Engineering a stripped-down bacterial drug factory

Researchers have deleted large chunks of a bacteria's genome in order to focus the organism on a single function: making drugs.<BR><BR><a href='http://meincmagazine.com/science/news/2010/01/engineering-a-stripped-down-bacterial-drug-factory.ars'>Read the whole story</a>

 

[TokamakH3]

"The downside, however, is that you have to have complete knowledge of every step of the biosynthetic pathway, including every place where a chemical is siphoned off from the basic metabolism. For many natural compounds, we're not there yet." <BR><BR>It's more like most or pretty much all natural compounds, we're not there yet.

 

[Tekzel]

It seems to me that they might also be able to use this method to create super effective vaccines, just delete all the harmful effects of the bacteria. Instead of using tiny bacterium corpses, I mean. Which seems so morbid.

 

[b.essiambre]

DOI Link is not working. <BR><BR>Here is a link to the PDF:<BR><BR>http://www.pnas.org/content/ea...833107.full.pdf+html

 

[D_Homerick]

If nothing else, the 'cool factor' of synthetic biology is off the charts. It's amazing to me that we're getting close to being able build up from scratch, rather than just introducing a gene or two at a time and praying that everything works mostly like we'd expect.<BR><BR>I'm doing computer science these days, though I've had a fair bit of exposure to biologists' toolkits due to a stint in a Pharmacology lab. I've noticed that many of my peers in CS place evolved systems on something of a pedestal, but my background has led me to have a very different view.<BR><BR>My view tends towards thinking that evolution has created some truly incredible hacks, but that it's one shitty engineer and is the last one you should be looking to for design inspiration. Simply put, there <B>is</B> no high level design going on, and trying to reverse engineer the soup in our cells is maddeningly difficult and slow going. Partly due to imprecise hardware (such as receptors are never 100% selective for "their" signalling molecule, and DNA that happily carries along meaningless mutations so long as the organism doesn't break <I>too</I> badly) and partly due to design by historical accident (famously, take the Panda's thumb) all biological systems look to me to be a cluster of messy hacks. Some of the hacks are incredible, but just as often, it seems incredible that it works at all.<BR><BR>The thought that we can possibly build from the ground up, whilst having a solid understanding of each minimal component, really gives some hope that we'll eventually have the sort of rapid progress in engineered organisms that we've had in engineered everything else. Evolution simply doesn't care how complex something is -- it's not a barrier to further manipulations. For us, any way that we could possibly reduce the complexity by a few orders of magnitude would be a godsend.

 

[DeadCat]

Imagine that a certain amount of "pressure" is needed to get organisms into "evolutionary potential wells" (heh heh, quantum biology?). Nature does this quite randomly at the moment infinite monkeys writing Shakespeare's plays in action. Or for a more appropriate analogy, pollen floating on the wind.<BR><BR>Humans, however, can help. We can grab a flower, carry it over to another flower, shake it, and cross our fingers. This has actually worked out quite well for us. But it's still too...random. We're pretty smart now, with all this genome stuff.<BR><BR>Why carry the flower over, if you can tell what genes needs to be added, modified, or removed? If it creates the same product as 10,000 attempts at cross-breeding, is it any less natural than shaking flowers on each other?<BR><BR>It makes sense to start with an organism that is close to a desired set of traits, and then use deletion and addition to push it over the potential hump, guiding it carefully towards our desired well without the need for random mutations and recombinations to accumulate over generations. The new organism might be stable and competitive, probably much more so than bottom-up. Unfortunately, evolution might have bigger plans for our new organism, so we may have to periodically re-populate with pre-volved organisms to keep us from sliding around the well too much.<BR><BR>Perhaps...too competitive? Now that I think about it, inability to survive in the wild could be an attractive selling point of the bottom-up approach...

 

[dreemernj]

"Hey guys, I have a great idea! I'm going to make a super powerful version of a genital parasite. What could possibly go wrong?"

 

[b.essiambre]

Here is a link to a great talk that J. Craig Venter gave last summer about the type of work that Dr. Timmer mentions above in the Ars piece. <BR><BR>the talk is called : "From Darwin to New Fuels (In A Very Short Time)"<BR><BR>you have to scroll down the page (or search) to find the video.<BR><BR>http://www.edge.org/3rd_cultur...r09_index.html#video<BR><BR>the video offers very timely and interesting opinions about this area from the lead dog of the synthetic biology sled.

