Programmable Fusion and Differentiation of Synthetic Minimal Cells

Nathaniel J. Gaut; Jose Gomez-Garcia; Joseph M Heili; Brock W Cash; Qiyuan Han; Aaron E. Engelhart; Katarzyna P. Adamala

doi:10.1021/acssynbio.1c00519

Programmable Fusion and Differentiation of Synthetic Minimal Cells

Nathaniel J. Gaut, Jose Gomez-Garcia, Joseph M Heili, Brock W Cash, Qiyuan Han, Aaron E. Engelhart, Katarzyna P. Adamala

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Synthetic cells can mimic the intricate complexities of live cells, while mitigating the level of noise that is present natural systems; however, many crucial processes still need to be demonstrated in synthetic cells to use them to comprehensively study and engineer biology. Here we demonstrate key functionalities of synthetic cells previously available only to natural life: differentiation and mating. This work presents a toolset for engineering combinatorial genetic circuits in synthetic cells. We demonstrate how progenitor populations can differentiate into new lineages in response to small molecule stimuli or as a result of fusion, and we provide practical demonstration of utility for metabolic engineering. This work provides a tool for bioengineering and for natural pathway studies, as well as paving the way toward the construction of live artificial cells.

Original language	English (US)
Pages (from-to)	855-866
Number of pages	12
Journal	ACS Synthetic Biology
Volume	11
Issue number	2
DOIs	https://doi.org/10.1021/acssynbio.1c00519
State	Published - Feb 18 2022

Bibliographical note

Funding Information:
This work was supported by generous gifts from Jeremy Wertheimer, the Hackett Royalty Fund award, NIH 5R01MH114031-02, NSF 1840301, NASA CON00000065217, Semiconductor Research Corporation 2018-SB-2837-C, and John Templeton Foundation Exploring the Informational Transitions Bridging Inorganic Chemistry and Minimal Life awards.

Publisher Copyright:
© 2022 American Chemical Society

Keywords

TxTl
artificial life
cell-free
genetic circuit
liposome
synthetic cell

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

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abstract = "Synthetic cells can mimic the intricate complexities of live cells, while mitigating the level of noise that is present natural systems; however, many crucial processes still need to be demonstrated in synthetic cells to use them to comprehensively study and engineer biology. Here we demonstrate key functionalities of synthetic cells previously available only to natural life: differentiation and mating. This work presents a toolset for engineering combinatorial genetic circuits in synthetic cells. We demonstrate how progenitor populations can differentiate into new lineages in response to small molecule stimuli or as a result of fusion, and we provide practical demonstration of utility for metabolic engineering. This work provides a tool for bioengineering and for natural pathway studies, as well as paving the way toward the construction of live artificial cells.",

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AU - Gomez-Garcia, Jose

AU - Heili, Joseph M

AU - Cash, Brock W

AU - Han, Qiyuan

AU - Engelhart, Aaron E.

AU - Adamala, Katarzyna P.

N1 - Funding Information: This work was supported by generous gifts from Jeremy Wertheimer, the Hackett Royalty Fund award, NIH 5R01MH114031-02, NSF 1840301, NASA CON00000065217, Semiconductor Research Corporation 2018-SB-2837-C, and John Templeton Foundation Exploring the Informational Transitions Bridging Inorganic Chemistry and Minimal Life awards. Publisher Copyright: © 2022 American Chemical Society

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N2 - Synthetic cells can mimic the intricate complexities of live cells, while mitigating the level of noise that is present natural systems; however, many crucial processes still need to be demonstrated in synthetic cells to use them to comprehensively study and engineer biology. Here we demonstrate key functionalities of synthetic cells previously available only to natural life: differentiation and mating. This work presents a toolset for engineering combinatorial genetic circuits in synthetic cells. We demonstrate how progenitor populations can differentiate into new lineages in response to small molecule stimuli or as a result of fusion, and we provide practical demonstration of utility for metabolic engineering. This work provides a tool for bioengineering and for natural pathway studies, as well as paving the way toward the construction of live artificial cells.

AB - Synthetic cells can mimic the intricate complexities of live cells, while mitigating the level of noise that is present natural systems; however, many crucial processes still need to be demonstrated in synthetic cells to use them to comprehensively study and engineer biology. Here we demonstrate key functionalities of synthetic cells previously available only to natural life: differentiation and mating. This work presents a toolset for engineering combinatorial genetic circuits in synthetic cells. We demonstrate how progenitor populations can differentiate into new lineages in response to small molecule stimuli or as a result of fusion, and we provide practical demonstration of utility for metabolic engineering. This work provides a tool for bioengineering and for natural pathway studies, as well as paving the way toward the construction of live artificial cells.

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KW - cell-free

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KW - liposome

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Programmable Fusion and Differentiation of Synthetic Minimal Cells

Abstract

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Keywords

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