The human machine: decommissioned components

The previous post in this series can be found here. 

Happy 2013 from all of us here in the Trenches! We successfully made it one more time around the sun, and if that's not a good excuse for a party I don't know what is! Sadly, however, not all of your cells have been having such a swimmingly good time since the calendar ticked over to January the first - in fact nearly one trillion of them have died in the past fortnight alone, at a rate of roughly 70 billion a day, or 800,000 per second. Don't be alarmed, however, as this has been going on for your whole life and is a vitally important part of being a multicellular organism such as yourself. A human without cell death would be like society without human death - overcrowded, unpleasant, and rife with infirmity. Your body needs a system by which damaged, old, or infected cells can be removed in a controlled manner; this process is known as apoptosis.

In this post I will be discussing what we know about how apoptosis works and how it is a key player in the development of cancer and the fighting of infectious disease. I'll also show how our understanding of how this process works has allowed us to devise targeted therapeutics against a number of debilitating conditions.

Cellular suicide - picking the moment

Your cells are team players - they're willing to do anything to serve you, including laying down their lives. Apoptosis depends on this loyalty because it is actually a form of suicide that your cells perform on themselves. Arguably the most important aspect of this is timing - if your cells are in the habit of committing suicide before it is necessary then you'll waste a lot of energy and resources building replacements that shouldn't be needed. On the other hand, if the cell leaves it too late to kill itself then it may find itself incapable of doing so.

So, how does a cell know when to die? Well the most obvious markers for cell death are simply the various forms of damage that can occur to the components of the cell itself. If a cell's membrane becomes damaged, for example, this can cause excess calcium to leak into the cell and so be sensed by a number of calcium-binding proteins, such as calpain, which in turn signal that apoptosis should begin. Similarly, damage to DNA is sensed by the complex machinery of the DNA repair pathway. For example, PARP is a protein that binds to single-strand breaks in DNA caused by DNA damaging agents such as radiation (think sunburn!) or chemical mutagens like free radicals. PARP and other DNA damage sensors relay their information to a number of signalling proteins, most importantly p53. If p53 is activated in response to DNA damage it signals to stop the usual processes of cell division and begin DNA repair, but if the damage is just too bad it makes the call to start apoptosis and destroy the cell.

A three dimensional fractal in 3D

The video below is a fractal. It is also three dimensional. It has also been rendered from two different locations very close to each other. Therefore, you can also see it in three dimensions.

If you're not used to using YouTube's 3d capabilities then don't worry, this guy has a tutorial video explaining how to see the full three-dimensionality of the video without the need for glasses. It's just like magic eye in reverse, basically (though I'm not sure how good it is for your eye muscles).

If you liked that you should read the description of how the Mandelbulb was discovered. The Mandelbulb was made by people looking for a three dimensional analogue of the well known Mandelbrot set. If you don't know what the Mandelbrot set is, first watch this video, then read about what you just saw at Wikipedia.

None of the Mandelbulb, or the Mandelbrot set or the 3d fractal (a Mandelbox) shown above were designed by a human mind. All of the complexity found in the images comes about from defining structures in two or three dimensional space as the set of points that are or are not solutions to relatively simple mathematical algorithms. For example, the algorithm describing the Mandelbrot set can be described in just one line:

"... the Mandelbrot set is the set of values of c in the complex plane for which the orbit of 0 under iteration of the complex quadratic polynomial \(z_{n+1} = z_n^2 + c\) remains bounded".

All of the complexity you can see in the entire ten minutes of the Mandelbrot set video I linked to above is defined in that one simple sentence.

Twitter: @just_shaun

Cinema verité - biology style

Animations of scientific principles are becoming more and more popular as a way of condensing complex data into an easily accessible format, particularly in the field of biology. Nonetheless, a recent article in Nature has raised a number of interesting points about how the visualisation of biological processes should not be taken lightly. Biology is unnervingly complex and there is still much that we don't understand - how are we to know how much of an animation is based on actual data and how much is just 'filling in the gaps'? This is not limited to the layperson - humans are very visual creatures and we are more easily swayed by pictures than words, experts are no exception. This is not new, journals have included idealised representations of biological processes for decades, but the advancement in computer animation has opened the door for more sophisticated animations that may imply a more thorough understanding where one does not exist. 

