‘The Atom’ at Science Oxford Live used the music of Bach played on a violin to illustrate atoms and energy. This seemed appropriate to me as know Bach means ‘small in Welsh’. Atoms are the smallest particle of a pure substance that can be told apart (classed as an element). The numbers, ratio and formation of even smaller entities such as, protons, neurons, electrons and quarks determine how the atoms will interact and combine with others to form molecules.

At this tiny scale, nothing stays still. Tiny particles are randomly moving and colliding, known as ‘Brownian motion’. This is faster in liquids than solids and faster still in gases, and increases with temperature.
Forces of attraction determine how atoms and molecules combine and the kind of structures they form, holding them together despite the Brownian motion. This in turn influences material properties, for example how hard, soft, brittle or rubbery we experience them to be.

Humans like to experiment with movements of atoms to create new substances and molecular structures. The large Hadron collider using magnetic force to accelerate and collide materials and is capable of generating completely new atoms, heavier than those seen in nature.

Nano technology has developed from systematically combining molecules in machine like assemblies, generating tiny structures, designed to move in a specific way or interact to serve a particular purpose, a bit like tiny gears and leavers. The cohesive forces and motion mean that substances used have be carefully selected and spread out into thin layers to elicit the desired behaviour.

Structures are built up, 2D and then 3D and combined. They can self assemble to form designed combinations where joints can be broken and remade (e.g sticky ends). This produces ‘shape shifters’ and ‘walkers’ with defined ways of generating their own motion, for example an extremely tiny ‘inch worm’ Ω.

Nano is a Greek word meaning, dwarf or very small. Just one millimetre is equivalent to one million nanometres. Professor Ned Seeman takes inspiration from Greek architecture creating these elaborate designs. DNA can be used as a nanoparticle, to build complex architectural structures (macromolecules) by manipulating the way strands combine.

Nanotechnology can be used for things such as incredibly tiny electronic circuitry in an IPOD, improved coatings to avoid rust, non stick surfaces and even in to improve interactions between skin and materials for example in sports training shoes and even ballet dancers pointe shoes, to protect from infection.
There is a lot of talk about the revolutionary potential of Nanotechnology. Should we worry? Very small particles can easily pass through bodies defences, get inside cells and interact with their natural machinery – great in terms of medicine and creams to nourish skin. Problems come if particles made for another reason are found to be harmful to people, wildlife and the environment and accidently escape or fall into the hands of someone wanting to cause harm.

This futuristic technology makes the ponderings of ancient Greeks philosophers more relevant than ever. When it comes to deciding whether to accept a technology, getting to grips to grips with classic fundamental questions like, ‘where is the boundary between our body and the world outside our body’, ‘what makes us who we are?’ and ‘how should we direct the things we make?’, is a very good place to start.

Soft Machines, Nanotechnology and Life Prof RAL Jones, http://www.softmachines.org/wordpress/

Prof Nadrain Seeman, http://seemanlab4.chem.nyu.edu/

I am an enzymologist, and so study the chemistry, function and mechanisms of enzymes. For many of you, the word enzyme will probably ring a bell and take you back to school biology and the lock and key theory of substrates ‘clicking’ into a matching enzyme active site. But what exactly is an enzyme?

Basically, enzymes are proteins. Proteins in turn are long chains of amino acid monomers. There are twenty naturally occurring amino acids, all with the same backbone structure but with chemically varied side-chains. Although there are some exceptions in the remnants of what is thought to have been a chemically simpler RNA-based world prior to the evolution of protein and DNA, proteins provide the ‘machinery’ of living cells, with their roles ranging from structural support to catalysis.

Enzymes are a sub-group of proteins which are biological catalysts that help specific biochemical reactions to proceed at a faster rate. Although many biochemical reactions do occur in the absence of enzymes under extreme conditions, they would only happen very slowly at physiological pH and temperature. The half-times of the uncatalysed reactions can be millions of years, so if Nature depended on reactions taking place without catalysis, life as we know it would simply not be possible.

My research is into the activity of an enzyme called flap endonuclease, which acts a bit like a pair of molecular scissors that cut a DNA strand at a structurally defined position. Whilst DNA breakages in general are likely to be a bad thing because they can lead to mutations, it is important to remember that controlled cleavage is absolutely essential for cells to be able to replicate and repair DNA, because both damaged sites and primers initiating DNA synthesis have to be removed. This is where our particular enzyme, flap endonuclease, comes in.

