An engineered protein-phosphorylation toggle network with implications for endogenous network discovery

Author:

Mishra Deepak123ORCID,Bepler Tristan345ORCID,Teague Brian6ORCID,Berger Bonnie347ORCID,Broach Jim8ORCID,Weiss Ron12349ORCID

Affiliation:

1. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

2. Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA.

3. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.

4. Computational and Systems Biology Graduate Program, Massachusetts Institute of Technology, Cambridge, MA, USA.

5. Simons Machine Learning Center, New York Structural Biology Center, New York, NY, USA.

6. Department of Biology, University of Wisconsin, Stout, WI, USA.

7. Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA, USA.

8. Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, PA, USA.

9. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA.

Abstract

Building synthetic protein–based switches Synthetic circuits can potentially help to control complex biological processes, but systems based on regulating gene expression respond to stimuli at the minute to the hour time scale. Working in yeast cells, Mishra et al. report synthetic regulatory circuits based on protein phosphorylation reactions that respond to inputs within seconds (see the Perspective by Kholodenko and Okada). Multicomponent logic gates allowed ultrasensitive and stable switching between states. After validating their effective synthetic circuit, the authors searched known yeast protein interaction networks for similar regulatory motifs and found previously unrecognized circuits that function as native toggle switches in yeast. Science , aav0780, this issue p. eaav0780 ; see also abj5028, p. 25

Funder

National Science Foundation

National Institutes of Health

Army Research Office

Massachusetts Institute of Technology

Thomas and Stacey Siebel Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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