Multiscale Effects of Temperature on Synthetic Gene Circuits

Synthetic gene circuits are rationally designed gene networks that perform predefined functions, and have promising applications in many areas including agriculture, bioenergy, and biomedicine. However, synthetic gene circuits are built and characterized in laboratory settings where extracellular variables, such as temperature, are maintained at optimal levels. To study how nonoptimal temperatures (as in real-world conditions) affect the function of synthetic gene networks, we combined multiscale computational modeling with experiments in genetically engineered budding yeast Saccharomyces cerevisiae. We discovered that nonoptimal temperatures induce a cell fate choice between stress resistant and growth arrested phenotypes. Overall, we found that four key effects are required to fully predict the effect of nonoptimal temperatures across different biological scales: 1) cell fate choice between arrest and resistance, 2) slower growth rates, 3) Arrhenius dependence of reaction rates, and 4) changes in protein structure. These findings advance our understanding of how temperature affects living systems and enable more robust genetic engineering for real-world applications.

Charlebois et al., Proc. Natl. Acad. Sci., doi: 10.1073/pnas.1810858115, 2018.