RT Journal Article
SR Electronic
T1 Using single-cell models to predict the functionality of synthetic circuits at the population scale
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.03.454887
DO 10.1101/2021.08.03.454887
A1 Chetan Aditya
A1 François Bertaux
A1 Gregory Batt
A1 Jakob Ruess
YR 2021
UL http://biorxiv.org/content/early/2021/08/04/2021.08.03.454887.abstract
AB Mathematical modeling has become a major tool to guide the characterization and synthetic construction of cellular processes. However, models typically lose their capacity to explain or predict experimental outcomes as soon as any, even minor, modification of the studied system or its operating conditions is implemented. This limits our capacity to fully comprehend the functioning of natural biological processes and is a major roadblock for the de novo design of complex synthetic circuits. Here, using a specifically constructed yeast optogenetic differentiation system as an example, we show that a simple deterministic model can explain system dynamics in given conditions but loses validity when modifications to the system are made. On the other hand, deploying theory from stochastic chemical kinetics and developing models of the system’s components that simultaneously track single-cell and population processes allows us to quantitatively predict emerging dynamics of the system without any adjustment of model parameters. We conclude that carefully characterizing the dynamics of cell-to-cell variability using appropriate modeling theory may allow one to unravel the complex interplay of stochastic single-cell and population processes and to predict the functionality of composed synthetic circuits in growing populations before the circuit is constructed.Competing Interest StatementThe authors have declared no competing interest.