IGEM:Harvard/2006/Brainstorming Papers - Jeffrey

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 |
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 |

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