So how can we go about trying to work out the cutting mechanism? In the protein world, it is the amino acid side-chains that provide the functionality of the enzyme, sometimes supplemented by co-factors such as vitamins and minerals from our diet. Using the earlier machinery analogy, the amino acid side-chains and key chemical groups of the co-factors can be likened to levers and cogs. However, unlike real machinery, proteins are too small to see so we have to design indirect experiments to work out where the levers are and what they do.

One option is to determine their structure by the use of X-ray crystallography or NMR spectroscopy. Nevertheless, such structural studies only provide a static picture, like seeing the machine stopped and not knowing how the levers move. In addition, enzyme structures are often determined in the absence of reactants and products so do not tell us how these molecules fit in. This is where enzymologists have work to do, carrying out solution studies to further develop mechanistic knowledge about the activity of enzymes. Unlike many other proteins, with enzymes there is usually a way of measuring the appearance of a product or disappearance of a reactant, thus allowing us to measure the enzyme efficiency. Subtly changing the conditions of the reactions – which may be by mutation of one or more of the amino acids to change the shape of a particular ‘lever’, or by changing the pH of the reaction to alter the level of protonation and therefore the state in which the ‘levers’ are in – and then comparing the rates at which each reaction proceeds can tell us something about how an enzyme catalyses the reaction.

Finally, you may ask yourself why we should spend time investigating how enzymes work. A better understanding could potentially provide new leads for the pharmaceutical industry. Some enzymes can be malfunctioning or missing, or conversely over-produced, in diseased as compared to healthy cells. It could be possible to play molecular Lego and fill in the missing or broken bits using small drug molecules to restore or inhibit function, a process which clearly becomes much easier if we know how the enzyme works.

In so many newspaper articles about scientific and technological discoveries, you find the phrases “researchers showed”, “scientists suggest” and similar. Many lay readers will associate a scientist with a white coat and possibly a bearded old man, but is this really true? In my view, this image is really rather outdated and although I do wear a white coat when doing my lab work, I also do much other stuff in my daily life as a biochemist/protein scientist/enzymologist. Nevertheless, the fact remains that most members of the general public do not really know what a scientist does (even my parents, when asked to describe what I do, are often stumped to do this). So here’s my attempt at explaining what the daily life of a scientist might actually involve.

Unlike a growing number of researchers in the field of bioinformatics, where much work is done by analysis of the growing amount of data (from the humane genome project, from proteomics, metabolomics, microarrays and other fields that produce data in high-throughput fashion) with the help of powerful computers, I still do what is called ‘wet work’. This means I get to spend some time at the bench, mixing solutions and seeing what happens to them after you mix them. To put it very simply. As I am an enzymologists, I work with very tiny things, that you can’t even see under a microscope, so much of my lab work involves mixing colourless solutions with other colourless solutions (if I’m lucky, something that contains metal ions or fluorophores might be green, yellow or pink!) of microlitre quantities (a microlitre is a thousandth of a millilitre and you have about 500 millilitres of liquid in your pint glass) in small tubes of about 1.5 mL. Because I can’t see directly what is happening in my experiment, I have to have indirect ways of monitoring the readout of my experiment. In the past, this has involved looking at the changes in fluorescence (fluorescence happens when you shine a light onto your sample and it emits light of a different wavelength which you can measure, which requires the sample to contain a fluorophore) and more recently I have looked at the chopping up of DNA strands to give me a set of radioactive products which can be quantified because of the radioactivity readout.

On an average day, I will usually spend the morning and first part of the afternoon doing the experiments that were designed, more often than not, on a previous day so that I can get straight into it and get it done. Once finished, the experiments have to be analysed – in the past I have used a machine called a denaturing HPLC which did this for me. This was great, because you put your samples on, started the analysis programme and came back the next morning to get your results. But on the downside, it meant that all of us in the group were using the same instrument and time on it was pretty precious. These days, I analyse my experimental samples (which are effectively DNA fragments of different sizes) by running them on a gel, which separates them based on size (the shorter fragments run more quickly, because they don’t get stuck in the matrix that is the gel). And the gels can then be exposed by putting them in a light-tight cassette together with photographic film, which when developed, show you the location of the DNA fragments of different sizes.

And voila, here’s your result. Well, nearly, what comes next is the analysis phase and I generally spend some time in the afternoons analysing my data and working out what the images actually mean, which is as important, if not more so, as doing the experiments in the first place. So I get to work out what my data means and then promptly go on to design the next experiment based on it to ask the next question or repeat the observation I’ve just made so that I can be sure your result is not just a fluky one-off that happened because of one particular set of conditions and that cannot be actually repeated.

