The walking viral-microbial-fungal dead

I've just finished watching the first season of "The Walking Dead", yes I know, where have I been, there are already 4 seasons so hey no spoilers everyone. But what a series it is! Exciting stuff and I can't wait to spend another 12 hours today getting through the 2nd season.

The zombies will be amongst us once more for this year's Halloween. Tonight will bring the rise of pasty white faces, fake blood and calls for "braaaaains". Thankfully, not the actual flesh eating, party spoiling type but more the we like to get our drunk on kind. But what is it that makes those guys on The Walking Dead so antisocial?

The last two episodes of the first season gave us a big insight into the science behind the zombification that has plagued the world. The team end up at the Centre for Disease Control (CDC) where Dr Jenner is the last scientist standing. He seems to have a pretty neat set-up with voice activated computers and a top notch lab. So good is his equipment that through a standard bench top microscope he can see DNA. Yes DNA, that stuff in everyone's cells that is only a few billionths of a millimetre thick. Wow, I only wish I had access to that kind of kit. He later shows the other guys a video of Test Subject 19, with the "MRI virtual camera" and we see the brain activity dying out and coming back before he shoots a bullet through the patient's head. He fired a gun in an MRI machine! That could not have done the equipment much good, no wonder they hadn't made much progress.

Despite the cutting edge work that was obviously possible at the CDC, Dr Jenner admitted that they didn't really know anything. "It could microbial, viral, parasitic, fungal ... or the wrath of god!" Well, from the earlier microscope view I'd put my money on viral. Other (real) viral diseases like HIV and influenza are so difficult to treat due to the complicated nature of how they attack cells and mutations constantly altering them. Viruses are of course not treatable with common antibiotics and without proper hospitals available the infection will no doubt kill you fairly quickly. Luckily for us, in a "real" zombie attack, all that rotting flesh would fall prey to Nature's excellent ability to clean up the dead.

These scenes really made me laugh out loud. A nice attempt by the show to bring some actual science to it that was maybe lacking but maybe not needed. Always fun to see them try though and can only be a good thing for making people aware of current (more likely far in the future) technology and that in an apocalypse science is still very important. Also if you want to do research whilst the world is ending, then go to France, apparently those guys can last the longest.

The PhD that was

After having submitted my thesis last week, I thought it time to retire the PhD page from my blog. So here it is for posterity...

I had the pleasure of working with Dr Bruce Turnbull at Leeds. My project was to develop general strategies towards controlling protein self-assembly into designed nanostructures.

Taking advantage of weak protein-carbohydrate interactions we aim to construct three-dimensional nanoscale virus-like particles and other nanoarchitecture (my new favourite word). Ligands of various lengths, and with different carbohydrate moieties of varying affinity, have been covalently attached to the cholera toxin B‑pentamer (CTB). The carbohydrate units bind into the natural binding pocket of another CTB pentamer, bringing the proteins together to form different aggregates and particles. Analysis of the structures can be performed with AUC, MS, AFM, SEC, ITC, DLS and any other acronym you can think of.

So what does it all mean?

Well, to simplify things just imagine a brick. Now stick some velcro to that brick. Then get a load of these in a bag, shake them about a bit and hopefully out should pop a discrete spherical object. If this sounds unlikely and a bit crazy then you've grasped the idea perfectly.

If we can build organised, controlled structures on the nanoscale then this opens up possibilities for nanomachines, templated reactions and drug delivery vehicles.

PhD life

Doing a PhD is stressful, hard work and immensely fun. The work differs day to day with massive highs when your reactions unexpectedly work and terrible lows when your proteins commit suicide. There is a lot of self-motivation and commitment needed to complete a successful PhD, and it also helps having a great team around you and a kind word of encouragement every now and then (cheers Bruce). All for the advancement of the human race, and maybe also for the title of Dr before your name.

