Shaken not stirred - how to extract your own DNA

Last week I eagerly sat down to watch the first episode of a new series: Dara O Briain's Science Club. For those of you from outside the British Isles, Dara O Briain is an Irish comedian who, in recent years, has become one of the most popular comedians and broadcasters in the UK. Not only is he a very funny guy, he's also got a pretty sharp mind inside his (frankly massive) shiny head: he studied mathematics and theoretical physics at University College Dublin and has managed to hang on to his love of science despite moving into the world of entertainment. He, along with other big names like Brian Cox and James May, has been instrumental in advancing British popular science broadcasting in the last decade and has presented a number of science programmes, such as School of Hard Sums and Stargazing Live, giving science that much-needed welcoming and friendly face. 

His new series is most definitely worth watching and I await the next episodes with bated breath. The first was on the subject of genetics and epigenetics and my curiosity was more about how these complex topics would be presented rather than actually learning something (I'm already fairly familiar with the fields)! I was delighted by the casual and approachable way in which it was structured, and how debates about scientific funding and application were mixed in with the hard facts. 

Possibly my favourite moment, however, was when we were shown how to perform a simple task that I am very used to doing in the lab, but in your own home: extracting DNA. Perhaps appropriately given the latest addition to the James Bond franchise, this entailed the use of cocktail-making equipment and the kind of very strong vodka needed to make that perfect Martini. Some might think of this as a big gimmicky and irrelevant, but I quite like the idea of making somewhat abstract scientific principles more tangible in the mind of the general public. Bringing such a standard research procedure into people's homes helps to demystify the scientific method and hopefully give people a greater sense of ownership over this work than they might otherwise have.

So, today's post is a shameless plug for Dara O Briain's Science Club with the aforementioned DNA recipe thrown in for those of you unfortunate enough not to be able to watch it online! Enjoy.



1. Collect some of your cheek cells by swishing some (around 100ml) salt water around your mouth for 30 seconds or so. The solution will be a bit cloudy afterwards.

2. Add a few drops of washing-up liquid (to dissolve the cells' membranes) and a shot of pineapple juice (the proteases in this will degrade the myriad proteins found in your cells). Pop it all into a cocktail shaker and give it your best shake!

3. Pour through a cocktail strainer to remove bubbles, ideally into a martini glass or something in which it's easy to layer different liquids.

4. Chill some very strong (>80% abv) vodka on ice and they carefully layer over the top of your mushed up cell solution. At such a high concentration of alcohol DNA comes out of solution and so precipitates at the boundary between the two solutions. This looks like a white cloud forming at the bottom of the vodka layer, which can be scooped out by wrapping it around a toothpick or something similar. Et voilà! It may not look like much, but you have successfully extracted the chemical instructions that make you you. Not bad for 5 minutes work.

Science and Video Games

A long time ago I posted about an online game called FoldIt. After I made that post various other examples of crossovers between video games and science have been brought to my attention. Many of these, I have linked to from The Trenches of Discovery's Facebook and Google+ pages and some I've been saving for a rainy day. (Note, we often post links/comments to those pages when we don't consider them worth a whole blog post. If you read this blog, but aren't following either of those pages, you're missing out on some interesting stuff. You should remedy this.)

Well, it isn't rainy, but it is foggy, so the day has as good as come. What follows is a run through of some of the various science/video game crossovers I'm aware of. Some of these are neat video games, designed to either teach an aspect of science, or  try to give a phenomenological experience of what that aspect of science means for the world. Others are more like FoldIt, they are puzzle games that you try to solve, and in the process you're actually helping the scientists solve their research problems.

Phylo

The 2012 Nobel Prize in Physics: The background

[The following is a guest post from Simon Thwaite. Simon recently completed his doctorate in the subdepartment of Atomic & Laser Physics at the University of Oxford. He is currently in the limbo that lies between the submission of a doctoral thesis and its examination, and is looking forward to taking up a postdoctoral research fellowship in the Theoretical Nanophysics group at the Ludwig Maximilian University, Munich, from January 2013.

