Designing drugs on the London Underground

When you think of drugs and the London Underground, you probably don’t get a completely wholesome, let alone scientific image. I am going to tell you how we can use systems such as the London Underground to improve the design of new drugs.

The London Underground map is an example of a mathematical network, or graph. This stems from the growing field of ‘graph theory’. It is made up of individual points, the stations, joined together by lines, the train tracks. But, we can copy this idea in biology. We can make a network like this, where the stations are individual proteins, and the train tracks between them are interactions between these proteins. This is known as systems biology.

But why would we want to do this? Traditionally, biology has looked at very specific things, like individual genes or proteins in great detail. But imagine you were to study a car, you wouldn’t just look at the engine or brakes in detail, you would look at how all of these components come together to make the whole vehicle. This is the approach we now need to take with biology, we need to start looking at the bigger picture. Building a biological network, like the London Underground, allows us to see this bigger picture.

Quite amazingly, when we do this, we see patterns arising. These patterns are present not only in molecular networks of proteins but also in networks of biological food webs or even social networks. Viewing these networks as a whole quickly allows us to see the key components (as these will have the most connections with other components), and which components are closely related, as they will interact with similar things, affecting similar cellular processes. This may not necessarily be obvious when only viewing the individual parts.

Credit: Eichelbaum et al., 2012, Nature Biotechnology

This picture shows an example of a biological network. Each circle represents a protein and the lines between them represent their interactions. It is clear to see that closely related proteins have more interactions between them and are grouped together. This allows biologists to see patterns and predict the functions of newly discovered proteins more easily, simply by looking at the other proteins it interacts with.

Now, and this is the exciting part, we can use these networks for the design of new drugs. Currently only 1 in 5000 drugs that enters pre-clinical testing actually makes it to market. Any drugs that fail cost the industry millions of pounds, usually failing because of unexpected side effects. Using systems biology, we can see from our network which components would make suitable drug targets and which would make poor targets, and, by looking at the interactions that exist, we can use it to predict any whole-system side effects of these drugs. This would not be possible by looking at the individual parts, and only becomes apparent when we view the effects on the system as a whole.

What’s more, using mathematical modelling, we can add experimental data to our network and turn it into a sort of ‘virtual cell’ on a computer. We can then use this virtual cell to make predictions about what would happen if we altered the network with various drugs, giving much more accurate predictions of which new potential drugs should be developed.

So by using systems biology, we can more accurately predict the positive and negative effects of a drug, before it has even been designed, before we have even been in the lab! This will lead to cheaper and more efficient drug design. But, this is only becomes possible when we can take a step back and view the bigger picture, something which we are finally starting to do.

FameLab UK Grand Final

I recently had the incredible experience of taking part in the FameLab UK Grand Final at the Bloomsbury Theatre in London. FameLab is a science communication competition that was started by the Cheltenham Science Festival in 2005. It has since grown into an international event, with 27 countries now taking part. Contestants have three minutes to present any aspect of science, technology, engineering or maths, the so-called ‘STEM’ subjects. The eclectic mix of humour, presentation styles and above all, interesting scientific topics, made the final an absolute joy to be involved in. Unfortunately, I was not successful in my bid to be crowned UK champion, but a huge congratulations to Emer Maguire for her incredible description of the science of love, which won over not just the judges, but the audience as well. Good luck to Emer is the upcoming international semi-final!

Here is the video of the 2015 FameLab UK Grand Final, I start at about 42 minutes for anyone who is interested, but all 10 are well worth watching. Enjoy!


Henrietta Lacks: Immortal yet forgotten

This is a story about a woman named Henrietta. Henrietta Lacks. Henrietta was born in Virginia in 1920. She grew up on a struggling tobacco farm, living in the same building where her great-grandparents had lived as slaves years earlier. In 1951 Just 4 months after giving birth to her fifth child, Henrietta was diagnosed with cervical cancer.

Meanwhile, scientists had been trying, and failing, for years to successfully grow human cells in the lab. This would allow scientists to study cells much more easily, to compare different cell types and even test the effects of new drugs. The problem was that normal cells will die a couple of weeks after you take them out of a human, so they needed a new approach.