 

Dalí makes it into Nature Chemical Biology

Wow, just wow. Nature Chemical Biology has done it. Yes they have published the most bizarre and surreal image ever to be unleashed on a journal front cover.

Dream caused by neuronal decay

Salvador Dalí could never have imagined that one day his work would feature in such a prominent place for an artist of his stature. He could not have thought this in his wildest dreams, and he did have some pretty wild dreams. The image takes inspiration from 3 of his famous paintings, the first being "Dream caused by the flight of a bee around a pomegranate a second before awakening". Well, there are no pomegranates here but we do have a tiger leaping out of the sky and clamping its jaw around a neuron. Pretty cool and not quite as confusing as the pomegranate, fish, tiger, tiger, gun sequence from the original painting. The melting clock in the foreground is of course from Dalí's "The persistence of memory", its presence here probably a sad reflection that Huntington's disease can affect many people early in their lives. And finally the trees in the background come from "The three sphinxes of bikini". They are meant to symbolise the mushroom cloud of an atomic bomb in the original painting and so here gives another hint to the deadly nature of the disease. Not really much fun here after all.

I like that Nature Chem Bio does give you a little peak into what the authors were smoking when they made the image. The tiger apparently is meant to show the "difference in proteostasis mechanisms" which determines the "longevity of a neuron". Hence why our tiger is trying to eat that giant neuron.

No tigers were harmed during the making of this cover

The Paper: Proteostasis of polyglutamine varies among neurons and predicts neurodegeneration
Found at: Nature Chemical Biology, 2013, 9, 586-592

The paper is a study on the huntingtin toxin, a protein that causes Huntington's disease. The level of glutamine residues in the toxin can vary and it is this variation that leads to the protein misfolding and causing the disease. The larger polyglutamine regions were important as they also reduced the lifetime of the toxin. It was found that different neurons cleared the huntingtin toxin at different rates, with cortical neurons acting quicker than striatal neurons and thus living longer. They concluded that the biological pathways and in particular the Nrf2 pathway, responsible for protein degradation would be good targets for therapeutics for treating misfolded protein diseases. So maybe some good news in the end.

Geek week communication

It is geek week on Youtube and so I thought as science falls firmly into this category I'd highlight a few short videos I'd class as great science communication. They are all quite different and show the variety of things possible in front of a camera. I wrote a post not long ago about how words are important for communication, but of course that is not the only medium available for telling your story. Videos can be a great source of information and far more appealing in some cases. 

The complex life of sugars

This film was made for the Royal Society Summer Science exhibition that took place in London earlier in July. It's a nice whizz through all the areas of normal life where carbohydrates are found. The graphics are amazing, it keeps things very simple from tree bark to microarrays. Importantly also, the chemical structures are accurately shown which is unfortunately not always the case in popular science.

Conference call

The second film is a discussion of what is synthetic biology and where is it going. The film was produced at a conference of the Synthetic Components Network and nicely combines interviews, discussions and fancy images of proteins. Make sure you pay attention at 1.30 for a cameo appearance from yours truly. As a finger is pointed towards my poster, Beth Bromley says, "...they have no idea of what's impossible". Thanks Beth.

An extreme sport

The third video here might have been just a bit of fun, but it is really fantastic and a great example of how anyone with a camera can make an exciting and engaging short film (about chemistry!). I bet you've never seen a camera on a rotavap before...

For more great science videos have a look at Kyle Hill's round up for Scientific American and of course for all the ladies out there I couldn't write this post without mentioning the amazing awful "science: it's a girl thing".

Conference tweeting

At the recent International Symposium on Macrocyclic and Supramolecular Chemistry conference (ISMSC8) there was a distinct lack of interactions through social media.

Whilst coffee breaks and poster sessions were full of interesting chats and discussions, the internet was almost completely ignored by the attendees. The ISMSC website encouraged the use of the hashtag #ISMSC before the conference began. But in the book of abstracts and throughout the conference there was no mention at all of Twitter, I was disappointed.

