Wednesday, July 29, 2009

Other: Blankets Huge Chemistry Nerds Knit

I haven't done any knitting in many years, but at one time, it was kind of my thing, instead of messing with plants. And for several years I was also very very bored, so I had a lot of time to do it, too. At the same time, I also had a chemistry degree, and a particular fondness for biochemistry, so it was only natural, in an odd, not-inevitable-at-all kind of way, that I would find a way to combine the two.

So I did a series of what I call "protein blankets." First, to explain protein: proteins are what do most of the actual work in your body: antibodies are protein, hair is protein, your metabolism is by and large executed by proteins. Your DNA contains, among other things, the instructions for making these proteins, and it works like this:

DNA is more or less a line of text. Different bases (adenine, cytosine, guanine, thymine) are attached to a backbone of sugars and phosphates, and these bases are read three at a time, and these base triplets determine how the protein gets put together. Proteins are made of twenty different amino acids, which can link together, also in a line, and their specific properties are determined by which parts of that chain are attracted to one another, or to water, or are repelled by water, and so forth. Each set of three bases specifies a particular amino acid for that slot in the protein. It gets complicated really fast, but the upshot is that just as DNA is a line of bases which read like CCT GCA ACG TCT CCC, the protein that is formed when these bases are read is also a line, of amino acids. (The particular example above would translate as proline-alanine-threonine-serine-proline.1)

So what I did for the blankets was, I assigned a yarn color to each of the twenty amino acids,2 and then knitted one row for each amino acid in the sequence until I was done, and then I went on to the next blanket. I don't know exactly how long it took to do this one, though the smaller ones, once I got a rhythm down, were taking me about a week each. (This is a week spent doing nothing but knitting and watching TV, granted.)

The blankets that result when this procedure is followed generally look like I was just grabbing random balls of yarn with no particular rhyme or reason, and are kind of ugly unless one knows why the colors follow the sequence they do. And even then, they're still ugly. It's just that the ugly means something.

They're also hard to photograph, but here is one:


That is the major prion precursor UJHU blanket. Major prion precursor UJHU3 is associated with, and found in high concentrations in, certain neurodegenerative diseases like Creutzfeldt-Jakob disease, fatal familial insomnia, kuru, and so forth. The animal equivalent would be the agents responsible for mad cow disease (bovine spongiform encephalopathy), though I don't believe it's precisely the same protein in both cases. I should probably look into that.

We don't know exactly what purpose this protein normally serves in the body, though the fact that everybody makes it, and yet we don't all have degenerative neurological diseases, suggests that it must do something. (Wikipedia reports that it might have something to do with forming long-term memories: we know Wikipedia isn't the most reliable source on these things, but these kinds of diseases do all involve the brain, so memory is at least plausible, and the article does contain a reference.) It's also not clear how the disease is actually triggered. Prions are thought to work when a protein normally found in the body is induced to adopt a different, unusual shape, and then this misfolded protein is able to induce other copies of the same protein to also adopt this altered shape. Over time, this results in small clumps, called plaques,4 of these misfolded proteins, which as they get larger interfere with normal function of the brain.

Most (all?) cases of prion-related disease appear to be the result of mutations in the DNA which encodes this protein, which in turn causes the amino acid sequence to change. In some cases, the eight amino-acid repeat of PHGGGWGQ on the left side of the blanket (It's mostly white, with a little pink and blue. It starts just after the left side and takes up most of the left third of the blanket.) may be missing a repeat, or may get extra repeats, either of which could change its shape and function. (Repetition of a chunk of DNA is known to happen, though ordinarily I think they're smaller chunks than that.) More commonly, certain kinds of damage to DNA might change a single base in the DNA, causing the body to use a different amino acid in the finished protein. In blanket terms, this would barely be noticeable: we're talking about a white line changing to a light green one, or a dark green turning into a different dark green. Although these changes are not huge, they can affect how the protein folds itself, making the bad, plaque-forming shape more likely and leading to disease over time.

The whole blanket thing is mostly just interesting because most proteins interpreted this way actually look like what they are: random assemblages of amino acids that happen to be good at doing something. If you don't know the background, the blankets just look like I was grabbing random balls of yarn out of a bin and doing a line or two of them and then reaching in for a different ball, and the blankets are ugly. I mean, the blankets are still ugly if you do know the background, but it's very much not the case that I was grabbing random balls of yarn. It's all very, very specific and precise: it only looks sloppy.

