SURF 2012: Design and construction of novel synthetic biochemical switches

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2012 SURF project description

  • Mentor: Richard Murray
  • Co-mentor: Dan Siegal-Gaskins

Bistability--a property of systems that can exist in either of two stable steady states--is ubiquitous across the biological sciences. Even simple biological systems such as viruses and cells possess the ability to regulate essential processes in a switch-like, "on/off" manner. The study of how these biochemical switches function continues to grow as an active and exciting area of research, right along with the search for and development of new switches.

We adopt an interdisciplinary approach that combines traditional experimental biology with techniques from the world of engineering and mathematics to better understand biochemical bistability and further explore its biotechnological potential. This project will build on recent theoretical work on bistability in simple networks consisting of only two protein-coding genes. Students will generate detailed mathematical models of novel bistable circuits in order to explore the circuits’ operational regime and to elucidate the effect of network evolution on bistability. The models will serve as the basis for synthetic construction of these never-before-seen switches. Successful completion of this project will lead to a dramatic increase in the number of bistable circuits available to the synthetic biology community and highlight the value of predictive modeling to the modern biological sciences.

References

  1. D. Siegal-Gaskins, E. Grotewold and G. D. Smith, The capacity for multistability in small gene regulatory networks. BMC Systems Biology, 3:96, 2009
  2. D. Siegal-Gaskins, M. K. Mejia-Guerra, G. D. Smith and E. Grotewold, Emergence of Switch-Like Behavior in a Large Family of Simple Biochemical Networks. PLoS Comput Biol 7(5), 2011.