In Part 1 of this post he discusses the foundations of the field of atomic, molecular, and optical physics, and describes the process of laser cooling, an experimental technique for cooling atoms to extremely low temperatures. This technique forms the foundation for many of the current experiments in the field.

In Part 2 of this post he describes the experiments carried out by Haroche and Wineland, and discusses the possible applications and future directions of their work.]

2012 Nobel Laureates in Physics Serge Haroche (left) and David J. Wineland (photo credit: CNRS, NIST).

The 2012 Nobel Prize in Physics: score one more for AMO physics

Those with their finger on the physics pulse will have seen that the 2012 Nobel Prize in Physics was recently awarded jointly to Serge Haroche and David J. Wineland for their development of "ground-breaking experimental methods that enable measuring and manipulation of individual quantum systems". This announcement raises a number of questions for physicists and physics followers alike: what is meant by an ‘individual quantum system’, and why would anyone want to measure and manipulate such a thing? What kind of experiments do Haroche and Wineland do, and what new scientific and technological possibilities does their research unlock? And -- last but not least -- will Prof. Wineland be involved in the imminent month of Movember? Because if he is, everyone else might as well just go home right now.


Atomic, molecular, and optical physics: a brief history

The research of Haroche and Wineland falls within the field of atomic, molecular, and optical (AMO) physics, which studies how particles of matter (atoms, ions, and molecules) interact both with one another and with particles of light (photons: see figure), and how these interactions can be controlled and exploited to engineer systems of particular scientific or technological interest. AMO physics is currently a highly active and dynamic area of research, with applications which range from questions of fundamental scientific interest (e.g. is it possible that the fine structure constant is actually changing slowly with time?) through to real-world technologies (e.g. the development of ultra-precise atomic clocks for the definition of universal time and frequency standards). It has also enjoyed somewhat of a Golden Age in recent years, with the 2012 Nobel Prize in Physics being the third in the last 15 years (after 1997 and 2001) to be awarded for work in the field.

The physical theory that governs the world in the ultra-small regime of atoms, molecules, and photons is the theory of quantum mechanics, which describes both the behavior of these individual quantum systems and the way in which they interact. The roots of AMO physics can thus be traced back to the early part of the 20th century, when quantum mechanics was developed in the course of the search for a better understanding of such phenomena as the radiation emitted by hot objects and the internal structure of atoms.

A rough sketch of an atom (not actual size).    

The electrons orbiting the nucleus are only 

permitted to occupy a certain discrete set of 

energy levels.

Building on the theory of quantum mechanics, the state of atomic physics improved at a breathtaking pace throughout the first half of the 20th century. In contrast, research into the ‘optical’ part of AMO physics progressed at a more sedate pace. While much of the required theoretical knowledge already existed – the wave theory of light and the electronic structure of atoms both being well-understood by this point – rapid progress in any field requires interaction between theory and experiment, and the absence of any technology that could produce a focused, powerful, and wavelength-specific (i.e. single-colour) source of light severely restricted the sophistication of possible atom-light experiments.

This state of affairs changed drastically with the invention of the laser in the early 1960s. Developing out of radar and microwave research carried out during the Second World War at Bell Laboratories, lasers provided a light that was radically different from anything seen before: in addition to containing only a single pure wavelength, laser light is well collimated (i.e. forms a well-defined beam) and can easily be millions of times more intense than any other light source. At a stroke, the door was opened to a whole range of possible new atom-light experiments, ushering in a new era in the discipline of atomic, molecular and optical physics.

Laser light can be viewed as either a travelling electromagnetic wave (left) or a stream of photons (right).

Laser cooling: the beginning of the Golden Age

One particularly striking demonstration of the possibilities that laser light provides for controlling and manipulating atoms has been the development of laser cooling: using tightly-focused beams of laser light to slow down, or cool, a collection of atoms in a gas. Developed throughout the 1980s and recognized with the 1997 Nobel Prize in Physics, laser cooling is today ubiquitous in a wide range of AMO physics experiments, and forms the foundation for the fertile subfield of ultracold atoms.

But you thought lasers could only heat things up, or burn holes in them? Then read on. 

