Kannoly Sherin, Gao Tianhui, Dey Supravat, Wang Ing-Nang, Singh Abhyudai, Dennehy John J
Biology Department, Queens College of The City University of New York, Queens, NY, USA.
Department of Electrical and Computer Engineering, University of Delaware, Newark, DE, USA.
iScience. 2020 Jun 26;23(6):101186. doi: 10.1016/j.isci.2020.101186. Epub 2020 May 21.
How the noisy expression of regulatory proteins affects timing of intracellular events is an intriguing fundamental problem that influences diverse cellular processes. Here we use the bacteriophage λ to study event timing in individual cells where cell lysis is the result of expression and accumulation of a single protein (holin) in the Escherichia coli cell membrane up to a critical threshold level. Site-directed mutagenesis of the holin gene generated phage variants that vary in their lysis times from 30 to 190 min. Observation of the lysis times of single cells reveals an intriguing finding-the noise in lysis timing first decreases with increasing lysis time to reach a minimum and then sharply increases at longer lysis times. A mathematical model with stochastic expression of holin together with dilution from cell growth was sufficient to explain the non-monotonic noise profile and identify holin accumulation thresholds that generate precision in lysis timing.
调节蛋白的噪声表达如何影响细胞内事件的时间安排是一个有趣的基本问题，它影响着多种细胞过程。在这里，我们使用噬菌体λ来研究单个细胞中的事件时间安排，在这些细胞中，细胞裂解是由于大肠杆菌细胞膜中单一蛋白质（holin）表达并积累到临界阈值水平的结果。对holin基因进行定点诱变产生了裂解时间从30分钟到190分钟不等的噬菌体变体。对单个细胞裂解时间的观察揭示了一个有趣的发现——裂解时间的噪声首先随着裂解时间的增加而降低，达到最小值，然后在更长的裂解时间时急剧增加。一个包含holin随机表达以及细胞生长稀释的数学模型足以解释这种非单调的噪声分布，并确定在裂解时间上产生精确性的holin积累阈值。
