RESEARCH - DIGITAL
The digital computing paradigm investigates how treating the presence or absence of proteins or small molecules in genetic circuits can emulate the digital logic abstraction in electronics where the presence or absence of voltages can be used to perform Boolean logic. This logic can be constructed to make “yes” and “no” decisions in response to external signals in the environment for bioremediation, biosensing, and biotherapeutics.
If the digital abstraction can be applied to genetic circuits, an entire discipline from electrical and computer engineering can be leveraged including software tools and design methodologies.
This project examines how transcriptional regulation in genetic circuits can replicate Boolean algebraic functionality. Gate connection is simplified by defining the input and output signals as RNA polymerase (RNAP) fluxes. Networks of genetic NOR gates can then be composed to create more complex functionality. Specifically, this project will build on this work to explore how the concepts used in this area toward combinational logic can be expanded to explore sequential logic.
Recombinase based digital logic can be realized by the addition of specific enzyme recognition sites in collections of DNA circuits made from well positioned parts. The placement of these recombinases allows for reconfiguration of generic “template” circuits into circuits with specific functionality. This project will expand on this work to create better performing and more complex circuits using this methodology.
A. A. K. Nielsen, B. S. Der, J. Shin, P. Vaidyanathan, V. Paralanov, E. A. Strychalski, D. Ross, D. Densmore, and C. A. Voigt, “Genetic circuit design automation,” Science, vol. 352, iss. 6281, 2016.
J. R. Rubens, G. Selvaggio, T. K. Lu, “Synthetic mixed-signal computation in living cells,” Nature Communications, vol. 7, article 11658, June 3, 2016.
N. Roehner and D. Densmore, "How to remember and revisit genetic designs automatically," 2016.
N. Roehner, E. M. Young, C. A. Voigt, B. D. Gordon, and D. Densmore, “Double dutch: a tool for designing combinatorial libraries of biological Systems,” ACS Synthetic biology, 2016.
N. Roquet, A. P. Soleimany, A. C. Ferris, S. Aaronson, T. K. Lu, “Synthetic Recombinase-Based State Machines in Living Cells,” Science, vol. 353, no. 6297, July 22, 2016.
P. Vaidyanathan, B. S. Der, S. Bhatia, N. Roehner, R. Silva, C. A. Voigt, and D. Densmore, “A Framework for Genetic Logic Synthesis,” Proceedings of the IEEE, vol. 103, iss. 11, pp. 2196-2207, 2015.
S. Bhatia, C. LaBoda, V. Yanez, T. Haddock-Angelli, and D. Densmore, "Permutation Machines," ACS Synthetic Biology, vol. 5, iss. 8, 2016.