That said, I don't believe that researchers actively seek to mislead when presenting their findings in animated form, rather that they have to take the necessary steps to complete the movie - inherently requiring some artistic licence. And, for the most part, the bits being filled in are done so with reasonable scientific assumptions in mind and are not wild fantasy. The medium is an exciting one, and one that will hopefully play a significant role in not only disseminating scientific understanding, but also help to further research by highlighting gaps in our understanding. We must, however, always be vigilant when interpreting these animations as they are exactly that - animations - and not actual footage of molecular biology.

An excellent example of biological animation is the 'Inner Life of a Cell' video by a group in Harvard. I love this video, which depicts the events that occur upon the activation of T cell, and is pretty accurate in that almost everything show is backed up by real evidence. The 'motor protein' kinesin at 3:40 is particularly impressive because its mechanism of 'walking' along microtubules is backed up by extensive structural and biochemical studies, yet it just looks so much like a drunk guy who's been pulled over by the police and is trying to walk in a straight line! If you get the chance, I really recommend watching the video and reading the article mentioned above. Enjoy!

The human machine: circuits and wires

The previous post in this series can be found: here.

In the first post of this 'human machine' series, I explained how 'energy' (that abstract entity) is processed and used by our bodies in order to converted the chemical energy in our food into the work energy required to keep us ticking over nicely. I discussed in this how we are all actually powered by electrical circuits that buzz along in the internal membranes of our cell's power stations, the mitochondria. Better yet, not only are we powered by currents of electrons, familiar to us as standard electricity, but also by currents of protons, and so are actually working off energy being extracted from two forms of electrochemical potential. We're pretty sophisticated machines!

The work energy generated by these processes is used in myriad ways, but one very important one is the creation of another electrical current that is the foundation of everything you've ever done and every thought you've ever had: the neuronal action potential. This is the electrical signals that run along the neurons in your brain and body in general, constantly relaying information back and forth throughout the whole complex machine. Without it we would be like plants, with one part of our bodies completely unaware of what's happening to the rest of it, and animal life as it is familiar to us would be entirely impossible. Most people have, I expect, heard of the notion of electrical signals running throughout our bodies (it's why the machines built the Matrix, right?), but few will actually know what that means. In today's post I'm going to be talking about what neuronal signals actually are, and so explain why being hit by lightning is a bad thing but being defibrillated (like in ER) can be a good thing.

Open Sesame! - Diplomacy through science

For as long as I can remember being even remotely aware of international politics I have known one thing to be certain: Arabs and Israelis don't get on! It's a fact that I've grown up knowing and has been reinforced time and time again in recent years with seemingly unbreakable cycles of violence and ever more dangerous and confrontational political rhetoric from both sides. The most recent exchanges of ammunition between Gaza and Israeli cities is simply the latest chapter in this sad tale of a fractured region.

But how will the story end? Little diplomatic progress has been made in the resolution of the conflict in the 60 years that it has been raging, and indeed the conflict has spread to bring countries such as Iran and Pakistan into the front line of political warfare. The historic, cultural, and religious differences between the two sides seem simply too insurmountable to overcome, and so a bloody (and potentially radioactive) conclusion seems a terrifyingly possible outcome.

Yet, in the midst of all the hatred and mistrust, there is a glimmer of hope on the diplomatic front that has come in the form of a collaborative scientific project. Sesame, which stands for 'Synchrotron-light for Experimental Science and Applications in the Middle East', is a multi-million dollar particle accelerator currently under construction near Amman, Jordan. Synchrotrons are fantastically useful facilities capable of producing a form of light known as synchrotron radiation that can be harnessed to investigate materials on unbelievably tiny scales. One such application is the study of proteins and other biological molecules down to atomic scales such that their structure and function can be better understood, and potentially so that we can develop more sophisticated drugs to target them. I recently wrote about the 2012 Nobel Prize for Chemistry awarded to Robert Lefkowitz and Brian Kobilka, which would have been entirely impossible without facilities such as Sesame. 

Solar Eclipse

Southern Hemisphere view. This eclipse was only visible from New Zealand, Australia, and Chile.

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.