In which we go a little cycle-pathic

For most normal people, a Sunday afternoon in London might find you down the pub having a lovely roast dinner, a lukewarm pint and a chat about the torrential winter rains or the rugby. But not us geeks: we’ve got standards to maintain. It’s not just a Monday-through-Friday, nine-to-five job – neither rain nor snow, nor sleet nor dark of night shall stay these quirky obsessives from the swift completion of their appointed rounds.

This past Sunday, Eva, Richard and I were sitting around my Docklands flat. Eva, on a flying visit from Toronto, had just about dried off from her swim from the Tube station and was getting her strength back with a bowl of pasta. I was trying to hold up my end of the conversation while finishing up an opinion piece for Nature, and Richard was mixing things up a bit by fiddling with his iPhone instead of his laptop. Plans were afoot for interviewing Eva for a LabLit podcast down at the local watering hole later about something suitably sci-lit geeky.

I’m not sure who brought up the topic first, but Eva mentioned she’d like to do some sightseeing in Cambridge, and Richard told us about the BRCA2 Cycle Path, part of the National Route over a mile between Addenbrooke’s Hospital and Great Shelford. As a public engagement exercise, the path had been painted in 2007 with about 10,000 stripes of four different colors, each representing a nucleotide base and collectively spelling out the entirety of the gene BRCA2. Residing on chromosome 13 and associated with breast cancer in mutated form, BRCA2 was sequenced at the nearby Wellcome Trust Sanger Institute, who sponsored its enshrinement on pavement.

Now, this is old news (which R. has blogged about here and here). What I want to talk about now is how a random trio of geeks, in their natural habitat, handled this conversational turn.

What exactly, we wondered first off, was meant by ‘gene’? Richard googled up a photo of the start of the cycle path, and we gathered round the screen:

Green, red, yellow, blue, blue, red, green, red, red, yellow, yellow…

Eva and I reckoned that the logical choice for the designers would be the beginning of the coding sequence; therefore the first codon would be methionine, making green an A, red a T and yellow a G (and blue, C by default). I voiced my doubts straight away: most Kozak consensus sequences place a G after the initial ATG, and that didn’t fit the pattern. Plus the size of the protein would be monstrous: ten thousand base-pairs /3 bases per codon = 3.6k amino acids x 110 daltons/aa = 396 kD – a huge protein. This cheered up Richard considerably: due to his background, he is quite mRNA-ocentric, forever going through life biased towards consideration of untranslated regions.

Abandoning my Nature piece, I navigated into the NCBI Entrez website and pulled out a representative messenger RNA sequence; the protein was indeed that huge, but I failed after only a cursory scan to see a start codon that matched the pattern (and was too lazy to put some welly into it). Eva pointed out that there were 4! (4x3x2x1 = 24) possibilities matching colors to bases, so searching for all the permutations by hand just might be too much hard work even for geeks on a Sunday. Richard transcribed the first 20 stripe colors from the photo and performed a Blast search on the assumption that the first stripe was an A, but didn’t get any hits in BRCA2. When Eva suggested he try all 24 possibilities, Richard briefly considered, then abandoned, writing a Perl script to do it for him. Instead, he had a search through Entrez, pulled up another mRNA sequence and searched for the presumed starting-with-ATG string, not by eye but with Apple-F, until he found an ATGCCTATTGG that matched the cycle path colors.

Another job successfully completed – but a geek’s work is never done. Borrowing just a little from Jane Austin, if anyone has any other cycle paths that need decoding, please send them on, for we are quite at leisure.

About Jennifer Rohn

Scientist, novelist, rock chick
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61 Responses to In which we go a little cycle-pathic

  1. Richard P. Grant says:

    Yeah, that’s about how it happened.

  2. Jennifer Rohn says:

    I pulled out all the novelistic stops to make you sound more heroic.

  3. Richard P. Grant says:

    I’m merely the hired help, I know this.

  4. Eva Amsen says:

    The best part was where I (jetlagged, soaked) could do 4x3x2x1 in my head, but Richard used a calculator and several seconds more.

  5. Åsa Karlström says:

    so, where are the photos from the actual bike route? Or did you never go? 😉
    [I find the conversation slightly disturbing but since I am sure I would geek out in a similar matter… 🙂 ]

  6. Eva Amsen says:

    I ended up doing a walking tour in Cambridge, and it was almost as geeky. Will blog later, but need to do some actual work. As opposed to “calculating permutations of a cycle path”-work.