Which all sounds very simple and you might ask yourself whether all scientists have such an easy life. Well, it’s not quite all that we do. In theory, all the experiments work very well and you get a result from them that tells you something useful. In practice, not every experiment is conclusive, perhaps because there was something wrong with the buffer (the solution added to the experimental set-up to make the conditions as constant as possible), the enzyme you were adding has gone off or you forgot to add a component (it does happen even to the best of scientists!). Or the machine that you were going to use to analyse your data has been broken and you need to wait for it to be fixed. Or your reaction component has run out and the person who finished it didn’t order it at the time so you’re now waiting for a delivery. Or the fire alarm went as you were taking the critical time-points so you had to evacuate the building and start the experiment all over again. What I’m trying to say is that not every experiment is going to be usable so whilst it would be nice to think that everything you do will end up being part of that Nature paper, it is regrettably not so…

Which brings me to an important aspect of being a scientist, and that is the need to disseminate and publish your results. This is a key part of a scientist’s daily life, because, if the work is simply filed in your lab-book, there’s no point in doing it in the first place. You need to get others to hear about it so that they can repeat the work and build on it in their own research. Therefore being a scientist requires some time to be spent on reading other papers (for background and to work out how your work fits in with the work of others – but hopefully you’ve already spent some time reading the papers when you started the project!) and writing manuscripts to be sent to academic journals for peer review. Sometimes you are trying frantically to get things done in time for a deadline or because you know another group is working on the same problem and you do not want to be ‘scooped’, meaning that they publish their results first, leaving you to publish in a journal with a lower impact factor or, worse, not being able to publish at all because the work is no longer novel enough. Not only is the writing required but once the peer reviewers get back to you, more often than not they will have come up with some more experiments for you to do in order for them to find the paper acceptable. Often, this means you have a very short period to do the experiments which means you have to quickly reprioritise your time in the lab and try and deal with those things first, above everything else that you may have been working on. Of course, if you get senior enough/experienced enough in your field of expertise, you might yourself get asked to peer review papers, which is seen as part of a scientist’s responsibility to the community.

Whilst doing all the lab-work and data analysis, paper writing and dealing with referees comments, you will also have other responsibilities. Apart from perhaps being in charge of the upkeep of certain instruments (if you’re lucky to be in a large department, you may have a lab manager to do this), many departments run seminars where people regularly give talks about their ongoing work, and very often your turn ends up being at a time when you are most busy in the lab. (This is called Murphy’s Law, I think, but not scientifically proven). Other talks that you may be giving include sessions with your own lab/group, where the data is possibly taken apart more thoroughly, but which are often very useful because you get genuine feedback and are able to work out new avenues to explore in your research.

Openness and willingness to share data is a great thing in science and this is what leads to some useful discussions at conferences. Conferences have speaker sessions, where participants give talks about their data (or their group’s data, if it is the lab-head speaking), and poster sessions where individual researchers present their research in poster format, chatting informally to other conference participants who may be able to provide feedback. Conferences are great places to reinvigorate your interest in science in general and get excited about what goes on in other parts of the scientific world (when working in the lab, the daily grind can often be a bit repetitive and tedious, so it’s good to get out and talk to others and find that they’re all in the same boat). Of course they take a bit of preparation and in the run up to the conference you need to write an abstract to explain what you plan to present (often about 3 months before the actual conference so you need to be vague enough to fit in all the data that you may yet get in the next few weeks) and just before-hand you need to prepare your talk or poster (not forgetting that getting the University printers to print it the night before your 6am flight is just not an option!).

So I guess it is all very varied even if there is some sort of regularity to my average lab day. If I had any recommendations to budding scientists, I would say you should be prepared to change the plans and improvise if last minute requests come in for something urgent. But then most jobs are like that, right? I hope I’ve given you a bit more of an insight of what a lab-based scientist like me does. If you’re interested in the details, see below for a link to some information about the peer review process and, totally unrelated, a slightly tongue-in-cheek parody of Lady Gaga’s Bad Romance song describing the difficulties of being a PhD research student in biology.

Some useful links:
Something about the peer review process: http://www.senseaboutscience.org.uk/index.php/site/project/29/
A tongue in cheek parody of life in the lab (not everyone feels like this, I promise!): http://www.youtube.com/watch?v=Fl4L4M8m4d0

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.”

Contact (media enquiries only):
Emma Mason
Tel: +44 (0)1376 563090 Mobile: +44 (0)7711 296 986
Email: wordmason@mac.com