Using noise to control heterogeneity of isogenic populations in homogenous environments.
Using noise to control heterogeneity of isogenic populations in homogenous environments.
复制标题
使用噪声来控制同质环境中同基因群体的异质性。
DOI：
10.1088/1478-3975/12/4/045003
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发表时间：
2015
期刊：
影响因子：
2
通讯作者：
Munsky,Brian
中科院分区：
文献类型：
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作者：
Szymańska,Paulina;Gritti,Nicola;Keegstra,JohannesM;Soltani,Mohammad;Munsky,Brian
我们探索在何种程度上的个人，遗传相同的细胞的表型可以相互独立地控制，只使用一个单一的同质环境输入。我们表明，这种控制理论上是不可能的，如果限制在一个确定性的设置，但它可以很容易地实现，如果一个利用在单细胞水平上引入的异质性，由于基因调控的随机波动。使用随机分析的遗传学的拨动开关，我们开发了一种控制策略，最大限度地提高的机会，一个选定的细胞将表达一种表型，而其余的表达另一种。控制机制使用紫外线辐射来增强所有细胞中相同的蛋白质降解。只有通过监测随机蛋白质波动并在有利的时间和水平应用UV控制才有可能控制单个细胞。对于两个相同的细胞，我们的随机控制律可以驱动所选细胞的蛋白质表达高于其邻居，成功率超过99%。在30个相同细胞的群体中，我们可以驱动给定细胞始终保持在前20%内。虽然细胞噪声通常会损害生物反应的可预测性，但我们的研究结果表明，它也可以同时提高这些相同反应的可控性。
We explore the extent to which the phenotypes of individual, genetically identical cells can be controlled independently from each other using only a single homogeneous environmental input. We show that such control is theoretically impossible if restricted to a deterministic setting, but it can be achieved readily if one exploits heterogeneities introduced at the single-cell level due to stochastic fluctuations in gene regulation. Using stochastic analyses of a bistable genetic toggle switch, we develop a control strategy that maximizes the chances that a chosen cell will express one phenotype, while the rest express another. The control mechanism uses UV radiation to enhance identically protein degradation in all cells. Control of individual cells is made possible only by monitoring stochastic protein fluctuations and applying UV control at favorable times and levels. For two identical cells, our stochastic control law can drive protein expression of a chosen cell above its neighbor with a better than 99% success rate. In a population of 30 identical cells, we can drive a given cell to remain consistently within the top 20%. Although cellular noise typically impairs predictability for biological responses, our results show that it can also simultaneously improve controllability for those same responses.