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Programmable synthetic biomolecular condensates for cellular control.

Publication ,  Journal Article
Dai, Y; Farag, M; Lee, D; Zeng, X; Kim, K; Son, H-I; Guo, X; Su, J; Peterson, N; Mohammed, J; Ney, M; Shapiro, DM; Pappu, RV; Chilkoti, A; You, L
Published in: Nature chemical biology
April 2023

The formation of biomolecular condensates mediated by a coupling of associative and segregative phase transitions plays a critical role in controlling diverse cellular functions in nature. This has inspired the use of phase transitions to design synthetic systems. While design rules of phase transitions have been established for many synthetic intrinsically disordered proteins, most efforts have focused on investigating their phase behaviors in a test tube. Here, we present a rational engineering approach to program the formation and physical properties of synthetic condensates to achieve intended cellular functions. We demonstrate this approach through targeted plasmid sequestration and transcription regulation in bacteria and modulation of a protein circuit in mammalian cells. Our approach lays the foundation for engineering designer condensates for synthetic biology applications.

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Published In

Nature chemical biology

DOI

EISSN

1552-4469

ISSN

1552-4450

Publication Date

April 2023

Volume

19

Issue

4

Start / End Page

518 / 528

Related Subject Headings

  • Organelles
  • Mammals
  • Intrinsically Disordered Proteins
  • Biomolecular Condensates
  • Biochemistry & Molecular Biology
  • Animals
  • 3404 Medicinal and biomolecular chemistry
  • 3101 Biochemistry and cell biology
  • 0601 Biochemistry and Cell Biology
  • 0304 Medicinal and Biomolecular Chemistry
 

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Dai, Y., Farag, M., Lee, D., Zeng, X., Kim, K., Son, H.-I., … You, L. (2023). Programmable synthetic biomolecular condensates for cellular control. Nature Chemical Biology, 19(4), 518–528. https://doi.org/10.1038/s41589-022-01252-8
Dai, Yifan, Mina Farag, Dongheon Lee, Xiangze Zeng, Kyeri Kim, Hye-In Son, Xiao Guo, et al. “Programmable synthetic biomolecular condensates for cellular control.Nature Chemical Biology 19, no. 4 (April 2023): 518–28. https://doi.org/10.1038/s41589-022-01252-8.
Dai Y, Farag M, Lee D, Zeng X, Kim K, Son H-I, et al. Programmable synthetic biomolecular condensates for cellular control. Nature chemical biology. 2023 Apr;19(4):518–28.
Dai, Yifan, et al. “Programmable synthetic biomolecular condensates for cellular control.Nature Chemical Biology, vol. 19, no. 4, Apr. 2023, pp. 518–28. Epmc, doi:10.1038/s41589-022-01252-8.
Dai Y, Farag M, Lee D, Zeng X, Kim K, Son H-I, Guo X, Su J, Peterson N, Mohammed J, Ney M, Shapiro DM, Pappu RV, Chilkoti A, You L. Programmable synthetic biomolecular condensates for cellular control. Nature chemical biology. 2023 Apr;19(4):518–528.

Published In

Nature chemical biology

DOI

EISSN

1552-4469

ISSN

1552-4450

Publication Date

April 2023

Volume

19

Issue

4

Start / End Page

518 / 528

Related Subject Headings

  • Organelles
  • Mammals
  • Intrinsically Disordered Proteins
  • Biomolecular Condensates
  • Biochemistry & Molecular Biology
  • Animals
  • 3404 Medicinal and biomolecular chemistry
  • 3101 Biochemistry and cell biology
  • 0601 Biochemistry and Cell Biology
  • 0304 Medicinal and Biomolecular Chemistry