The picture above of the actual blanket is kind of crap, since I haven't figured out a good way to photograph them yet. I think the camera needs to be like ten feet away to capture the whole thing, but I can only get the camera eight feet off the floor before running into ceiling. So here's a kind of idealized version: same colors, same sequence, but in a neat, tidy computer file instead of as a blanket. Just in case anybody's really dying to try to read the sequence of colors for themselves.


Major prion precursor UHJU isn't my best protein-related work, I should note. Everybody's favorite is salivary glue protein sgs-3 from Drosophila yakuba, which I only have as a blanket, not as a computerized picture like the one above. Perhaps someday I'll figure out how to take better pictures. Zein, a nitrogen-storage protein from corn seeds, is also nice. If there is any interest, I may occasionally post more blanket pictures, assuming I can get better photos than this. And also I'll probably have to look up which proteins they go with: at one time I could tell them apart pretty easily, but it's been a while. I've also got an RNA blanket (potato tuber spindle viroid), a neon emission spectrum blanket, and other science-related stuff I'm failing to remember right now. 'Cause I'm a big nerd.

ADDITIONAL TEXT FOR BIOCHEMISTS:

The N-terminal end of the protein is on the left. This is a precursor protein: about 20 amino acids on the C-terminal side are cleaved off after transcription. I do not know whether there are any disulfide bonds between the cysteine residues, though I'd be surprised if there weren't.

For the right amount of money, I could be convinced to take requests. The best proteins to do are between 200 and 400 amino acids long. Although I said above that I used to be able to knock out a smallish one in about a week, I would probably require considerably longer than that to do one now, and I'm not sure how we could set it up so that neither of us could back out of the agreement once it was made. But if you have a particular pet protein that you'd really like a blanket of, well, I do still have a lot of yarn, and the husband would like to see it go away, so . . . my e-mail address is in the left sidebar.

ADDITIONAL TEXT FOR KNITTERS:

I maybe should have done stockinette stitch for this, as it would have left me a smoother, more finished-looking surface in the end. Unfortunately, when I started these, I could knit but not purl, and even if I could have purled, the blanket would have curled up on me, which is not a particularly desirable quality for a blanket.

Of course, the stretchiness of the all-knit blankets leaves something to be desired, too. I'm really a very unsophisticated knitter (or, you know, was, since I haven't done any knitting in about three years). The blankets work more on a, you know, conceptual level.

If I had a whole lifetime for knitting and didn't have to take care of plants and stuff, I'd do some of the spider silk proteins: a lot of them would wind up very pastel (white, light green, aqua, lavender), and they'd maybe be nice for a baby blanket or something. Though it'd be weird to notice that you were wrapping your baby in spider silk, even if only on a really meta level.

-


1 For the sake of convenience, faster typing, etc., each of the amino acids has been assigned a single-letter abbreviation. Our example, in the single-letter code, would be "PATSP". (What a crazy random happenstance!)
2 Alanine (A) -- light green
Cysteine (C) -- yellow
Aspartic Acid (D) -- red
Glutamic Acid (E) -- dark red
Phenylalanine (F) -- black
Glycine (G) -- white
Histidine (H) -- medium blue
Isoleucine (I) -- dark gray-green
Lysine (K) -- dark blue-green
Leucine (L) -- dark green
Methionine (M) -- orange
Asparagine (N) -- light pink
Proline (P) -- aqua
Glutamine (Q) -- medium pink
Arginine (R) -- royal blue
Serine (S) -- lavender
Threonine (T) -- royal purple
Valine (V) -- kelly green
Tryptophan (W) -- brown
Tyrosine (Y) -- dark purple
Readers with some biochemistry knowledge will recognize that for the most part, I've coded small amino acids with light colors and heavy amino acids with darker ones. Also hydrophobic amino acids are varying shades of green, basic amino acids are shades of blue, and acidic amino acids or their close relatives are shades of red and pink. Purples indicate neutral hydrophilic groups, and yellow and orange involve sulfur.
There are some things I'd change about this setup now. Like, methionine really should have been more of an acid green / chartreuse color, cysteine should have been a pastel yellow, lysine should have been more of a straight blue, and asparagine and glutamine maybe should have been purplish (maybe fuchsia/magenta). But I was also having to make do with what was available at the Wal-Mart in town, too, and they had a limited range of colors.
3 I think the "UJHU" part is an internal identifier code for this particular protein at the specific site where I got the sequence, and not, properly speaking, part of the protein's actual name. I include it anyway because, in theory, this will make it easier to look up. Incidentally: uniprot.org is incredibly slow and balky looking anything up for me, so don't take it personally if you have to try multiple times to load the page. It took me, no lie, like three hours to find and load the pages. I don't know what their problem is.
4 Totally different from the plaque one gets on one's teeth, though.


