期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 45, 页码 E10797-E10806出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1810858115
关键词
temperature; cellular decision; noise; synthetic gene circuit; feedback regulation
资金
- Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship [PDF-453977-2014]
- NVIDIA Corporation Titan Xp GPU grant
- NIH National Research Service Award Fellowship [F31-GM101946]
- National Science Foundation Alliances for Graduate Education
- Professoriate-Transformation Fellowship [HRD-1311318]
- NIH/National Institute of General Medical Sciences Maximizing Investigators' Research Award [R35GM122561]
- Laufer Center for Physical and Quantitative Biology
Most organisms must cope with temperature changes. This involves genes and gene networks both as subjects and agents of cellular protection, creating difficulties in understanding. Here, we study how heating and cooling affect expression of single genes and synthetic gene circuits in Saccharomyces cerevisiae. We discovered that nonoptimal temperatures induce a cell fate choice between stress resistance and growth arrest. This creates dramatic gene expression bimodality in isogenic cell populations, as arrest abolishes gene expression. Multiscale models incorporating population dynamics, temperature-dependent growth rates, and Arrhenius scaling of reaction rates captured the effects of cooling, but not those of heating in resistant cells. Molecular-dynamics simulations revealed how heating alters the conformational dynamics of the TetR repressor, fully explaining the experimental observations. Overall, nonoptimal temperatures induce a cell fate decision and corrupt gene and gene network function in computationally predictable ways, which may aid future applications of engineered microbes in nonstandard temperatures.
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