Life of a Lab Rat

"My, what big exons you've got. Do you want to see my spliceosome?"

"Hey baby. . . let's go clone some inserts"

Here's a fantastic Christmas present:

The Journal of Cell Science is making its entire scanned archive freely available online. One hundred and fifty years of cell biology.

Lots of holiday reading there. Some interesting factoids in Fiona's editorial, too:

One eminent director of The Company of Biologists suggested we should simply call the new incarnation Cell – rightly, this was deemed an inappropriate title for a serious academic journal.

Har har — it's a laugh a minute in this business.

Over at the Forum (well, a forum, anyways), a denizen complains that the Press does not identify the 'scientist' in headlines of the sort "Moon cheese makes your toenails grow, say scientists". This is, our complainant complains (um, sorry about that) in contrast to the treatment of 'celebrities' by the media; "The actor Russell Crowe told reporters that", and that this difference serves to reinforce the gulf that exists between media attitudes towards entertainers and scientists.

Check the BBC news pages and you'll notice that they nearly always start their science news stories with the word 'scientists' appearing as the subject (e.g. Scientists have discovered that...'. Contrast this with their approach to entertainers, who will usually be named as the subject, and their discipline will be added as a subject complement (e.g. The actor Russell Crowe told reporters that...)

Now, I'm a little confused about this, because I don't think that most scientists actually sign on in order to be famous. We'd all like to discover DNA, say, but we know that such paradigm shifts are rare and as long as we can persuade the granting agencies to continue our secret projects to maintain secret cheese-making factories on the moon staffed entirely by Lego® Mindstorms™ robots, we're happy.

Our agitator, however, demands recognition on behalf of all scientific disciplines and exhorts us to rise up and be counted.

It's not true, anyway. Randomly clicking through the BBC News to find evidence for or against his hypothesis (see? Science. Testing things) I found the headline

A greener way to recover methane

that says

A report in Nature has shown how crude oil in deposits around the world is naturally broken down by microbes to methane.

Scientists say that increasing microbe activity. . .

So far, so consistent with. But then, four sentences (and don't get me started on the whole 1 sentence = 1 polypeptidearagraph thing) further on,

"The main thing is you'd be recovering a much cleaner fuel," says co-author Steve Larter, a petroleum geologist from the University of Calgary.

I would not have bothered bringing this to your attention, but my eye was caught by someone at Imperial College, who writes

Prof Sian Harding was featured in the Sunday edition of The Star. She's one of the research groups in my department. My dad asked why was she featured and not my bosses. Well, its because:

1. She is a pharmacologist and therefore huge clinical potential aka more relevance to everyday life.

2. She has a huge lab made up of an army of lab butt monkeys aka phd students and post docs.

and the clincher?

3. If anyone from the media tried to contact my boss, he would probably tell them to sod off.

There you go. The last thing we want while ironing out bugs in secret cheese-making etc. is some damned journalist wanting to know our name (thank you, John Proctor).

"Is that a Gilson in your labcoat or are you just pleased to see me?"

One of my spies has reported back from a Biochem/Mol Biol Education Meeting held Dahn Sauf (in Melbourne. Poor chap).

Some interesting results from a survey of Honours Students. Apparently, 'going in' they wanted to get

more knowledge of XXX

experience with techniques in XXX

writing skills, public speaking, time management, critical thinking, etc.

I think that's actually a 'win' for the educators. Techniques and knowledge of facts are good to have; but if you're a half-way decent scientist you'll know where to find the facts, and how to learn the techniques, which is much more valuable (in my opinion) than the dry knowledge.

I'm particularly impressed that students came away thinking that they'd learned how to think critically. That's possibly the most worthwhile thing about the Honours courses we offer, and it is gratifying to be able to watch a naive student develop this faculty as she progresses through the year.

On which note, a shout out to my very young apprentice for his first class Honours, and a big shout out to the very young apprentice of Dr Choo, who scored a University Medal^[1]. Mad props and best wishes to them both.

Now that's what I call a scary error message.

We wants one of these. What's really cool is that they'll etch one with any PDB ID you care to give them.

How utterly awesome is that?!

(You may have to select a currency then go back and click that link again. Crap website, nice shiny things).

Seen while reading a journal's website:

Oh, if only.

You've probably heard how Jimmy Wales is talking up Wikipedia, the encyclopaedia where any— no, we've done that joke already.

Wikipedia has introduced a system of peer review, as if this solves anything. The problem is with the word 'peer'. If articles were guaranteed to be edited by people who know what they're talking about, then it would be fine. But you have no such guarantee, and in esoteric subjects (much of science, for example *cough*) you can not be sure that another student (a 'peer'), for example, is not deliberately falsifying entries to steal a march on the competition. Paranoid, moi?

