IGEM:Harvard/2006/Brainstorming Papers - Jeffrey

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Self organization

  1. Basu S, Gerchman Y, Collins CH, Arnold FH, and Weiss R. A synthetic multicellular system for programmed pattern formation. Nature. 2005 Apr 28;434(7037):1130-4. DOI:10.1038/nature03461 | PubMed ID:15858574 | HubMed [so1]
  2. Basu S, Mehreja R, Thiberge S, Chen MT, and Weiss R. Spatiotemporal control of gene expression with pulse-generating networks. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6355-60. DOI:10.1073/pnas.0307571101 | PubMed ID:15096621 | HubMed [so2]
All Medline abstracts: PubMed | HubMed

A synthetic multicellular system for programmed pattern formation.

  • Basu et al. created a gene circuit with a non-monotonic response to AHL concentration.
  • Main idea: use two concentration boundaries to define three regions with different transcriptional activity
    • GFP is repressed at low and high concentrations of AHL, and expressed at medium concentrations
    • Basu et al. created three variants with different upper boundaries
      • Concentration varies with distance; thus, a mixture of different variants of bacteria produces a bullseye pattern when exposed to a point source of AHL
      • Multiple AHL sources produce pretty pictures
  • We could reuse the basic idea behind their circuit if we need to define a multiple-region response to some stimulus

Spatiotemporal control of gene expression with pulse-generating networks

  • Basu et al. created a gene circuit that exhibits transient expression of GFP in response to AHL ("pulse generator").
  • The amplitude and duration of this "pulse" can be artificially adjusted, and depend on the rate of increase of AHL concentration as well as the absolute concentration.
    • Cells can be made to respond to nearby cells and ignore far-away cells
      • Reporter expression varies with distance, even though AHL concentrations eventually reach the same level everywhere
  • Further tweaking:
    • Produce AHL as well as expressing GFP, to propagate the AHL signal
    • Connect the output of the pulse generator to a bistable switch