Before we go any further, I just need to introduce cancer a little. Cancer cells are like cells 2.0. They are just much better than our normal cells at surviving. They are like those TV adverts you see for the royal marines: Run faster, fight harder, live longer… Be the best! They are the best. Therefore, scientists thought maybe there is a chance that these would grow in the lab.

One cell biologist named George Gey, decided to get his hands on as many cancer cells as possible and one of his patients was Henrietta Lacks. He cut a tiny sliver off her tumour sent it to the lab to be grown. He never asked for Henrietta’s consent to take her cells and he never checked with her family either. That wasn’t how they did things in the 1950s.

What happened next was simply amazing. Henrietta’s cells grew. And grew. And continued to grow. Nobody had ever seen anything like it. They were sent to labs all over the world. A factory was built to produce trillions of cells a day. Yet still Henrietta’s family knew nothing about them. The cancer killed Henrietta shortly after her cells were taken. She was 31.

Named HeLa, after the first 2 letters of her first and surnames, Henrietta Lacks’ cells are still growing today. They are present in almost every biology lab in the world, including mine. They have led to massive advances in cell biology, the understanding and treatment of cancer and the development of many drugs and vaccines, including the polio vaccine.

All of this research went on without The Lacks family knowing anything about it. It wasn’t until 22 years after her death that they were informed that Henrietta’s cells had been taken. Furthermore, they were only told because scientists came to take blood samples from Henrietta’s children under the implication that they were testing to see whether they were at risk of getting the same cancer that had killed their mother. In fact, they were searching for genetic markers, unique symbols in their DNA, which were specific for the Lacks family; in order to better understand the cells themselves. Parts of their DNA were sequenced without their knowledge and the results, their own personal private information, was published to the wider scientific community.

However, there is now some good news. With the advancement of DNA sequencing technology, Henrietta Lacks’ genome (all of her DNA) has now been sequenced. This has led to an unprecedented agreement between Henrietta’s family and the National Institutes of Health (NIH), which hopefully means that the case can be put to bed. The agreement states that only certain researchers can have access to Henrietta’s genetic sequence, and each application must be reviewed by a panel, which includes two members of the Lacks family. It only took 62 years for the family to get this recognition that they deserve.

In my opinion, the only remaining issue is that so few people have ever actually heard of Henrietta Lacks. Her cells have contributed a huge amount to biology and saved millions of lives, yet she is known worldwide by an acronym, HeLa, rather than by her actual name. Henrietta.

To learn more about this incredible scientific story, and in particular the family who lie at its centre, I highly recommend reading The Immortal Life Of Henrietta Lacks by Rebecca Skloot.


I performed this story as part of the FameLab UK ( regional heats. If you don’t want to read the story and would prefer to see me tell it, then watch the video below. Thanks!

Creeping and crawling: how cells move

My PhD is in the field of cell biology. More specifically, I am trying to find out how cells ‘feel’ and respond to the environment around them. I am on a one man mission to prove that they are not just boring blobs, but actually fascinating molecular machines!

One process that I work on is cell migration, that is, how cells move around. But why would a cell need to move around? I hear you cry. If you get a cut, your skin cells move together to close up the gap. If you get an infection or mosquito bite, your white blood cells leave the blood stream and migrate to the infected area, causing a red bump to form. Or in the developing foetus, where cells need to move to the correct location.  Cells that are going to become a liver need end up where a liver is meant to be. Problems with this can lead to some terrible diseases, for example, the rare but serious condition where cells that are destined to form the mouth and vocal chords migrate to and end up in the colon, something that I think has happened to Michael Gove.

So, clearly this is an important cellular process, but how does it actually happen. Well don’t migrate away and I’ll tell you. If I want to move from one location to another, I simply walk. But cells don’t have the luxury of legs. However, they do have tiny ‘hands’. These green streaks in the picture below are called focal adhesions. These are points at which lots of different proteins (acting like building blocks) come together and allow the cell to reach outside and hold on to its external surroundings. Through these, it is able to reach forward, grab on, and pull itself forward (using the red ‘rope-like’ fibres in the picture. These are called actin). It then lets go and pushes forward again. So it crawls along.