There were a couple tweets in the build up before the conference, giving hope of a social (media) bunch of people.

On my way to #ismsc ! I will present the last development of the peptide synthesising molecular machine. See you there.
— Guillaume De Bo (@GuillaumeDebo) July 6, 2013

But during the conference I found myself a little lonely with only Ivan Aprahamian and Guillaume De Bo really contributing. Ivan summed up the twitter experience calling the crowd "technologically challenged".

300+ plus chemists at #ismsc and only ~10 tweets
— Ivan Aprahamian (@aprahamian) July 10, 2013

With sponsorship from Nature Chemistry and the National Science Foundation, both pretty big in Twitterland, you might have expected some input from them. But alas no, it was left to Chem Comm to join us at the end to publicise the poster prize they were sponsoring.

Big congratulations to Brandon Hirsch (Indiana) winner of @ChemCommun grand poster prize - he won a future front cover of ChemComm! #ISMSC
— ChemComm (@ChemCommun) July 11, 2013

Another chemistry conference, ISACS11 is taking place this week with around 50 tweets just from yesterday, although mostly dominated by one Chemistry World journalist. Whilst this is not a huge amount it is still much better than at ISMSC8. Derek Lowe is also present and so he's busy blogging through some of the talks.

But what is going on here? Is it just a generation difference and the young folks need to step up or are some conferences missing a trick? Get the discussions going over some coffee sure, but continue it and spread it further on the internet.

My first conference talk

The chemistry postgraduate conference was at Leeds last week and I gave my first ever proper conference talk. Being in the last couple months of my PhD and therefore extra busy, extra stressed and with no time for distractions like these silly presentations, I left things to the last minute.

So it was only an internal meeting and the audience mostly made up of other postgrads from the organic section, but speaking to a full room is never an easy task.

The build up

A hash together of group meeting slides and figures from previous reports gave me something to practice in front of the lab group, with 3 days to go. I tend to think I am quite good at winging it and this is generally my theory for life, but in this case it wasn't great. I realised this was kind of a big deal and therefore I should put a bit of effort in. Therefore next couple days were spent creating ChemDraw schemes, making cartoon figures and in 3 hour meetings with my supervisor.

Athene Donald wrote a great blog post about the pitfalls of conference presentations, with the key point being practice, practice, practice! I can only agree with her. I also got a handy tip from my supervisor to make sure it started well. he suggested that I learnt a script for the first couple slides of introduction so that I knew exactly what to say at the beginning and wouldn't stumble through incomprehensible mumbles.

Amazingly, it all went rather well. I knew what I wanted to say and said it. I spoke confidently and even managed to get a couple small laughs in, thankfully no tumbleweed moments. I handled some probing questions, avoiding anything too deep on the synthesis or too general on the reasons (applications are overrated). Shown above is one of my slides giving the (one day) infamous cartoon depiction of the cholera toxin protein, everyone knows that it's red right? In our lab, every protein has its own colour.

And relax

My talk was the last one of the day, a potentially awful slot if everyone is fed up by then and itching to get to the wine reception. But it was nice afterwards to not have to sit through any more pretending to listen whilst going over my notes. I had some great feedback from friends and academics and then got in to the bitching about some of the other talks.

Blue background and then blue data points on a graph, bad idea. Switching to a second presentation because you left out or forgot to talk about something, bad idea. Talking in a voice so deep you make the floor vibrate, bad idea (maybe I'm just jealous about not having a deep manly voice for this point).

I now know what to expect next time around and what to do better. I'll always remember this as a first effort and maybe with some feeling of nostalgia. The conference was followed by a ball in the evening that was also a memorable event, or not so for those of us overindulging in the free wine.

What am I on about?

Seriously, what on earth am I going on about?

When trying to get your point across, have a debate or tell a story it is very important to say the right words. Communication is all about language and used well can be an incredibly powerful tool.