The atoms in a gas at room temperature move about very rapidly (their speed depends on the temperature of the gas, but in any case is of the order of several hundred metres per second). Now imagine that you’re an experimental physicist, and your goal is to manipulate and interact with these atoms in some kind of precise, controlled way -- for example, you might want to carry out some spectroscopy on them in order to measure the exact frequencies of light that this atomic species absorbs and emits. In this case, working with a ‘hot’ gas of rapidly-moving atoms is far from ideal -- in fact, it’s a complete disaster. Since the atoms are moving reasonably quickly, the radiation they absorb and emit is subject to a significant Doppler shift, making precise frequency measurements impossible. Further, the atoms collide both with one another and with the walls of their container, and these collisions lead to an additional ‘smearing out’ of the frequencies emitted or absorbed by each atom.

These problems could be largely nullified if only the atoms in the gas could be slowed down, or even brought to a complete stop. The great discovery of the 1980s and early 1990s was that this can be achieved by using laser light of a carefully-selected frequency to manipulate the atoms in the gas. Like many of the best achievements in science, the basic idea is both simple and elegant: a rapidly-moving atom is gradually slowed down by bouncing a stream of photons off it, one after another. Although each photon takes only a small amount of momentum away from the atom, the absorption and re-emission of a photon takes place in less than a microsecond, so that a single atom can scatter over a million photons every second. Consequently, an atom can be slowed down from a speed of several hundred metres per second (corresponding to room temperature) to a near-complete standstill in only a few thousandths of a second. These laser-cooled atoms -- which are at a far lower temperature than anything found in nature, even in the deepest depths of outer space -- can now be measured, probed, and further manipulated with an extremely high degree of accuracy.

The process of laser cooling: by arranging a set of lasers such that they remove momentum from the rapidly-moving atoms in a room-temperature gas, clouds of up to a few tens of millions of atoms can be cooled down to temperatures of less than a millionth of a degree above absolute zero .

[If you'd like to try out laser-cooling for yourself, the University of Colorado at Boulder has made a fantastic series of interactive Java applets that describe the process very well.]

Together with the invention of related techniques for trapping clouds of laser-cooled atoms using combinations of laser light and magnetic fields, the development of laser cooling stimulated a frenzy of new activity in atomic, molecular, and optical physics. Since the early 1990s, the level of experimental control in cold-atom experiments has progressed to the point where it is now routine to isolate, trap, and cool either individual atoms, or clouds of up to a few tens of millions of atoms, to temperatures of a few hundreds of nanoKelvin (billionths of a degree above absolute zero) in a controlled and repeatable fashion.  These new experimental capabilities have found applications in a diverse range of topics, which span all facets of atomic, molecular, and optical physics. Two such topics in which laser cooling plays an integral role – namely, the interaction of laser-cooled atoms with light trapped between two very small mirrors, and the interaction of light with laser-cooled ions trapped by rapidly-oscillating electric fields – are those in which the Nobel-winning research of Serge Haroche and David Wineland lies.

[Part 2, coming soon...]

The human machine: communication technologies

The previous post in this series can be found here.

Have you ever stopped to consider what makes you a single organism? It might sound strange, but it is a question dripping in biological significance. You may think of yourself as a neatly packaged single unit, yet you are probably also aware that this one unit is made up of tiny individual cells working together. But how do 75,000,000,000,000-odd cells cooperate with such precision? Why your cells work together is entirely separate question with answers to do with filling evolutionary niches and delegating functional roles; I'm talking about how they do it. That's the million dollar question! 

Well, to be precise, it's the $1.2 million (or 8 million Swedish Krona) question, as it was announced last week that this year's Nobel Prize in Chemistry (and the accompanying monetary reward) has been awarded to Robert Lefkowitz and Brian Kobilka for their outstanding work into the biology of G protein-coupled receptors (GPCRs). In this post I hope to give you an understanding of how GPCRs work, why they're important enough to deserve a Nobel Prize, and how they relate the question of how you stay as just one you.