A cell with focal adhesions (green) and actin filaments (red). These work together to pull the cell along a surface.
A cell with focal adhesions (green) and actin filaments (red). These work together to pull the cell along a surface.

That’s it, that’s how cells move. But just think about that for a second. Each focal adhesion contains potentially thousands of proteins, which need to come together in a precise manner, pull, and then disassemble in a matter of seconds. That’s like doing a 1000 piece jigsaw puzzle in seconds, then pulling it apart and starting again. But there’s more, a cell could have tens or even hundreds of these adhesions, meaning you might have to do 100 1000 piece jigsaw puzzles in seconds, and keep repeating this.

This molecular complexity all contributes to a wonderfully simple process of a cell crawling on a surface, which I think really sums up the beauty of cell biology.

It is this complexity that we need to understand further. The most common and well-known cell migration disease is cancer. If cancer stays put it’s easy. A skilled surgeon can cut it out. Sorted. However, cancer cells are able to migrate much more than normal cells, and it is when the cancer spreads that it really starts to cause problems. So I don’t want to make any bold sweeping statements, but if we can increase our understanding of this process of cell migration, we could probably cure cancer!

An acid trip

I would like to say that I have a good excuse for not posting anything for so long; however, I would be kidding myself. New Year’s resolution therefore, more blog posts!

To start the year I am going to write about something everyone will have heard of, but may not know the details, pH. If your secondary school was anything like mine, you probably encountered this at around the second science lesson of year 7 (age 11/12). The previous week you had boiled water with a Bunsen burner, while, of course, maintaining safe practice and possibly even obtaining a ‘Bunsen burner licence’. At no point did you melt biros and burn the desk… me neither. This week’s (equally exciting) practical lesson involved dripping a greenish slime-coloured substance into various liquids and looking to see if there was a colour change. Of course, you were measuring their pH.

But what is pH? Most people will tell you it is a number from 1 to 14, with low numbers meaning acid, high numbers meaning alkali and 7 meaning neutral. However, what is an acid? What is an alkali? And what do these numbers actually mean? This isn’t properly addressed until A-level chemistry (6 years after that second science lesson). The correct (but complicated sounding) answer is that this number, the pH value, is the negative logarithm of the concentration of hydrogen ions in a solution. A statement that raises more questions than it answers.

A solution, by definition is a mixture of a solute dissolved in a solvent. For example, sea water is a solution of salt (solute) dissolved in water (solvent). It is common knowledge that the chemical formula of water is H2O, which means that two hydrogen atoms are bound to one oxygen atom. Every atom is made up of a nucleus (positively charged) surrounded by orbiting electrons (negatively charged). When hydrogen binds to oxygen (forming water), they share some of these negative electrons, which hold the atoms together. This is called a covalent bond.

However, in water, these bonds continually break and re-form, meaning water shifts between H2O and a mixture of separated H and OH. When this happens, the OH ‘steals’ an electron from hydrogen (H), meaning OH now has more negative charge and H becomes positively charged. Hence, they are written as H+ and OH. These charged molecules are called ions. H+ is the hydrogen ion referred to in the above definition of pH.

In a solution dissolved in water, the concentration of H+ multiplied by the concentration of OH ions is always equal to 10-14 moles/litre (1 mole = 6.02 x 1023 atoms). This is called the ionic product of water. Therefore, the concentration of H+ ions can range from 100 to 10-14 moles/litre. The pH of a solution is equal to the negative logarithm of this concentration of H+ ions. In water, the concentrations of H+ and OH ions are both equal to 10-7 moles/litre (10-7 x 10-7 = 10-14 moles/litre). Hence, the pH is equal to the negative logarithm of 10-7, which equals 7, or neutral. As the concentration of H+ ions increases, the pH drops. For example, a strong acid that has a H+ concentration of 10-1 moles/litre will have a pH of 1. Phew.