23 comments:

Frances said...

Okay, Mr. Sub, this is one interesting though odd post on a garden blog. I followed as best as possible and am also a knitter, if a novice, and no scientist at all, but rather an accountant. All knitting is what I like to do just for the sake of mindless finger movement in the winter, no purls, using fabulous alpaca yarn spun by a lady here who raises her own and dyes it herself then spins it. I unravel each item to reuse the yarn, it is the process rather the the finished product that appeals to me. Your code for the colors is otherworldly and I don't find it ugly at all. More of this please.
Frances

Paul Anater said...

Bravo Mr. Subjunctive. I love seeing science-y stuff re-interpreted and your blankets are extraordinary. You have an amazing mind and thanks for granting your readers a small glimpse of it.

mr_subjunctive said...

Hey Frances.

Well, I only promise one plant-related post a day. After that I get to wander a bit.

I suppose that was some of what I liked about it too, just the movement of it. It was also semi-practical because I was living on an unheated porch (in Iowa) for a lot of that time and needed all the blankets I could get, but that's another story. The idea of going to all that effort and then unraveling it all, though, kind of pains me in a weird existentialist way.

Paul Anater:

Have you seen the quilt some lady did from a gene for something? I'll look for it on-line. (I just saw it a couple days ago, actually, so hopefully I won't have to look long.) It's pretty cool, in a similar random/ugly way.

mr_subjunctive said...

Ah, yes. "Genome Quilts" by Beverly St. Clair:

http://genomequilts.com/genome.php

Zeï said...

The ugly means something, and indeed, that makes it pretty to me! Wonderful work, no doubt. And this post drove me back into hours of studies for my first molecular and cellular bio course in university!

Wicked Gardener said...

I have to say - not so ugly. It is not completely random, which adds a certain movement. I like 'em. I used to knit too, and would think of the stitches as computer language - all 1's and 0's. Reading your post made me feel slightly less crazy.

RJ Flamingo said...

I don't find the blankets ugly at all, and actually pretty fascinating. From a photography standpoint, you might want to try hanging them, or just spreading them out on the back of the couch. We'll get the idea.

Definitely worth a ReTweet! :-)

mr_subjunctive said...

Zeï:

Are you liking the molecular biology so far? Or not so much?

Wicked Gardener:

Aw, thanks. Though I think your comment makes me feel slightly more crazy.

RJ Flamingo:

Part of the problem with trying to hang them from something is that they're very stretchy and heavy, so it takes a lot to hang them on a wall. Throwing one over something might work better, but depending on the blanket, it may have to be a really long something. Perhaps I'll try the bed, for future blanket photos, though that still leaves the problem of how to get far enough away. Many of them are bigger than the prion protein blanket, and for that picture I had the blanket on the floor and I was standing on a table, and I still wasn't far enough away. We'll work on it, I guess.

Wicked Gardener said...

Erggg - See what happens when I try to compliment someone? ;D

Kenneth Moore said...

I felt a sense of complete surprise, as well as a feeling of confirmation, upon reading this post! I suspected you had a science background, but I was made happy at the discovery of your knitting abilities. I have never attempted anything as grand as your protein blankets--either in terms of size or concept. But I do have a 10-foot-long, 1-foot-wide scarf that I knitted. I don't know how to purl, so I just flip it over, and it gets a nice ribbed effect. I made so many scarves while watching reruns of Buffy during finals weeks... Tonight, actually, I crocheted a cell phone carrying case--I somehow dropped the previous one over the weekend.

But, on to the requests! Cytochrome p450 from Pseudomonas aeruginosa, please! Any such monooxygenase has pretty well-conserved sulfide-bond and heme regions, but the rest of the areas tend to more variable, so if you do a collection of them from different organisms, there will be many portions of the blankets that look the same with areas that (sometimes widely) different. It has 418 amino acids, so that might be too large... Maybe it could be a series of pot holders instead?

mr_subjunctive said...

