IGEM:Caltech/2008/Ideas: Difference between revisions

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*One way to do this is to express mutiple tetR variants that have different affinities for aTc, the primary inducer used in bacteria. I have found one paper that reports tetR variants with different affinities <cite>tetR</cite>, although I'm sure more can be tracked down.
*One way to do this is to express mutiple tetR variants that have different affinities for aTc, the primary inducer used in bacteria. I have found one paper that reports tetR variants with different affinities <cite>tetR</cite>, although I'm sure more can be tracked down.


==Bacteriofood==
===Bacteriofood===
*After reviewing UC Berkeley's BactoBlood in the 2007 iGEM Jamboree, Bacteriofood could be used to produce and carry vital nutrients that can maintain a healthy human. Most useful in third world countries where food is hard to come around. Bacteria being easy to grow and maintain, could be a simple way to feed the underfed. Just trying to throw out any idea that comes across.
*After reviewing UC Berkeley's BactoBlood in the 2007 iGEM Jamboree, Bacteriofood could be used to produce and carry vital nutrients that can maintain a healthy human. Most useful in third world countries where food is hard to come around. Bacteria being easy to grow and maintain, could be a simple way to feed the underfed. Just trying to throw out any idea that comes across.



Revision as of 18:18, 9 April 2008


iGEM 2008

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  • So I guess that it might be helpful if we keep a running list of interesting ideas that we might randomly come across while thinking about syn. bio. Maybe we can move this to another page when it gets larger.
  • Using network motifs? Uri Alon has done some interesting stuff with it. Should we need to use time-delayed releases, might be handy. http://www.nature.com/nrg/journal/v8/n6/pdf/nrg2102.pdf
  • Using ribozymes? No idea where this is going or if its valid, but who said that we needed to follow how the cell does it.... perhaps RNAi or one of those unique forms could be used as a branching statement in what seems to be a rather linear DNA programming methodology (or at least from first glance).

... I'll format this (i.e. learn how to use wiki syntax) later I guess - Allen

Some ideas

Random Number Generator

  • FimE inverts a specific stretch of DNA, defined by a pair of sequence elements (IRR and IRL), forming a DNA loop between the two elements[3]. If we add multiple copies of one of these elements (one IRR, two IRL), would FimE randomly choose one of the sites (one IRL out of the pair) to invert between? Either choose one of several promoters to attach to a given gene, or one of several genes to attach to a given promoter.
  • Then, can we tune the probability (from, say, 60:40 to 80:20 to 20:80)? Ideally do this dynamically (based on some small molecule) - use proteins that bend DNA to affect the probability of loop formation.

Population Variability

  • Slipped-strand mispairing (SSM)[4] can produce a heritable variation in the expression from a promoter. Roughly one in 1000 divisions produces a change in expression. Couple this expression to a selectable/counterselectable marker. Under any given condition (selection, say), the population thrives, but with a small group of the opposite phenotype (non-expressing). Switch conditions (to counterselecting), and the population can use these revertants to recover. The switching is stochastic by nature and can be directly compared to both natural [5] and synthetic [6] systems that utilize stochastic switching to adapt to variable and fluctuating environments.
  • Under constantly varying conditions, most circuits would die. These cells, though, can adapt and pass that adaptation on to their descendants.

Differentiation

  • Or, combine the fimE and SSM mechanisms - have the SSM promoter express fimE. When you get a change in the SSM expression, fimE turns on and the cell irreversibly switches state (if the random number generator works, perhaps to one of several states). You maintain a population of undifferentiated (SSM-off) cells that continually sprout new differentiated ones (SSM-on, fimE-on).

Pimp my E. coli

  • We can trick out our E. coli similar to our car -- spinners, rims, spoilers, etc. One of many modifications is have the cells express reflectins on their surface. Reflectins are highly reflective proteins only found in squid reflective tissue [7]. Other ideas?

A more analog device

  • Digital and analog responses, a common feature of electrical circuits, are also displayed by biological networks. While recent research has focused on engineering a more digital response using cooperativity or transcriptional cascades, we go the other way and engineer a more analog device.
  • One way to do this is to express mutiple tetR variants that have different affinities for aTc, the primary inducer used in bacteria. I have found one paper that reports tetR variants with different affinities [8], although I'm sure more can be tracked down.

Bacteriofood

  • After reviewing UC Berkeley's BactoBlood in the 2007 iGEM Jamboree, Bacteriofood could be used to produce and carry vital nutrients that can maintain a healthy human. Most useful in third world countries where food is hard to come around. Bacteria being easy to grow and maintain, could be a simple way to feed the underfed. Just trying to throw out any idea that comes across.

CO2 Bacteria

  • It seems many researchers are looking to find or develop a biofuel that can sustain our cars, planes, machines, etc. As time passes by, we are still polluting our atmosphere with greenhouse gases, so why not develop a bacteria that will *chew up* or turn CO2 into a less harmful substance. (Is there any bacteria that consumes CO2?) Maybe we could create filters of bacteria to be put along our car exhausts, etc. I don't have much knowledge about greenhouse gases, but just an idea to throw out.

References

  1. Win MN and Smolke CD. A modular and extensible RNA-based gene-regulatory platform for engineering cellular function. Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14283-8. DOI:10.1073/pnas.0703961104 | PubMed ID:17709748 | HubMed [win]
  2. An CI, Trinh VB, and Yokobayashi Y. Artificial control of gene expression in mammalian cells by modulating RNA interference through aptamer-small molecule interaction. RNA. 2006 May;12(5):710-6. DOI:10.1261/rna.2299306 | PubMed ID:16606868 | HubMed [an]
  3. Ham TS, Lee SK, Keasling JD, and Arkin AP. A tightly regulated inducible expression system utilizing the fim inversion recombination switch. Biotechnol Bioeng. 2006 May 5;94(1):1-4. DOI:10.1002/bit.20916 | PubMed ID:16534780 | HubMed [fim]
  4. Torres-Cruz J and van der Woude MW. Slipped-strand mispairing can function as a phase variation mechanism in Escherichia coli. J Bacteriol. 2003 Dec;185(23):6990-4. DOI:10.1128/JB.185.23.6990-6994.2003 | PubMed ID:14617664 | HubMed [phase]
  5. Süel GM, Garcia-Ojalvo J, Liberman LM, and Elowitz MB. An excitable gene regulatory circuit induces transient cellular differentiation. Nature. 2006 Mar 23;440(7083):545-50. DOI:10.1038/nature04588 | PubMed ID:16554821 | HubMed [fluct1]
  6. Acar M, Mettetal JT, and van Oudenaarden A. Stochastic switching as a survival strategy in fluctuating environments. Nat Genet. 2008 Apr;40(4):471-5. DOI:10.1038/ng.110 | PubMed ID:18362885 | HubMed [fluct2]
  7. Crookes WJ, Ding LL, Huang QL, Kimbell JR, Horwitz J, and McFall-Ngai MJ. Reflectins: the unusual proteins of squid reflective tissues. Science. 2004 Jan 9;303(5655):235-8. DOI:10.1126/science.1091288 | PubMed ID:14716016 | HubMed [reflect]
  8. Kintrup M, Schubert P, Kunz M, Chabbert M, Alberti P, Bombarda E, Schneider S, and Hillen W. Trp scanning analysis of Tet repressor reveals conformational changes associated with operator and anhydrotetracycline binding. Eur J Biochem. 2000 Feb;267(3):821-9. DOI:10.1046/j.1432-1327.2000.01063.x | PubMed ID:10651820 | HubMed [tetR]
All Medline abstracts: PubMed | HubMed