Endy:Evolutionary stability project

This page will help coordinate the experimental/computational work being undertaken to improve the evolutionary stability of engineered biological systems. Read here for more background.

Project Outline

1. Evaluate and select several counter-selectable markers.
2. Evaluate a method for reliable long-term cell growth in E.Coli. These include:
   • Chemostat
   • Batch dilutions
3. Measure mutation rate of counter-selectable marker in long-term culture.
4. Develop an codon optimization algorithm for specifying a new DNA seq for the counter-selectable marker
   • Background research on the mechanisms by which cell spontaneiously mutate, the start of this can be found here.
5. Synthesize counter-selectable marker with "stabilized" sequence
6. Measure the mutation rate of the new marker.

Useful Resources

• E.Coli book chapter 18 (Mutagenesis)
• Schaaper, R. M. and R. L. Dunn (1991). "Spontaneous mutation in the Escherichia coli lacI gene." Genetics 129(2): 317-26.
  • Jasonk 21:40, 15 March 2006 (EST):Example of a characterization of the "mutation spectra" for a gene.

References

• Cell density regulation circuit lost function in ~70hrs in a 50ml chemostat culture

1. You L, Cox RS 3rd, Weiss R, and Arnold FH. Programmed population control by cell-cell communication and regulated killing. Nature. 2004 Apr 22;428(6985):868-71. DOI:10.1038/nature02491 |