A synthetic circuit for selectively arresting daughter cells to create aging populations

Afonso, Bruno; Silver, Pamela A.; Ajo-Franklin, Caroline M.

doi:10.1093/nar/gkq075

Title: A synthetic circuit for selectively arresting daughter cells to create aging populations

Journal Article · 11 February 2010 · Nucleic Acids Research

DOI: https://doi.org/10.1093/nar/gkq075 · OSTI ID:1625470

Afonso, Bruno ^[1]; Silver, Pamela A. ^[2]; Ajo-Franklin, Caroline M. ^[3]

Harvard Medical School, Boston, MA (United States). Dept. of Systems Biology; DOE/OSTI
Harvard Medical School, Boston, MA (United States). Dept. of Systems Biology
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

The ability to engineer genetic programs governing cell fate will permit new safeguards for engineered organisms and will further the biological understanding of differentiation and aging. Here, we have designed, built and implemented a genetic device in the budding yeast Saccharomyces cerevisiae that controls cell-cycle progression selectively in daughter cells. The synthetic device was built in a modular fashion by combining timing elements that are coupled to the cell cycle, i.e. cell-cycle specific promoters and protein degradation domains, and an enzymatic domain which conditionally confers cell arrest. Thus, in the presence of a drug, the device is designed to arrest growth of only newly-divided daughter cells in the population. Indeed, while the engineered cells grow normally in the absence of drug, with the drug the engineered cells display reduced, linear growth on the population level. Fluorescence microscopy of single cells shows that the device induces cell arrest exclusively in daughter cells and radically shifts the age distribution of the resulting population towards older cells. This device, termed the ‘daughter arrester’, provides a blueprint for more advanced devices that mimic developmental processes by having control over cell growth and death.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1625470

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 8 Vol. 38; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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Construction of synthetic regulatory networks in yeast Blount, Benjamin A.; Weenink, Tim; Ellis, Tom FEBS Letters, Vol. 586, Issue 15 https://doi.org/10.1016/j.febslet.2012.01.053	journal	February 2012
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Introduction of customized inserts for streamlined assembly and optimization of BioBrick synthetic genetic circuits Norville, Julie E.; Derda, Ratmir; Gupta, Saurabh Journal of Biological Engineering, Vol. 4, Issue 1 https://doi.org/10.1186/1754-1611-4-17	journal	December 2010
Construction of hybrid regulated mother-specific yeast promoters for inducible differential gene expression Pothoulakis, Georgios; Ellis, Tom PLOS ONE, Vol. 13, Issue 3 https://doi.org/10.1371/journal.pone.0194588	journal	March 2018
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The development and characterization of synthetic minimal yeast promoters Redden, Heidi; Alper, Hal S. Nature Communications, Vol. 6, Issue 1 https://doi.org/10.1038/ncomms8810	journal	July 2015
Introduction of customized inserts for streamlined assembly and optimization of BioBrick synthetic genetic circuits Norville, Julie E.; Derda, Ratmir; Gupta, Saurabh Journal of Biological Engineering, Vol. 4, Issue 1 https://doi.org/10.1186/1754-1611-4-17	journal	December 2010
Construction of hybrid regulated mother-specific yeast promoters for inducible differential gene expression Pothoulakis, Georgios; Ellis, Tom PLOS ONE, Vol. 13, Issue 3 https://doi.org/10.1371/journal.pone.0194588	journal	March 2018

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