  7. Kate Grant says:

    That’s actually kinda cool – we heart geeks.

  8. Åsa Karlström says:

    Eva> I saw the path when I was in Cambrige last summer. I remember thinking that I should have gone…. but then again, I opted for book shopping and going into the Monsoon store with 40%

  9. Jennifer Rohn says:

    Asa, I am ashamed at how shallow you are! Monsoon and a curry…tut tut.

  10. Richard P. Grant says:

    Eva, as I pointed out at the time, I was confirming to my own satisfaction that the function was a factorial. Seeing as I have nothing above ‘O’ level maths these things are important to me. We can’t all be human calculators.

  11. Jennifer Rohn says:

    I initially thought there would be only four searches required – but I suck at math. That’s when Richard likes to be around me – because it’s all relative.

  12. Cath Ennis says:

    Ah, but does the path represent the wild-type sequence, or one of the common mutations?
    Please check and get back to me, kthxbai

  13. Richard P. Grant says:

    Next time I cycle it, I’ll check, Cath.

  14. Jennifer Rohn says:

    I was thinking at the time that it would be a nice trick to have pained two stripes side by side for the key mutations (I’m assuming they’re SNPs and not indels), but it’s the wild-type, I believe. If there were any indels, it’d be a nice touch for them to have made little short-cur detours so you could choose to cycle either wild-type or disease-mutated, depending on your mood on the day.

  15. Richard P. Grant says:

    Cambridge is full of mutants as it is.

  16. Jennifer Rohn says:

    Pained? Painted!
    Sheesh. I plead Cheetos withdrawal.

  17. Ian Brooks says:

    bq This past Sunday, Eva, Richard and I were sitting around my Docklands flat.
    Ecxellent story of geek detectivery, and +1 for making homesick within your opening lines!

  18. Jennifer Rohn says:

    A rugby man, are you? I like that version where they pull each others’ trousers down.

  19. Cath Ennis says:

    A quick PubMed search tells me that SNPs and indels are both pretty common.
    I’m sure there’s some kind of cycling / frameshift joke in there somewhere, but it is currently eluding me.

  20. Richard P. Grant says:

    Was your train of thought de-railleured?

  21. Cath Ennis says:

    and there we have it.
    I spoke too soon!

  22. Richard P. Grant says:

    I’m tyred of this.

  23. Jennifer Rohn says:

    You might want to back-pedal and reframe the question, then.

  24. Richard P. Grant says:

    Get to the hub of things, you mean?

  25. Jennifer Rohn says:

    /tries and fails to come up with a pun using the phrase ‘quick release front tire’

  26. Eva Amsen says:

    They should make a path where it’s a frameshift mutation. It could be like a T-crossing where one direction is wildtype and the other is the mutation. If you choose the frameshift mutation route, the path only goes on for a little longer, and then suddenly crashes off a cliff or into a lake!
    Hmm, I wonder why they didn’t do that….

  27. Jennifer Rohn says:

    It’s not very sensitive to make fun of people suffering from premature stop codon.

  28. Cath Ennis says:

    Modification by microRNAs could be symbolised by kids chucking stones at you to try and knock you off your bike (this actually happened to me in Glasgow)

  29. Henry Gee says:

    I don’t get invited to that kind of party. Thank God.

  30. Jennifer Rohn says:

    What about methylation?

  31. Richard P. Grant says:

    So in that model, Cath, the cyclist is the ribosome?
    Methylation would be some scrote with a spray can of paint.

  32. Jennifer Rohn says:

    An IRES binding protein would be some interloper coming up out of the ditch and joining the path part way in.

  33. Cath Ennis says:

    So in that model, Cath, the cyclist is the ribosome?
    Methylation would be some scrote with a spray can of paint.
    Or, drawing on my Glasgow experiences again, liberal sprinklings of broken glass.

  34. Jennifer Rohn says:

    Damn…sorry to hear that!

  35. Richard P. Grant says:

    Hmm, sounds more like a macrolide to me.

  36. Cath Ennis says:

    Yeah… after the third puncture in six months, I had to resort to lining the outer tyres with old punctured inner tubes. It made the bike a hell of a lot heavier, but I only got one more puncture in the next three years.

