Hard Light Productions Forums
Off-Topic Discussion => General Discussion => Topic started by: Dragon on May 17, 2016, 10:05:42 am
-
OK, this one is just too great not to post. David Liu's group at Harvard managed to "weaponize" Darwin's evolution theory against insects:
http://blogs.sciencemag.org/pipeline/archives/2016/05/16/evolution-in-action-literally
That's one of the most awesome bioengineering techniques I've seen, and with enormous potential, too. In a nutshell, it's possible to set up a system in which a bacteriophage's ability to reproduce depends on the protein (and its functionality, of course) you want it to make. Derek Lowe explains it best:
Here’s how that works: the M13 bacteriophage have a specific surface protein, pIII, that they need for their progeny to be infectious. In this case, they’ve had that gene stripped out of their sequence, but it’s been added instead to the E. coli cells that they’re going to be infecting. That gene is set up, on an accessory plasmid (AP) downstream of a promoter that’s tied to the protein-protein interaction that you’re trying to evolve – so only when some protein can bind to its target up there will pIII get produced. That protein is what the phage are going to have to evolve to keep themselves reproducing – they infect the bacteria with a selection plasmid (SP), and if that plasmid DNA can generate a protein that starts the pIII production machinery, then they can get enough pIII for their progeny (being produced inside the infected bacterium) to be infectious in turn. The bacteria also have a mutagenesis plasmid (MP), arabinose-driven, that bumps up the rate of error-prone DNA copying, to keep a mutagenic foot down on the evolutionary gas pedal.
And here’s the final trick: the bacteria are in a “lagoon” vessel, and are being continuously dripped in (and the contents of the lagoon are being similarly slowly drained out. You tweak these flow rates to fit the rate of phage mutations, so that they’re in a constant fitness race. If they can evolve proteins to get their pIII protein and go on for another generation faster than they’re being diluted out of the lagoon, they’ll keep going. Otherwise, out they go. You have to play around with these, of course, so that you’re giving them a fair shot in their c. 20-minute lifespan: run things through too quickly, and the phage won’t have a chance, but if you do it too slowly they have no incentive to better themselves.
Using this, you could "evolve" protein variants that work on organisms resistant to the basic form. So far it seems to work with the Bt protein (a common insecticide that insects are evolving resistance to), but I can see this being of use for evolving antibiotics that work on resistant bacteria. And if they evolve to be resistant to those, we could evolve new variants again.
-
I feel like this is Xzibit's take on genetic engineering. :D
-
Ha, that's phenomenal. Reading stuff like this makes me kind of wish I'd continued on in grad studies for genetics. Then I remember how much I hated monotonous lab work.
-
Same with me and interesting physics articles. "Gee, this looks great, maybe physics weren't that bad after all..." *remembers tensor algebra* *Oh, yeah, they were that bad." :) Reading scientific papers is usually a lot more fun than actually arriving at the results presented in them. I can't even imagine just how much fiddling it could have taken to set that one up. This "playing around" with flow rates Lowe mentioned has probably taken a while to perfect as well. It must've been amazing to watch the resulting proteins utterly massacre those cabbage loopers, though. :) There's nothing in this world like a well-earned "It works!" moment.
-
*remembers tensor algebra*
A glorious orgy of indices!
-
the secret to tensors is to approach them from the maths end so they look like reasonable algebra rather than crazy, arbitrary matrix operations
-
TBH, the matrix form was actually hardly mentioned in the algebra course I took. It was all about the "maths end" and once I got this explained by someone who wasn't doctor Herdegen (let's just say he's not as good a lecturer as he is a scientist, though hardcore math types do find his style workable), understanding what they're about wasn't even all that hard. That didn't make associated index juggling any less tedious, though. :) Unfortunately, with tensors, even basic operations require an inordinate amount of fiddling. Sure, some are fine with it, but I'm more of a lab guy.