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We’ve just had a paper published and I would like to tell you a story about people in science being nice to each other – a thread cell.com/cell/fulltext/…
This is a large, collaborative effort – 54 authors across multiple institutions, led @MountSinaiNYC and @CVRinfo. But the science in the story is quite simple (and you can read it in the paper), so I’ll explain it quickly before telling a different story (which you cannot)
Briefly, here’s the science of it. THE BACKGROUND: (i) Viruses need to make mRNA that host ribosomes can translate into proteins Baltimore classification of viruses
(ii) Segmented negative-strand RNA viruses (sNSVs: influenza, lassa, the bunyas… there are a lot) make ‘hybrid’ mRNA by ‘cap-snatching:’ cutting the 5’ end off host mRNAs and extending them with transcripts of their own genes, which contain viral start codons Cap-snatching schematic
(iii) sNSVs only cut a short snippet of host mRNA, well upstream of normal host start codons. However, it’s becoming clear that many host mRNAs have upstream start codons (uAUGs, often regulatory) very close to the 5’ cap uAUGs in eukaryotic genes
THE QUESTIONS: does cap-snatching append these uAUGs to viral mRNAs (‘start-snatching’)? And if so, do this do anything interesting?
THE ANSWERS: Yes, and yes. As a result of cap-snatching, all sNSVs are capable of encoding additional genes – both N-terminal extensions of ‘canonical’ genes and short out-of-frame genes ‘overprinted’ on the canonical ORF like a palimpsest Palimpsest of Cicero's De re publica 1.17.26-27
THE IMPLICATIONS of this are wide-ranging, but for influenza A viruses we showed that some of these novel genes are translated, incorporated into virions, can be subject to immune surveillance and can modulate virulence. Here ends the science story…
… and now the other story, of how the paper came together. It has some useful messages in about #collaboration, #preprints and @Twitter. For clarity (because @CVRHutchinson is a group account), it’s also written from my perspective (#EdHutchinson)
It’s also quite long, arguably to the point of self-indulgence. You have been warned. Here goes:
For me, this paper started when I went to work as a postdoc with #ErvinFodor @Dunn_School. The plan was that Ervin would train me to be an RNA biochemist. To our mutual dismay, we found that I was not very good at this
It is credit to Ervin as a mentor that he kept me on despite this, and encouraged me to change tack and devise new projects that suited my skillset better. That’s how I ended up using #MassSpec A mass spectrometer
It’s also testament to Ervin’s generosity that, when I found a deeply weird peptide (spoiler: created by start-snatching) he encouraged me to use it (among other things) as preliminary data in an application to set up my own group @CVRinfo A peptide spectral match that is a lot more exciting than it
Once @CVRinfo, I recruited Liz “I’d like to do the high-risk project please” Sloan as a postdoc, who did loads of cool work on this. She’s now on maternity leave and the project was taken on by @Lea___Meyer, who is also fab
Great though Liz and Léa are, it was a complex project and we needed backup. Fortunately, scientists are a helpful bunch
Our friendly colleagues helped a lot: bioinformaticians and bunyavirologists @CVRinfo, and @megamacleod15 in @iiiglasgow for immunology (following an experiment suggested by my @acmedsci mentor) The MRC-University of Glasgow Centre for Virus Research
The wider community helped too. Chats at conferences led to repurposing unpublished data from groups @CamPathology and @roslininstitute, to carrying out pathogenesis studies, and to asking @thefluzee to reanalyse some of her cool CAGE data
So eventually we had a story more or less ready, and then someone mentioned that they had heard a seminar about a very similar project and had we seen their preprint? And it turns out that I had not been trained to react well to this sort of news biorxiv.org/content/10.110…
Fortunately, I was in @uofglibrary at the time, where loud swearing is discouraged
So, I took some deep breaths, had a cup of tea (@uofglibrary make pretty good tea), spoke to Liz and resolved to publish what we had ASAP
I approached @plosbiology, because I’d already had a chat about the project with one of their editors to find out if they might be interested in it, and also because they have a ‘novelty window’ in which they don’t penalise you for being scooped
So, we wrote up the paper and we did two things that I was unsure of. Firstly, we cited the other group’s preprint and discussed it even though it wasn’t yet published biorxiv.org/content/10.110…
Secondly, I was new to social media then and tried out tweeting about both of the studies, tagging the only author from the other study I could find
Two things then happened. First, @plosbiology sort of liked our paper (interested, but major revisions) and their reviewers actively supported the fact that we’d cited preprints Comments from a forward-thinking reviewer
Secondly, the lead author of the other study, #IvanMarazzi, got in touch. Ivan isn’t on Twitter (I think) but word had got back about the tweets Ivan Marazzi and a tiny horse
Ivan had an interesting proposal. Our studies were complementary rather than identical and he was, he said, fed up with competing against people for papers. Would we be willing to combine the studies into one publication, sharing first and last authorships?
So we got to work on that. The first thing to note is that @plosbiology were just great. They’d been fab to work with up to this point – clear, rapid responses, constructive reviews – and they were also extremely understanding when we then withdrew our submission
The second thing to note is that combining two massive studies is... challenging
It’s hard for the obvious reason (picking them both apart and putting them back together). It’s hard because you have to keep 52 co-authors in the loop and on board while doing that…
… and it’s hard because Ivan and I write in very different styles. I like to think the end result includes the better features of both of us. I certainly learnt how to put my own preferences aside for the good of the paper, which is an important lesson to learn
So now the paper’s out, I have an opportunity to thank everyone involved, most especially the efforts of #Liz and the generosity of #Ervin and #Ivan. None of them are on Twitter so I can say how great they are without embarrassing them
If you’ve read to the end of this very long thread you’ll hopefully take it as evidence that preprints and social media can be part of the development of a paper, and that as scientists we definitely can work together rather than against each other
Finally, you’ll also see that @Lea___Meyer has persuaded me to try and learn to use GIFs. Maybe they will be good for the paper too?
Probably there were too many of them
Ahem, that should have read @meganmacleod15 - sorry Megan!
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