First some common words

I wanted to have a look at the language I've been using on this blog and see if I'm saying the right things or in fact (more likely) saying some very strange things. I thought that a quick trip over to Wordle, a nice website for making fancy word displays, could tell me what I wanted to know. The 75 most frequently used words from my last 10 blog posts are displayed below.

The most obvious and bizarre thing is that I apparently say first an awful lot! I say first more than any other word. Why? I don't see second in the wordle. Maybe I don't think second is important. Maybe I get so distracted with the first thing that I ramble on and then start talking about other questions like oh look questions is pretty big on the picture too.

Science is up there, journal, work, cover (I do talk about covers a lot) but there are other surprising big ones such as one. When do I say one? Am I talking about unique occurrences or again get bored after the first? I'd like to see more superlatives being used. Great is there, but I have much better words than that in my vocabulary. I think science is wonderful and we should use equally wonderful words to describe the amazing world we live in.

There's no point doing ground breaking work and not telling anyone about it and that's where words come in. Language can not only be useful but also fun. Playing around with your split infinitives can allow you to boldly go where no scientist has gone before.

Birthday celebrations

This week is my birthday. Woohoo! I'm now into my late 20s, one step closer to death...

Birthday covers

To celebrate my constant loss of brain cells and the failure of my DNA to replicate properly, I thought I'd have a look at another big birthday that happened this year. My favourite journal, Angewandte Chemie, celebrated 125 years of publication.

To celebrate the occasion a gathering of the great and the good was held in Berlin earlier this year. Backs were patted and many nice things were said, including a piece from Stuart Cantrill with some interesting trivia. The journal started as a magazine for industrial chemists published in German, the journal title itself translating as 'applied chemistry'. English readers had to wait until 1962. The journal has actually been going for 126 years but had a year off in 1946 due to the war. So with 125 years of published articles, the covers in January were fittingly congratulatory; fireworks and champagne all round. The Issue: Angew. Chem. Int. Ed. 2013, 52, 1-466  (notably open access).

The original cover

There really is a lot to celebrate for the guys at Angewandte. They've been at the forefront of the evolution of journals over the past 50 years especially. They were the first chemistry journal to introduce graphical abstracts and also the first journal to have pictures on the covers. Before this there was simply a list of featured articles and other journals at the time just started straight off with a table of contents.

The January issue in 1977 was a breakthrough. Scientists now had a platform to paint a picture worth a thousand words. Ok, they weren't as flamboyant as the fireworks quite yet, but a massive leap it must have been.

The paper: Experimental Electron Densities and Chemical Bonding
Found at: Angew. Chem. Int. Ed. Engl. 16, 32-40, 1977

Taking a look at that first cover, all I can say is, wow! What on earth is going on there? To start with, it's in black and white (colour wasn't invented until 1986). A pretty simple picture compared with today's outings but pretty intriguing for a first attempt. There are some contours which suggests an energy landscape with peaks between the, presumably, atoms of C, C and N.

The paper is all about electron densities and quite frankly is way out of my field. But I was right with the contour map, so go me! Taken out of the paper the caption for the image states, "Deformation density in the plane of the three-membered ring of 2,3:5,6-bisepimino-p-benzoquinone at 143 K." Well that certainly clears everything up.

As we've seen, things have moved along significantly. There have also been a few surprises along the way, a humorous cover from 1987 used cartoon acrobats to demonstrate radical chemistry. Perhaps Angewandte should also be congratulated as the original place for TOC ROFL.

Chemical poetry

This week on Twitter has been all about Real Time Chem, if you've somehow missed it then you are spending too much time in the lab.

 

Real Time Chem is a great community project on Twitter using the hashtag #RealTimeChem. Chemists all over the world have been sharing their daily experiences, lab work, cool articles and finding solace in the fact that they are not the only one failing to purify that unknown black mess.

Amongst other things this week, I have been doing some isothermal titration calorimetry (ITC). A wonderful technique (when it works) of measuring the binding enthalpies and association constants for non-covalent interactions. It's one of my favourite pieces of kit to use; it can give great insight into the success (or failure) of synthesised ligands and makes some pretty graphs.

