Monday, 7 July 2014

The making of a cover

I'm on the cover! One of my scientific ambitions has just been fulfilled.

From the moment I began my PhD I had but one aim... finish the PhD. Well I managed that last year, but I also had other ambitions for my scientific career and one of them was to have my work featured on a journal cover. The first time I dived into the scientific literature and saw these cover designs, I knew straight away that I had found my calling in life. Ok, so this is a slight exaggeration, but I do think they are really cool.

Authors use all sorts of ways to demonstrate their work visually. But obviously some fields of research lend themselves more easily to the use of pretty pictures than others. My work with protein interactions was certainly one of these areas.

The first sketch

It was in July last year that I had a break through. My proteins were binding in the way that I wanted and things were finally all coming together. As a quick summary, the work involved attaching 5 carbohydrates to a non-toxic mutant of the cholera toxin protein. That modified protein could then be used as an inhibitor of matching size to the original toxin. The carbohydrates of the inhibitor bind to the wild-type cholera toxin, therefore inhibiting the wild-type from sticking to your cells.

I was sat in the back of a seminar a week or so after getting my latest results, when my thoughts wandered onto how I could visualise the work. In my mind there was only one way to show the interactions and that was by anthropomorphising the proteins. I sketched down a first rough cartoon. The noble inhibitor was obviously going to try to catch the evil toxin. I don't remember much of the seminar, but I think this was still time well spent.

original sketchThe modified protein, our hero, had 5 large arms to catch the bad guy, oh and a police badge giving him the authority to hunt down these no-good toxins. As for his nemesis, well this guy had to wear the stereotypical black stripes and face mask of a robber as well as holding onto a swag bag to keep all his loot. As if this did not yet make it completely clear that he was not to be trusted, he also has evil eyebrows, a sure sign of a villain.

My initial sketch was not complete fantasy. The 5 arms represented the addition of carbohydrates to the protein. The swag bag represented for the toxic subunit that the wild-type protein possesses. The big googly eyes represented, oh no wait, they were just big googly eyes.

Writing the paper for this work was put on a list of things to do for quite a while and with it went the protein policeman. I was away at international conferences (holidays), I then had my thesis to write and after that a change of country. So it wasn't until February that the first draft of the paper appeared and as with any publication, a TOC (table of contents) image was needed. Here, the protein enemies resurfaced.

From notebook to TOC

First TOC image
The cholera toxin protein is fairly well known, with many crystal structures. Therefore, it was quite an easy task to scan through the protein data bank and pick out a nice structure as a starting point. A ribbon representation of the protein structure was chosen to start with as I believe this is the most recognisable protein depiction. Using Pymol, I then built in the alkane chains and added the carbohydrates around the protein. There was no choice for the colours, there is a standard scheme in the Turnbull lab; red = cholera toxin, orange = non-toxic mutant. The proteins were structurally accurate, the eyes and mouths were added for effect.

The initial design got the thumbs up from the lab group although it certainly needed a little refining. So after trying a few different positions and angles, the protein ribbon was changed in favour of a surface representation and a decent image was taking shape. The mask was added back in for the villain. A whistle and a police badge were given to our hero. Not the most serious piece of work, but we were confident that the actual research was good enough so that we could relax a little with a silly image.

From TOC to cover

I really wanted to try for a journal cover. We had some great work (I thought) and a great idea to build the TOC image into a full picture. The paper had been submitted to Angewandte and so the image had to be based on their standard circular design.

Final Cover!We went through 15 versions of bacteria for a background. Red, yellow and blue bacteria, some more realistic than others. I also tried out a Petri dish with bacteria growing across the plate but a consensus was made for an image with some large green bugs. The proteins stood out in the foreground and the colours worked well. Bacteria was used because the work is about protein modification and binding, and of course we couldn't perform any of the work (or have need to) without some little E. coli factories churning out all that protein.

A final change was to put some actual science into the image. Straight through the middle, separating the two enemies is a curve from one of the ELLA (enzyme-linked lectin assay) experiments reported in the paper. It gives the inhibitory potential of our good guy binding to the baddie. A fitting central divide.

All the best pictures have something a little bit ambiguous about them and here I feel that confusion is provided subtly by the police badge. The acronym refers to the top detective agency at Leeds University. CTPD, of course, standing for the Cholera Toxin Police Department. At this institution they only hire the most specialised proteins to catch the toxins.

The paper was accepted with great reviews and even recommended as a VIP paper. Excellent news! After much celebration we submitted the cover design. The editors were very quick to respond and accepted our image. More excellent news! I was amazed by how incredibly smoothly everything had gone. For my first first-author research paper this was fantastic.

I'm not sure if the image is quite bad enough to make it into TOCROFL, that will be the aim for my next paper. And after that my next scientific ambition is to get an SI unit named after myself, so we'll see how that works out.

You can find the paper "here" and our awesome cover design "here".


  1. This post was inspired by Sylvain Deville's post "The making of a paper", a great read check it out.