Kenneth Moore:

Well, I did say I could be convinced for the right amount of money, ahem ahem.

I'd considered doing blankets like what you're proposing, with different versions of the same protein all sewn together, but one of the problems with that, besides it being a lot of extra time and work, is that the proteins are often not all the same size, and I could never figure out how to put those all together in a way that looked reasonable. Also sometimes the sequences are very different, even when the proteins do the same thing and have the same general shape, so there are no real obvious homologies to be seen anyway.

lynn'sgarden said...

How is possible that one can create such beautiful textile (not to mention visual) art and have it associate with bio-chem?! I find it amazing that that much thought process went into the next choice of color! Love the methionine bands best. What length needle did you use for this? It's into Aug and I'm still knitting wool socks (a pair a weekend) for the long-xmas list! So impressed with your talent, Mr. Subj...Pure awesomeness, this post!!

mr_subjunctive said...

lynn'sgarden:

What length needle? Um. I'm not sure. It was probably something like 12-14 inches. Not huge. I had to stop a lot during any given row to push the stitches back so I could continue.

no1uno said...

excellent post and a great original idea. I like the tie-in with a disease-causing prion. I see blankets/scarves/hats knitted with your yarn code being auctioned off to raise money for research/cures/treatments for various diseases. Like BRCA1 for breast cancer or CFTR for cystic fibrosis. You would not be expected to knit all these items of course! Great work and personally, I love look of the blanket.

Paul Anater said...

Thanks for the referral to the Genome Quilts. I am convinced that art and science are not in opposition at all, they are in fact the same thing --humanity's creative energy at its best. Your protein blankets and now these Genome Quilts validate my ideas. Thank you.

CelticRose said...

That, Mr. Subjuctive, is art. Not ugly at all. I would love to see more of these.

For future projects, scarves sound like a good idea.

Have you seen the DNA scarf?
http://www.twosheep.com/helix/
I've definitely got to knit that one someday.

mr_subjunctive said...

no1uno:

I hadn't considered them as fundraiser-related before, though obviously they could be. There's a bit of a problem with how to choose the proteins in question: BRCA1 is 1,863 amino acids long, making it more of a mural than a blanket (or, alternately, a series of six blankets, I guess). The CFTR (cystic fibrosis transmembrane conductance regulator) gene is almost as bad (1,480 amino acids). So it'd either only work for certain diseases, or the blankets would have to be edited versions of the proteins (doable, but it offends the purist in me).

CelticRose:

The DNA scarf is way the hell beyond my abilities as a knitter.

After reading through the comments, it has occurred to me that there's probably a way to get the plant interest worked in there too, along with the chemistry and knitting. What indoor gardener wouldn't want to have a squalene synthetase from Euphorbia tirucalli blanket (411 aa)? Or the mannose-binding lectin protein from Monstera deliciosa (283 aa)?

And of course outdoor gardeners might be interested in 4,5-DOPA dioxygenase extradiol from Portulaca grandiflora (271 aa). Or maturase K of Tagetes patula (391 aa). Endless possibilities.

Damnit, y'all are going to get me wanting to start knitting again, aren't you? I definitely need to find some way to automate the knitting process, in that case, 'cause no way could I keep up with the blog, the plants, and cranking out blankets at the same time.

lynn'sgarden said...

LOL!! Picturing you tripping thru the house with skeins tangled around your feet and trying to water those pots..but, hey! if there's a will...
Just don't lose the blog :0

Zeï said...

Less than the cellular and organism biology, I must admit, even though it is closely related. It seems the molecular level is not something I can easily compute by itself alone, and that makes it less interesting to me as opposed to cellular-organism bio.

CelticRose said...

Lol, I meant do your protein sequences as scarves. ;-)

As for time to knit, the lovely thing about knitting is that it's portable and garter stitch doesn't take much thought. You could do it while sitting in car (as a passenger, of course!), while watching TV, etc.

Lance said...

I don't find it ugly at all, I know very little chemistry, or should say what little I knew left a long time ago. But I love the design and unusual look.

Paul said...

While I would not say the blanket was incredibly, stunningly beautiful, I would not call it ugly either. I did find it quite a novel concept and definitely interesting to gaze upon.

I would like to see your other blankets and to hear about the proteins that inspired them.

Very good, Jas!

Beth said...

I'm a knitter and I think your blanket is lovely. I'm so glad I stumbled upon your blog; will become a regular reader.