 
After setting the experiment going I had about 30 minutes to procrastinate before the run was finished. So the internet gets fired up and through a strange connection of aimless link clicking, on websites including "Facebook", "Chemistry World" and "Jet2 cheap flights" (possibly not in that order), I came across Nobel prize winner Roald Hoffmann. Whilst obviously being a great scientist, Professor Hoffmann is also the author of a large number of poems. Some of his work focuses on chemistry and I thought what a fantastic medium poetry is for expressing the wonder and excitement of uncovering nature. I'm sure it would work equally well for portraying the torment and anguish at failed reactions, but let's stick to the wonder for now.

Back at the ITC, a flash of inspiration hit me and I came up with a poem all about the technique...


Isothermal Titration Calorimetry

Separate they contemplate their lives alone
But this the only thought they share
Not knowing their worlds are about to collide
Never loneliness will they again bear

One passively waits for an injection of life
Floating in their own little cell
The other poised to mix at the first chance
That stirring sensation will tell

But it takes another to set their paths
One who knows what makes them attract
To turn up the temperature, wait for the calm
Push the right buttons, see them interact

An initial touch, not sure where it will lead
At first you can never quite know
But a second feel, a larger reach
The heat given off starts to show

As if they had always been as one
They're together and will never part
The creator watches his successful work
Plotting their lives as a chart

Their story lives on for others to see
An example for anyone that looks
To find a guest for that elusive host
Written down in the wisest of books

Imaginary elements

It's time to sit back and relax. Put your feet up and put on a good film... oh here comes some actual chemistry, a surprising rarity in sci-fi. Oh and it's totally inaccurate, excellent. 

#ChemMovieCarnival

As part of the "chemistry at the movies" blog carnival hosted by @SeeArrOh I'm going to look at a film that split viewers into lovers and haters. Avatar. An epic sci-fi and a basic remake of every other struggle of good vs evil, but with a huge budget and in 3D. So obviously, I thought it was awesome.

The film's premise is based on chemistry. Well at least it is based on the hunt for a new resource, a new mineral, a new element, whatever it is they give it an interesting name; unobtanium. Since Mendeleev put together the world's most famous piece of furniture, chemists have been working to fill in the gaps and add on to the end. So where does unobtanium fit on our nice little table?

Well it doesn't really fit anywhere, it's not real. But being not a real element is not a problem. The fictional element dilithium in Star Trek and the alloy carbonite in Star Wars have both become cult favourites and their use in the films is totally acceptable. The only problem that I have with the fictional unobtanium, is its name. The people at the Resources Development Administration must have used up all the hardtofindium and long ago depleted their stocks of wishwehadmoreofthisium. They had to get their hands on a new super element. James Cameron in his wisdom came up with a totally implausible name that no sane scientist would give to such a sought after material. It's this stupid name that in my opinion lets down an otherwise flawless film...

(What? There are body swapping giant blue aliens and floating mountains? That's totally fine.)

Other appearances

Unobtanium has actually made it to the movies before. In The Core, it was used to build their ship. A scientist in the film gives us a small insight into its composition, he "combined the chemicals in a tungsten titanium matrix", hmm.

The name has also been in use by engineers since the 1950s, according to trusty Wikipedia. So these films really could have put in a bit more effort to come up with something that sounded more sciencey. The tradition now is to name it after the discoverer or institute or a famous scientist, so what was wrong with Pandorium or (an egotistical and possibly worse) Cameronium. Despite being completely silly, unobtanium can still take its rightful place on the periodic table of imaginary elements (I have this poster on my wall), with other beauties such as dalekanium and crapcrapium.

For more Chem Movie Carnival fun follow the hashtag or have a look at this summary. I'd highly recommend the synthesis of kryptonite and how to poison a nitrogen based life form.

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