Engineering genetic circuit interactions within and between synthetic minimal cells

Katarzyna P. Adamala, Daniel A. Martin-Alarcon, Katriona R. Guthrie-Honea, Edward S. Boyden

Research output: Contribution to journalArticlepeer-review

239 Scopus citations

Abstract

Genetic circuits and reaction cascades are of great importance for synthetic biology, biochemistry and bioengineering. An open question is how to maximize the modularity of their design to enable the integration of different reaction networks and to optimize their scalability and flexibility. One option is encapsulation within liposomes, which enables chemical reactions to proceed in well-isolated environments. Here we adapt liposome encapsulation to enable the modular, controlled compartmentalization of genetic circuits and cascades. We demonstrate that it is possible to engineer genetic circuit-containing synthetic minimal cells (synells) to contain multiple-part genetic cascades, and that these cascades can be controlled by external signals as well as inter-liposomal communication without crosstalk. We also show that liposomes that contain different cascades can be fused in a controlled way so that the products of incompatible reactions can be brought together. Synells thus enable a more modular creation of synthetic biology cascades, an essential step towards their ultimate programmability.

Original languageEnglish (US)
Pages (from-to)431-439
Number of pages9
JournalNature Chemistry
Volume9
Issue number5
DOIs
StatePublished - May 1 2017

Bibliographical note

Funding Information:
National Institutes of Health (NIH) 1U01MH106011, Jeremy and JoyceWertheimer, NIH 1RM1HG008525, the Picower Institute Innovation Fund, NIH 1R01MH103910, NIH 1R01NS075421

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