So that’s the theory, now what about the fun part. All of this leads to some very simple experiments that can be done at home, to re-create that sense of wonder that you had back in that early science lesson. Acids and alkalis are common place in the home, as are pH indicators; you just need to know where to look. Examples of household acids include vinegar (acetic acid) and lemon juice (citric acid). Household alkalis are substances such as bicarbonate of soda (used in baking – weak alkali) and bleach (strong alkali). Various indicators also exist around the house, the one I recommend using, simply because it is the easiest, is the Indian spice turmeric. Simply mix about a teaspoon of turmeric powder with a little water and add it to various acids and alkalis. At a neutral pH and below, turmeric solution remains yellow; however, at a pH of 8.6 or higher, it turns reddish brown. An alternative is to crush red cabbage with a strong alcohol solution (50% ethanol). The resulting liquid gives a much better range of colours over the entire pH scale than turmeric, but the requirement of using ethanol makes this harder to obtain.

Both of these substances work as indicators due to the pigments the give them their vivid colours. In turmeric, this is called curcumin, and in red cabbage it is a mixture of pigments, hence the broader range of colours. I really like these experiments as they use readily available, everyday items and give an immediate and obvious result. Furthermore, the theory behind the topic of pH demonstrates the complexities that lie within these seemingly simple colour changes.

Using turmeric as an indicator
Using turmeric as an indicator

Storm in a teacup

The British, as a people, are renowned for our non-confrontational and polite demeanour. That is until the topic of conversation moves on from the weather and, inevitably, becomes about tea. How should it be made? What material should the cup be made from? What temperature should the water be? Everyone has their own opinions regarding these questions for their ideal brew; however, one question that has broken friendships, ignited family disputes and generally divided our calm nation for decades is when the milk should be added, first or second?

Given the strong opinions that are held by the British on this topic, I imagine that several of you have just answered this in your head and are only reading on to see if I agree with you. God save me if I don’t.

There is a scientific explanation behind the best way to make tea. This states that the milk should be added first. Before you disagree angrily, please allow me to explain myself.

Originally a drink of the upper classes, tea became popular throughout Britain in the 18th century. However, those who couldn’t afford bone china cups and saucers had a problem. The poorly made, cheaper mugs couldn’t stand the heat of the boiling water, causing them to crack and break. The simple solution to this was to add milk, and to add it to the mug first, which would provide a barrier as well as cooling the boiling water, preventing the mugs from breaking. Hence, the phrase ‘a milk in first type of person’ rose to prominence,  describing the lower classes.

But, without realising it, the lower classes were on to something. Tea contains acidic molecules called tannins (see image below), which are also present in red wine. These molecules make the tea quite bitter. The proteins in the milk bind to the tannins, neutralising their bitter taste. If the milk is added to the hot water second, it breaks into smaller drops and the proteins in the milk are heated faster, causing them to become degraded (or, more scientifically, denatured). Subsequently, the denatured proteins cannot bind to the bitter tannins. This is avoided by adding the brewed tea (which will have now cooled) to the milk, leading to a smoother, creamier cup of tea. It also prevents to taste of ‘cooked’ milk from masking that of the tea.

Source - Wikipedia
Source – Wikipedia

The main argument against adding the milk first is that you can’t judge the exact amount needed, which is usually determined by the colour of the tea when milk is added. The author George Orwell was a famous supporter of the milk in second technique, for this exact reason. However, the science doesn’t lie, and for the perfect cup of tea the, milk should be added first.


Aerospace engineering, it’s not rocket science!

“It’s not rocket science, is it?!”

This now clichéd phrase, used to imply simplicity, has often annoyed me. There are two reasons for this, firstly, there isn’t really such a thing as rocket science; secondly, if there were such a thing, it would be relatively simple.

The subject often confused for rocket science is aerospace engineering, which is, to avoid insulting any engineers, an extremely complex and difficult subject. But engineering and science are two distinct disciplines. The main difference between the two fields was neatly described to me by an engineer-turned-biologist, who said:

“Scientists ask why, engineers ask how?”

A scientist uses scientific methodology to propose new theories; an engineer then uses these theories and applies them to a practical situation. Of course, there is a considerable amount of crossover in the subject matter, but the basic approach is where the difference lies.

