Automatic synchronisation of the cell cycle in budding yeast through closed-loop feedback control

Giansimone Perrino, Sara Napolitano, Francesca Galdi, Antonella La Regina, Davide Fiore, Teresa Giuliano, Mario di Bernardo and Diego di Bernardo ()
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Giansimone Perrino: Telethon Institute of Genetics and Medicine (TIGEM)
Sara Napolitano: Telethon Institute of Genetics and Medicine (TIGEM)
Francesca Galdi: Telethon Institute of Genetics and Medicine (TIGEM)
Antonella La Regina: Telethon Institute of Genetics and Medicine (TIGEM)
Davide Fiore: University of Naples Federico II
Teresa Giuliano: Telethon Institute of Genetics and Medicine (TIGEM)
Mario di Bernardo: University of Naples Federico II
Diego di Bernardo: Telethon Institute of Genetics and Medicine (TIGEM)

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract The cell cycle is the process by which eukaryotic cells replicate. Yeast cells cycle asynchronously with each cell in the population budding at a different time. Although there are several experimental approaches to synchronise cells, these usually work only in the short-term. Here, we build a cyber-genetic system to achieve long-term synchronisation of the cell population, by interfacing genetically modified yeast cells with a computer by means of microfluidics to dynamically change medium, and a microscope to estimate cell cycle phases of individual cells. The computer implements a controller algorithm to decide when, and for how long, to change the growth medium to synchronise the cell-cycle across the population. Our work builds upon solid theoretical foundations provided by Control Engineering. In addition to providing an avenue for yeast cell cycle synchronisation, our work shows that control engineering can be used to automatically steer complex biological processes towards desired behaviours similarly to what is currently done with robots and autonomous vehicles.

Date: 2021
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DOI: 10.1038/s41467-021-22689-w

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