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Feedback control promotes synchronisation of the cell-cycle across a population of yeast cells

Perrino, Giansimone; Fiore, Davide; Napolitano, Sara; Galdi, Francesca; La Regina, Antonella; di Bernardo, Mario; di Bernardo, Diego


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{
  "DOI": "10.1101/590844", 
  "author": [
    {
      "family": "Perrino, Giansimone"
    }, 
    {
      "family": "Fiore, Davide"
    }, 
    {
      "family": "Napolitano, Sara"
    }, 
    {
      "family": "Galdi, Francesca"
    }, 
    {
      "family": "La Regina, Antonella"
    }, 
    {
      "family": "di Bernardo, Mario"
    }, 
    {
      "family": "di Bernardo, Diego"
    }
  ], 
  "issued": {
    "date-parts": [
      [
        2019, 
        3, 
        27
      ]
    ]
  }, 
  "abstract": "<p>&nbsp;</p>\n\n<p>Abstract</p>\n\n<p>The periodic process of cell replication by division, known as cell-cycle, is a natural phenomenon occurring asynchronously in any cell population. Here, we consider the problem of synchronising cell-cycles across a population of yeast cells grown in a microfluidics device. Cells were engineered to reset their cell-cycle in response to low methionine levels. Automated syringes enable changing methionine levels (control input) in the microfluidics device. However, the control input resets only those cells that are in a specific phase of the cell-cycle (G1 phase), while the others continue to cycle unperturbed. We devised a simplified dynamical model of the cell-cycle, inferred its parameters from experimental data and then designed two control strategies: (i) an open-loop controller based on the application of periodic stimuli; (ii) a closed-loop model predictive controller (MPC) that selects the sequence of control stimuli which maximises a synchronisation index. Both the proposed control strategies were validated in-silico, together with experimental validation of the open-loop strategy.</p>", 
  "title": "Feedback control promotes synchronisation of the cell-cycle across a population of yeast cells", 
  "type": "article", 
  "id": "4835897"
}
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