Microbe Processors

gpmap writes "Smart microbes are closer to reality than you might think, as described in an interesting article on Boston Globe Online. Ron Weiss, a Princeton biochemist, has already programmed E. Coli bacteria cells that release a fluorescent protein when they're exposed to certain chemicals. Now that a team at Stanford University has found a computer-based way to make cells react to any known chemical, the idea of weapons-detecting microbes looks even more promising. That is just one of the more modest applications of a remarkable new engineering discipline -- the science of programming cells. Imagine thousands of preprogrammed cells coursing through your bloodstream, checking cholesterol levels and patrolling for cancer. Or an army of bacteria powerful enough to suck the unwanted contaminant out of a whole lake, but smart enough to turn themselves off when no longer needed."

Comments

It's interesting...

[TitaniumFox]

...to see the interface between engineers of two different fields. I would have expected to see more knee-jerk "OMFG" posts speaking about the supposed dangers of this, and it's refreshing to see that there's few. It's also nice to see a post get into the nitty of nucleotides, Watson-Crick base pairing and the base pair wobble rules.

For those concerned about unleashing a transgenic bacterium into the wild that could have horrible consequences, consider the following (wrt. academic research): The E. coli used in research labs are most often "recombinant deficient," and viruses are most often "replication deficient." What this essentially means for E. coli is that genes coding for proteins that integrate foreign DNA into the bacterium's genome have been "knocked out" by one method or another (gross mutation, removing significant chunks of promoter sequence and coding sequence, etc). Plasmids carrying the ampicillin resistance gene that are subsequently transfected into the bacteria confer ampicillin resistance to those that carry it, and even replicate to a high copy number within the individual bacteria, but the ampicillin resistance gene does not get integrated into the host genome. Unless the culture is grown in a media that has a constant selection pressure (ampicillin), the bacteria tend to lose their plasmid. Keep in mind that Amp is heat labile and generally has a short half-life at 37 degrees C.

Likewise, replication deficient virus vectors have certain necessary virus sequences (certain packaging genes, promotor sequences, and long terminal repeats), but they also lack the crucial coding sequences that would give them the ability to become harmful and fully replicative. Example: A lentivirus (a subset of the retrovirus) vector can be made to be self-inactivating once it integrates into the host's genome. Additionally, for a researcher to make virions, they must transfect the virus vector into a transgenic "packaging" mammalian cell line that produces the viral coat proteins. Once you have enough of a virus titer, you use these virions to infect other cell lines (which are minus the genes that code for the coat proteins).

In a lot of cases, removing any coding sequences for proteins that facilitate DNA recombination in a host makes this sort of research quite safe when carried out under Good Lab Practice(tm).

While scientists are generally held closely to the ideals of the scientific method by their peers, there are protocols for minimizing risk (using recombinant minus host organisms), and these must also be followed. No scientist wants to be known throughout the world as the one who unleashed the monster.

With respect to the original story poster's comment about "turning themselves off:" It may have caused some confusion. The action of a cell responding to a chemical presence is usually through an inducible promoter system. The presence of a chemical catalyzes the recruitment of transcription mechanisms to the necessary location so they transcribe mRNA that codes for whatever the response is. In this case (as in indicator), it's the enhanced green fluorescent protein (EGFP). If you remove the chemical, the transcription machinery isn't mobilized to the promoter, and ultimately, EGFP isn't produced. Quite elegant. Do some searches for the lac operon or the trp operon if one is curious.

To end this and tie back into engineers of 2 different fields, a molecular bio grad student around our lab often wears the "Code Poet" shirt from ThinkGeek. I tend to think it's as in context as in CE/CS, wouldn't you? DNA is code of the most ancient sort. After looking at lines of ATG GTC CCA CGT CAC... for a while, one could liken it to assembler.

We haven't figured out our compiler fully, though.

Cheers!