Aerospace engineering was pioneered by Werner von Braun, who started out building rockets for the Nazis in WWII, before going on to work for NASA, designing the Saturn V launch vehicle, which was used to propel men to the Moon. It takes in to account everything required to build a functioning rocket, allowing it to be launched out of the Earth’s atmosphere, withstanding the harsh temperature and pressure changes, and still functioning correctly in outer space. It incorporates a huge number of areas of engineering, several of which have very complicated sounding names, like avionics and astrodynamics. Suffice to say, it takes a cleverer person than me to understand it.

So, what is rocket science? As far as I can tell, the only important ‘science’ involved in blasting a rocket into space is Newton’s third law of motion, which states that ‘every action has an equal and opposite reaction’.

That is to say, if an object applies a force to another object, the second object will apply the same force, back in the opposite direction. This is why, if you lean against a wall, it pushes back, supporting your weight.

Credit - NASA
Credit – NASA

So, if you fire up a dirty great engine and blast a huge amount of force downwards, the equal and opposite reaction will be to thrust the rocket upwards. If this force is great enough, the rocket will leave the atmosphere, boldly going where only a few men (and women) have gone before (not quite as catchy is it). The design of this engine and the amount of thrust required to push down, in order to lift the rocket are all questions of engineering, which is applying this scientific law to a practical situation.

So, when described as a science, this is a relatively simple concept. However, from an engineering point of view, it is extremely complex. Therefore, when someone says ‘it’s not rocket science, is it?!’ a perfectly valid response would be ‘it is that simple, but it certainly isn’t aerospace engineering!’ Unfortunately, this probably isn’t going to catch on.

I’ve got U(V) under my skin

The burning red sunburn fades into a ‘healthy’ brown. The pain has subsided and, in the knowledge that your complexion will spark jealousy in your co-workers upon your return, it all seems like it was worth it. But was it?

To follow-up my previous post about how sun cream protects your skin from the Sun’s powerful ultraviolet radiation, I thought I should write one to explain why exactly it is important to use it and the dangerous, cancer-y consequences of prolonged sun exposure. Just to be clear, I am not trying to preach (and, country to popular belief, I don’t work for a sun cream company), I am simply trying to inform you of the fascinating (and potentially deadly) science that takes in your body, in response to UV radiation from the Sun.

So first of all, what is cancer? Cancer is simply your own cells, but they are growing too quickly, forming a tumour. Due to the speed at which they grow, they starve the nearby healthy cells, eventually killing them. Depending on where this happens it can, clearly, be very dangerous.

Most of the cells in your body need to grow and divide all of the time. Damaged or dead cells are continually lost and replaced by new, shiny counterparts, and life goes on. There are two types of genes that control the rate at which cells divide, which can be thought of as the accelerators (the oncogenes – onco basically means cancer) and the brakes (the tumour-suppressor genes). Genes are made of DNA, which is a code of 4 letters, A, T, C and G (see here for a quick review). If any of the letters that make up this code are changed, the gene is said to be mutated, and this can have drastic effects on its function. If an accelerator becomes over-active, and the brakes stop working, the cells begin to divide out of control, and cancer is born.

UV light targets DNA. Specifically it targets the bases T and C, which are known as the pyrimidines. The energy in a beam of UV radiation causes 2 neighbouring Ts and/or Cs to stick together, forming a ‘pyrimidine dimer’. This can no longer fit into the neat, compact double-helix and when the DNA is replicated, these two bases are missed out. The code has therefore changed, it has been mutated. If this mutation occurs within one of the accelerators or breaks, it can change their activity and potentially cause the cells to grow uncontrollably.

The formation of pyrimidine dimers
The formation of pyrimidine dimers

Humans have approximately 20000 genes, so the odds of this happening to a specific gene AND the mutation having the required, cancer-causing effect, are clearly very low. The cell is also able to repair most of these mutations, giving us a slightly better chance in the war against ultraviolet. However, the longer the skin is unprotected and exposed to UV light, the more and more likely this becomes.

