is that it acts in two brain regions to inhibit the automatic fear response (mediated by the amygadala) and increase emotional control (mediated by the ventromedial prefrontal cortex) and therefore permits bearable revisiting of traumatic memories.

Thirdly, ecstasy increases the release of two other hormones, noradrenaline and cortisol, which are known to be essential to trigger emotional learning, including the process that leads to fear extinction, on which therapy for PTSD relies. But, caution the authors, while these compounds enhance extinction learning they may also temporarily increase anxiety in people with PTSD because the hormones are naturally released as part of the body’s response to stress.

Ecstasy combined with psychotherapy is a treatment already being tested in clinical trials to help patients with PTSD. All of these trials have a similar design in which ecstasy or placebo is administered to patients a few times during their therapy sessions as part of a short term course of psychological treatment. According to the Johansen and Krebs, recent preliminary results from two of these randomized controlled trials shows that the therapy might have promise.

“Reduction of avoidance behavior linked to emotions is a common treatment target for all anxiety disorders. MDMA [ecstasy] has a combination of pharmacological effects that, in a therapeutic setting, could provide a balance of activating emotions while feeling safe and in control, as has been described in case reports of MDMA augmented psychotherapy….Future clinical trials could combine MDMA with evidence-based treatment programs for disorders of emotional regulation, such as prolonged exposure therapy for PTSD,” conclude the authors.

Article Credit: AlphaGalileo