 

[D_Homerick]

<BLOCKQUOTE class="ip-ubbcode-quote"><div class="ip-ubbcode-quote-title">quote:</div><div class="ip-ubbcode-quote-content">Originally posted by Massspectacular:<BR>Here is a link to a great talk that J. Craig Venter gave last summer about the type of work that Dr. Timmer mentions above in the Ars piece.... </div></BLOCKQUOTE><BR>Thanks! Quite interesting so far, and there's quite a few other talks on that page that look interesting too.

 

[dnjake]

"In the end, both of these approaches will have their uses, and it's possible the two might ultimately be integrated into a single process"<BR><BR>Like everything else the timing and exactly what will work out is uncertain. Craig Vetner seems to have run into some unexpected problems with his approach. But it seems very likely that these steps are just the beginning of a trend that over the next fifty to one hundred years will have a larger impact on human life than the industrial revolution or the development of the computer.

 

[ZobarStyl]

<BLOCKQUOTE class="ip-ubbcode-quote"><div class="ip-ubbcode-quote-title">quote:</div><div class="ip-ubbcode-quote-content">Originally posted by dreemernj:<BR>"Hey guys, I have a great idea! I'm going to make a super powerful version of a genital parasite. What could possibly go wrong?" </div></BLOCKQUOTE><BR>Not sure of the sarcasm factor on this one, but these are not more 'powerful' strains at all. They're specialized for drug production by (in the case of Venter's <I>M. genitalium</I> system) stripping out everything non-essential in the genome, so they are unlikely to be hardy strains outside of the gentle environment of lab cultures.

 

[mitEj]

<BLOCKQUOTE class="ip-ubbcode-quote"><div class="ip-ubbcode-quote-title">quote:</div><div class="ip-ubbcode-quote-content">Originally posted by dreemernj:<BR>"Hey guys, I have a great idea! I'm going to make a super powerful version of a genital parasite. What could possibly go wrong?" </div></BLOCKQUOTE><BR><BR> Better make it atomic while your at it, all good mad science should have something atomic in there. It just adds flare.

 

[jeblucas]

It's also interesting to see bacteria (or CHO cells or whatever) used as drug factories in general--not just for stuff they craft naturally because they compete in soil, but for introduced genes/plasmids to make even human protein. The thought that say, Micera, is grown in big vats of hamster ovary cells and then slurped out of there is pretty amazing.

 

[Tundro Walker]

Tack on some surface receptors so it can mimic a person's cells without being attacked by their immune system, and some way to sustain itself while in the human body, then you can just inject the little buggers into someone.<BR><BR>For a straight vaccine, that sounds impractical. But when you think about blood oxygen scrubbers allowing a person to stay under water longer, or reactive structures that would sit dormant until a certain toxin was introduced into the body, then it makes sense.<BR><BR>In programming, I think we take it for granted we can just toss instructions around on the computer right and left so easily, we think we're that far ahead in bio-engineering, too. But bio-engineering is really damn complicated. That's why we're still cutting folks open to do surgery (which is quite barbaric given that it's the 21st century) instead of tossing them into a bacta-tank ala Star Wars.

 

[earl grey]

I would love to see how this type of work would play out with prions.

 

[kumquat]

Wow, I almost feel bad for the bacteria. I can just imagine tens of thousands of the poor things strapped to metal tables in a huge, sterile room with tubes and pipes running through them with a mad scientist looking down at them expressionlessly, heedless of the agony their twisted, mutated forms are feeling. Good thing they're too small to be cute and cuddly.

 

[HalationEffect]

<BLOCKQUOTE class="ip-ubbcode-quote"><div class="ip-ubbcode-quote-title">quote:</div><div class="ip-ubbcode-quote-content">Originally posted by kumquat:<BR>Wow, I almost feel bad for the bacteria. I can just imagine tens of thousands of the poor things strapped to metal tables in a huge, sterile room with tubes and pipes running through them with a mad scientist looking down at them expressionlessly, heedless of the agony their twisted, mutated forms are feeling. Good thing they're too small to be cute and cuddly. </div></BLOCKQUOTE><BR><BR>Considering the range of unpleasant things that various bacteria have been doing to humans for millennia, I think that a little turn-about is not only fair play, but long overdue. ;-)