This said, don’t be afraid of the Sun! You do also need sunlight to remain healthy, and not just in the sense of avoiding being a recluse who lives in the basement, afraid of natural light. This, I do not recommend. Your skin needs to be exposed to some UV light as it is vital for producing vitamin D, which is important for the maintenance of healthy bones. However, the amount of UV radiation required to produce an adequate, bone building supply of vitamin D is much smaller than the amount that causes sunburn.

It is about finding a balance. You need sun exposure for vitamin D production, general happiness and, obviously, that envy-inspiring tan. But, by triggering the formation of pyrimidine dimers, which are subsequently deleted from the DNA sequence, it is able mutate the DNA. When this happens enough times, a tumour-suppressor or oncogene will eventually be affected, leading to uncontrolled growth of the skin cells.

As I said, I am not trying to convince/force you to use sun cream, all I care about is that you know what is happening under your skin, and hopefully find it interesting.

U v. The Sun

Summer is upon us. Or, if you are British, it may already have passed. During the past few weeks of glorious, if unexpected, sunshine in the UK and Europe, sales of sun cream (or sun screen for the Americans) have soared.

But how does sun cream protect your skin from the Sun’s unrelenting rays? How can this unassuming cream provide a barrier against such a powerful adversary? These are clearly burning questions.

In his famous double-slit experiment, the physicist Thomas Young proved that light has the properties of a wave. The standard measurement used to describe the properties of a wave is the wavelength, that is, the distance between two matching points, such as peaks or troughs, as shown in the picture. Visible light has a wavelength of 400-700 nanometers (1 nanometer (nm) = one billionth of a meter), and at a slightly lower wavelength, ultraviolet (UV) light has a wavelength of 10-400 nm, both of which are emitted by our Sun. The vast majority of the emitted UV energy (>97%) is absorbed by the ozone layer, the protective part of our atmosphere, without which, we would be cooked. The UV energy that is able to seep through the ozone layer is split into 2 categories, UV-A (320-400 nm) and UV-B (290-320 nm). It is the latter of these, UV-B, which is responsible for tanning and eventual sunburn. UV-A, on the other hand, is able to pierce deeper into the skin, causing the skin to age and wrinkle, eventually leading to cancer. On an interesting side-note, UV-B cannot travel through glass, hence you cannot burn through a window; however, UV-A waves can, so can still cause damage when you are inside.

In order to avoid sunburn, a barrier needs to be formed between your skin and the damaging UV rays. Sun cream employs two groups of molecules to do this, some that reflect UV rays, and some that absorb them, both of which prevent them from reaching the skin.

Zinc oxide and titanium dioxide are the two most common substances used to reflect UV rays. Their ability to reflect both UV and visible light is the reason why people wearing higher factor sun cream appear to ‘glow’ more in flash photography. White zinc oxide cream also is a common feature with surfers and cricketers (mainly as a distinctive fashion statement), and can be seen adorning the lips of some of the England players, while they are busy retaining the Ashes this summer!

Several complicated sounding molecules are used to absorb the UV rays such as para-aminobenzoic acid, Cinnamates, and Benzophenones. The common features of these are the presence of a ring of 6 carbon atoms, called benzene, and also several carbon-carbon double bonds. Most importantly, both benzene and carbon-carbon double bonds have a pool of shared electrons. These float around between the atoms and it is the sharing of these electrons that forms the strong bond between them. It is this pool of shared electrons that is able to absorb the UV energy, and release it as heat, meaning that it doesn’t reach your skin.

Benzene (left) and carbon-carbon double bond (right) absorb UV radiation
Benzene (left) and carbon-carbon double bond (right) absorb UV radiation

One final important point is that the sun protection factor (spf) on sun cream only relates to the protection provided against UV-B rays, as this is what causes sun burn. It is important to use a sun cream that gives a broad range of protection, against both UV-A and UV-B.

So it is the combined effect of molecules that both reflect and absorb UV radiation that allows sun cream to act so effectively. As it is such a ubiquitous commodity, the fascinating science behind sun cream is largely ignored. Its ability to protect us so effectively from the dangerous UV radiation of the Sun, coupled with its ease of application and almost non-existent side effects, makes it, in my opinion, one of the best inventions around today… although this may be just because I am pale and pasty.