GPCRs - the eyes and ears of the cell 

If you were a cell, how would you know what to do? When should you divide, where should you move, what should you make? You couldn't just do it randomly or to some pre-determined schedule because the human you're in is unpredictable and its cells must be flexible in their behaviour to match that. So, what you really need to make these decisions is information. This is exactly the same as how humans make decisions about our behaviour, we gather information about the surrounding environment through our senses and then act appropriately. A cell that receives no information from outside its own membrane is as impotent as a human with no sense of sight, smell, touch, taste or hearing. Ok, so they need information, how do they get it? As you've probably guessed given my snappy subtitle and general build-up, the answer is receptors!

Telling left from right: which side gets the heart?

The following is a guest post from fellow Collective Marvelling member Sedeer El-Showk. Sedeer blogs at Inspiring Science and can be found on Twitter @inspiringsci.

One out of every 8,000 humans is born with some of their internal organs on the wrong side of their body, a condition which can have serious medical consequences. Although we're usually described as symmetric, that's only superficially true. Like other vertebrates, we look symmetric from the outside but our internal organs show left-right asymmetry; unless you happen to be a Time Lord, you have only a single heart which is normally located on the left side of your chest.  Changes to the organization of the internal organs can lead to cardiac defects, misalignment of the bowel and other serious problems.  Many genes are known to play a role in establishing this asymmetry, but we still don't fully understand its evolutionary and developmental origins.  Earlier this year, a paper published in the journal PNAS described how this asymmetry is established by  subcellular components early in embryonic development.

Experiments with plants have already shown that subcellular structures can have an effect on macroscopic organs.  Cells are highly organized, dynamic, complex living things, more kin to a vast city than to a sack of fluid.  The cytoskeleton is an important part of this structure and plays a critical role in many processes, including determining the shape of the cell and acting as a transportation network, much like a road and rail network in a city. The cytoskeleton is a network of different kinds of filaments and microtubules, the roads and rails themselves, which in turn are built out of the proteins actin and tubulin.  A decade ago, scientists discovered that a mutation in one of these building blocks, tubulin, could have far-reaching effects in plants.  The mutated tubulin changes the shape of the cytoskeleton, twisting it; this changes the shape of the cells, which leads to flowers and other organs being twisted in turn.

Bovine endothelial cells with the nucleus stained blue and microtubles and actin filaments stained red and green, respectively. (Photo credit: Wikipedia)

Tubulins are a basic component of the machinery of life, found in every kind of cell.  Based on the belief that left-right asymmetry is a consequence of subcellular structures, a team of scientists led by Michael Levin at Tufts University in Massachusetts decided to investigate the role of tubulin in establishing this asymmetry.  They injected embryos of the frog Xenopus laevis with mutated forms of two tubulin related genes, Tubgcp2 and Tuba4, and followed the developing embryos to find out how frequently the internal organs were located on the wrong side of the body, a condition known as heterotaxia.  About one quarter of the injected embryos were heterotactic, with half of those showing abnormalities in at least two organs.  Amazingly, this was only true if the embryos were injected when they were still only a single cell; embryos that had already divided into two or four cells weren't affected by the mutated tubulin.  Whatever the mechanism involved may be, tubulin is clearly critical to a very early decision in the embryo which has long term effects on the positioning of internal organs.

The researchers weren't content to simply show that tubulin has a role in establishing internal asymmetry; they also wanted to explore how it might be accomplishing this.  One possibility is that changes to tubulin alter the structure of the microtubules which affects transport within the cell. The cytoskeleton is known to be biased towards the right half of the frog embryo, leading certain molecular motors and their cargo to be preferentially transported to that side.  This rightwards bias disappeared in the mutant embryos, supporting the idea that the mutated tubulin somehow disrupts the regular pattern of transport.  The researchers also used the mutant embryos as a tool to fish out a whole suite of maternal factors that depend on tubulin in order to be localized to one side of the embryo, including cytoskeletal and transport-related proteins which can form the basis of future research into how this asymmetry is maintained and propagated.

