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首页> 外文会议>2014 40th Annual Northeast Bioengineering Conference >First passage time stochasticity in a gene network with feedback regulation
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First passage time stochasticity in a gene network with feedback regulation

机译：具有反馈调节的基因网络中的首次通过时间随机性

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摘要

The inherent probabilistic nature of the biochemical reactions, and low copy number of species can lead to stochasticity in gene expression across identical cells. Interestingly, this would lead to stochasticity in the event timing as well. We investigate a gene expression model for stochasticity in event timing, specifically the events that occur when a critical protein threshold is achieved for the first time, called the first passage time (FPT). We first consider an unregulated gene expression model, and examine the conditions under which stochasticity in FPT will be minimum, given a fixed threshold and mean of FPT. We find that stochasticity in FPT decreases with a decrease in mean burst size (number of proteins produced from an mRNA before it degrades) in the gene expression. Further, we study effect of feedback regulation of transcription rate, a regulation motif known to affect stochasticity in gene expression, on the stochasticity of FPT. Our analysis reveals that such a regulation would rather result into higher stochasticity of FPT as compared with no regulation case. We relate the results obtained with time taken by λ phage-infected E. coli cells to lyse and infer the regulatory motif responsible for preciseness of the lysis time.
机译：生化反应的固有概率性质以及物种的低拷贝数可导致同一细胞中基因表达的随机性。有趣的是，这也会导致事件计时的随机性。我们调查随机事件发生时间的基因表达模型，特别是首次达到关键蛋白质阈值（称为第一次通过时间（FPT））时发生的事件。我们首先考虑一个不受调节的基因表达模型，并研究在给定固定阈值和FPT平均值的情况下FPT随机性最小的条件。我们发现，FPT的随机性随基因表达中平均突发大小（mRNA降解之前从mRNA产生的蛋白质数量）的减少而降低。此外，我们研究了转录速率的反馈调节（一种已知会影响基因表达的随机性的调节基序）对FPT随机性的影响。我们的分析表明，与没有法规的情况相比，这样的法规宁可导致FPT的随机性更高。我们将获得的结果与λ噬菌体感染的大肠杆菌细胞裂解和推断负责裂解时间精确度的调控基序相关联。

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