Cellular design principles

Biomolecular control for predictable performance

I’m interested in new circuit design guided by mathematical models to improve biomolecular control in bacterial cells. While many genetic parts and circuits have been made, there are still many elements that we still don’t understand when building more complex circuits. I believe by coupling well characterized circuits with modeling we can gain insights into how to improve circuits and how natural genetic circuits behave.

Adapted from “Control theory meets synthetic biology”

One project on compositional context looked into how the expression of a gene can affect its neighbors through supercoiling of DNA. By modeling the effect in cell-free expression and in E. coli, we were able to build a dynamical model that showed us a genetic toggle switch convergent orientation should perform better than in divergent orientation like the original. We then showed that the convergent toggle switch is in fact more stable.

A current project focuses on resource sharing of dCas9 when multiple guide RNAs are expressed in a CRISPRi or CRISPRa system. We hope to use riboregulators to build a resource allocator that improves the scaling properties of CRISPRi circuits.

 

Relevant publications:

E. Yeung, A. J. Dy , K. B. Martin, A. H. Ng, D. Del Vecchio, J. L. Beck, J. J. Collins, and R. M. Murray. “The Effect of Compositional Context on Synthetic Gene Networks.” Cell Systems 5 (2017): 11–24 (pdf)

D. Del Vecchio, A. J. Dy , and Y. Qian. “Control theory meets synthetic biology.” Journal of The Royal Society Interface 13.120 (2016): 20160380. [review] (pdf)