Finally, the team co-operated with scientists at the University of Illinois and Cincinnati Children's Hospital Research Foundation to verify that the same process takes place in other organisms.  They found that introducing mutations in tubulin led to changes in left-right asymmetry in both human cell cultures and the nematode Caenorhabditis elegans.  Since tubulin seems to play a  similar role in establishing asymmetry in frogs, nematodes and humans, the authors are confident in asserting that this is an ancient and conserved mechanism of left-right patterning.

In addition to its implications for an important class of human birth defects, this is a thrilling developmental story.  It's quite amazing to see how changes in subcellular components can propagate up through cells, tissues and organs to have an effect on the overall layout of the organism itself.  While the authors describe this as a mechanism which has been conserved during evolution, I think it may also be a common physical principle which different groups have taken advantage of.  Whatever its evolutionary origins, it's a mechanism which I find profoundly beautiful.  The idea that the orientation of the cytoskeleton is amplified by changes in subcellular transport to have major developmental and physiological consequences is so elegant that I can't help but revel in it.  This is the kind of story that makes me fall in love with science all over again.  The world may be fabulously rich and complex, but sometimes the explanation can be sublime in its simplicity.

Ref
Lobikin, M., Wang, G., Xu, J., Hsieh, Y., Chuang, C., Lemire, J., & Levin, M. (2012). Early, nonciliary role for microtubule proteins in left-right patterning is conserved across kingdoms Proceedings of the National Academy of Sciences, 109 (31), 12586-12591 DOI: 10.1073/pnas.1202659109

Curating for Scientists

 Image Credit: Malaghan Institute of Medical Research, Wellington, New Zealand

The picture is from Facebook: "The wonderful team at the Malaghan took some time out today to show Ruba and Rose (who generously donated their pocket money to the institute) around. Here Ruba looks at white blood cells through a very impressive microscope as sister Rose looks on."

My current role at a university art gallery should imply some kind of practical art and science cross over. After all, the scientists at the Malaghan - literally down the road from the gallery - are researchers with as much stake in the cultural life of the campus as the musicians, artists, film historians, and poets I talk to daily. Theoretically we understand this at the gallery. But we have to take a different approach to collaboration if we really want a more dynamic back and forth between the research we frame in the white cube and the research that is framed in the lab.

What is that approach? Did you visit the art gallery associated with the university you trained at, or work at now? Why not? What would it take to create that relationship?

The human machine: (thermo)dynamics of muscles

The previous post in this series can be found here.

The following is a guest post from Björn Malte Schäfer
(blog: cosmology question of the week, personal webpage)

How do muscles work?

Physics students learn the definition of work and mechanical energy in the first course on classical mechanics. Mechanical work is performed when a test body is moved against a force, and the work performed is equal to the (vectorial) product of the distance covered times the force, if it stays constant, otherwise you would have to evaluate an integral. If the test particle is stationary, no work is performed. But what what happens when you hold a heavy object with your arm? Even if you don't move the arm and don't perform any work from a physical point of view, it proves exhausting and after a while the arm starts aching. You at least have the feeling of having performed work, although this contradicts the physical definition of work.

Mechanical vs. molecular engines

What's wrong here? Are muscles different compared to engines? Clearly, there's a contradiction. It turns out that this example can be explained via the mechanism of molecular engines, which work very differently compared to the mechanical engines we're familiar with. And one needs to understand a bit of non-equilibrium thermodynamics!

Actin and myosin proteines

Muscles consist of two proteins called actin and myosin. Actin is in fact a very old "invention" of Nature, it is almost identical in yeast and in humans, and serves the purpose of cytokinesis, i.e. the separation of cells as well as locomotion. It consists of amino-acids and has a helical shape. Myosin is a protein that is able to change its shape under the influence of adenosin-triphosphate (ATP). It resembles a q-tip with a head that can carry out a nodding movement. The energy for changes to myosin's shape is provided by consuming an ATP molecule and dissociating it into adenosin-diphosphate (ADP). Fresh ATP is generated in mitochondria, which are small cellular organelles, by oxidation of sugars.

illustration of the actin-myosin protein assembly inside muscle cells

The actin-myosin engine

The actin-myosin engine proceeds by 5 steps: