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通过闭环反馈控制自动同步出芽酵母中的细胞周期。

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

机构信息

Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.

Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Naples, Italy.

出版信息

Nat Commun. 2021 Apr 27;12(1):2452. doi: 10.1038/s41467-021-22689-w.

DOI:10.1038/s41467-021-22689-w
PMID:33907191
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8079375/
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.

摘要

细胞周期是真核细胞复制的过程。酵母细胞以不同的时间进行出芽的方式进行异步循环。尽管有几种实验方法可以使细胞同步,但这些方法通常只能在短期内起作用。在这里,我们构建了一个基于网络的遗传系统,通过微流控技术将遗传修饰的酵母细胞与计算机接口,动态改变培养基,并通过显微镜估计单个细胞的细胞周期阶段,从而实现细胞群体的长期同步。计算机实施控制器算法来决定何时以及多长时间改变生长培养基,以使整个群体的细胞周期同步。我们的工作建立在控制工程提供的坚实理论基础之上。除了为酵母细胞周期同步提供途径之外,我们的工作还表明,控制工程可用于自动引导复杂的生物过程朝着所需的行为发展,类似于目前对机器人和自动驾驶车辆所做的那样。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4187/8079375/73a253f70bac/41467_2021_22689_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4187/8079375/4e1fd657e591/41467_2021_22689_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4187/8079375/2860a4abf62e/41467_2021_22689_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4187/8079375/fe00ac974b09/41467_2021_22689_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4187/8079375/73a253f70bac/41467_2021_22689_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4187/8079375/4e1fd657e591/41467_2021_22689_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4187/8079375/2860a4abf62e/41467_2021_22689_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4187/8079375/fe00ac974b09/41467_2021_22689_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4187/8079375/73a253f70bac/41467_2021_22689_Fig4_HTML.jpg

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