You betcha.

As my friend Mark puts it:

I am not in favour of citing Wikipedia as an "authority", if by this we mean using it as a means of establishing points without any further discussion. I encourage my students, who are preparing for examinations at the moment, to engage critically with a range of secondary sources, one of which may indeed sometimes be Wikipedia.

And of course, with access to a University library, there is no excuse for not critically reviewing the primary literature, and doing your own fact-checking.

One of the things that we are learning in the doing of Science is that, fundamentally, all things are interconnected . Nowhere is this more apparent than in the familiar Central Dogma, the formation of protein from DNA through the intermediation of RNA.

For years the textbooks have viewed this process in three, discrete steps:

1. Transcription (DNA -> pre-mRNA)
2. Processing (pre-mRNA is capped, spliced, tailed and exported from the nucleus)
3. Translation (RNA -> protein)

Although we have long believed that these events happen almost simultaneously to any given 'message' in bacteria, the confounding presence of the nucleus has led us to believe that the same steps in real cells are spatially and temporally distinct. It turns out that this view is untenable.

Not only do bacteria have a nucleoid, the structure of which can influence gene expression in much the same way as eukaryotic chromatin, but the process of transcription-processing-translation in eukaryotes is much more coordinated than was once thought. Capping and splicing seem to be simultaneous with transcription, and export from the nucleus is similarly coupled to transcription and splicing.

Naturally, you only want your ribosomes to see to capped, spliced and polyA-tailed mesenger RNA, which then must be prevented from returning to the nucleus (see Ratcheting mRNA out of the Nucleus by Murray Stewart, and references therein). But how to do this?

The first thing you can do is let everything out of the nucleus, look for stuff that hasn't been correctly spliced &c. and destroy it. A more efficient method, and the one that the cell seems to favour, is to stop incorrectly (or incompletely) processed RNA from getting exported in the first place:

There is a nuclear pore-associated protein called Mlp1 that retains intron-containing RNA, i.e. unprocessed mRNA, at the nuclear pore. This binds to something called Nab2, that in turns binds RNA itself and the mRNA export factor Gfd1 .

Nab2 is potentially a marker for 'mature' (processed and export-ready) mRNA. It has a compact N-terminal domain (i.e., at the start of the protein sequence) that despite looking like a well-characterized RNA-binding domain actually is necessary and sufficient for binding to Mlp1.

By using my NMR structure (left) as a starting point for molecular replacement, Murray was able to solve the phase problem for the 1.8Å dataset obtained from crystals of it. Furthermore, a single mutation in the middle of the domain, that did not negate its binding to Gfd1, completely knackers binding to Mlp1 (much thanks to the yeast people in Atlanta).

So know we have another little piece of the RNA export puzzle. You can read all about it (and what the reviewer said).

Fields marked with an asterisk * are required.

So what do you do when you're learning to drive a (different) confocal microscope, it's half past 5 on a Friday, and you're only halfway through a 78 image Z-stack?

That's right, you muck around on the internets.

Failing that (because I don't know the password to the USyd cache and so can't actually get out of the building. . .) here's a random picture of what I'm doing:

No, I don't know what it means either. Damn, but I need a beer.

I've seen the way some of you do science. I'm not eating anything you've cooked. Ever.

From Propter Doc. So funny, I had to share.

(Although why she finds sandwiches "philosophically questionable" I do not know).

Science is supposed to be pretty. Not a lot of point in doing it, otherwise (for a range of values of 'pretty', at least).

So I was first pleased when I saw that an editorial Nature Cell Biology talked about the visual aspects of our work, and then disappointed when there were no accompanying pictures or movies to illustrate the point. Moreover, the link to 'further reading', which I clicked upon with great glee and haste, is empty.

Muppets.

Anyway, I got an email from Laura at the EMBO Journal last night. They are running a cover art competition;

The editors of The EMBO Journal are pleased to announce a new contest to select the best cover image for 2008.

As in the previous years, one winner will be selected from each of the two categories: Best Scientific Cover and Best Non-Scientific Cover. The prize for both winners will be a free one-year print and online subscription to both The EMBO Journal and EMBO reports.

This is a fantastic opportunity to indulge the artistic side of your scientific temperament. It's a shame that no one outside science will probably ever see your work, and the prize is hardly something that will appeal to someone with institutional access, but that's just quibbling. The closing date is 18 January 2008. Get snapping.

This is a message for local people. . .

Dodging the rain on the way to Redfern last night I found an eppie:

It says

EcoRI-IL6 150 ng/µl 11/'07

lin-IL6 150λ

At a guess it's linearized IL-6 DNA. If you want it back (long shot, I know), give me a shout. I want to know where you get your labels from if nothing else.