  37. Cath Ennis says:

    I had to look up macrolide.
    This thread officially Too Geeky For Me now.

  38. Jennifer Rohn says:

    There must be a DNA repair analogy in there somewhere.

  39. Cath Ennis says:

    Gaah! I just left an awesome, potentially genius, comment with all kinds of hilarious links, and it seems to have disappeared. Is it stuck in the spam filters?

  40. Matt Brown says:

    Yes, it was Cath. But I have unleashed your genius.

  41. steffi suhr says:

    Is it me, or are Cath’s links all going to the same page?
    P.S. You guys are crazy. Asa, can I go to Monsoon with you?

  42. Stephen Curry says:

    I’m afraid it’s you Steffi. Cath’s genius links work fine for me…

  43. Jennifer Rohn says:

    I like the geeky way that Matt was lurking in the background, ready to pounce upon the problem. Sir, we salute you.

  44. Nicolas Fanget says:

    Methylation could be sleeping policemen, to provide a more “interesting” ride. It would be great to design a route where you can follow the exons/introns, to produce different forms of a protein. I’m not a human biologist, but I seem to remember the genes involved in cystic fibrosis might be good for that, it’s huge!

  45. Jennifer Rohn says:

    How about a really heinous stretch of secondary structure? A big fat hairpin that you have to pedal up and down? Good for the thigh muscles.

  46. Samantha Alsbury says:

    This has brightened up my lunch break considerably – I salute you all!

  47. Nicolas Fanget says:

    The gene of course, not genes. I second Jennifer about secondary structure, RNAs would do great mountain biking trails! Although this

    (available at your favourite journal starting with N here)
    reminds me a bit of Milton Keynes, the only time I went there I got lost with a sat nav!

  48. Jennifer Rohn says:

    Hahahaha! Fabulous. I’m starting to a great idea for a whole host of geeky theme park rides. The Ultracentrifuge…the Electrifying Electrophoresis…the Western Blot…
    Or how about a house of horrors entitled ‘The PhD Experience’? The punters will be gibbering by the end of it.

  49. Åsa Karlström says:

    Steffi: Of course. I love company when trying on clothes and dreaming about silly times to use the flimsy dresses 🙂
    Jenny: didn’t you see that I went book shopping too? ^^ but sure, shallow thy name is åsa 😉

  50. Åsa Karlström says:

    Jenny: and in the theme I would LOVE a themepark like that. Imagine how you can structure the rides to the names! wow!!

  51. Darren Saunders says:

    BRCA2… welcome to my nightmare. Imagine having to actually work with this gene/protein. Yes, it is that big

  52. Cath Ennis says:

    Thanks Matt!
    The links are going to separate places for me, but not to the ones I originally inserted.

  53. Jennifer Rohn says:

    Darren – my condolences!
    I dreamed about my electrophoresis amusement part ride last night. Everyone was equipped with slightly different negative charges, which you could control, shooting down a slippery horizontal surface towards the finish line.

  54. Ralph Lasala says:

    What if a double strand break occurs?
    Nicolas, that does remind me of the roundabouts. Where are the cows?

  55. Jennifer Rohn says:

    Good point, Ralph – must incorporate some UV-like aspect to my ride. That would certainly make it more interesting!

  56. Richard P. Grant says:

    That would probably be a guy with a sledgehammer or pneumatic drill?

  57. Jennifer Rohn says:

    One of my friends on Facebook commented on this blog post as follows:
    ‘The stripes start less than a mile from my office, so it’s my running route on the very rare occasions I can sneak off for a lunchtime run. We’ve discussed fixing a webcam to a remote-controlled toy car, doing a bit of clever digitisation and writing a tongue-in-cheek paper on rubber-tarmac-interface induced mutations.’
    Maybe something for PLoS-One?

  58. Richard Wintle says:

    Goodness me, you lot are a dedicated bunch of geeks. And I thought sitting in the lobby of the Sanger Centre, and using an online (mRNA) translation site to decipher the gnetic code printed on the window, was geeky.
    /bows down to uber-geeks
    P.S. I’m not telling you what it said, you’ll have to Google go there and do it yourselves.

  59. Jennifer Rohn says:

    “No geeks beyond this point.”

  60. Richard P. Grant says:

    Real geeks would have done it in their head, Richard.

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