• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Systems-level analyses of osmoregulation in Saccharomyces cerevisiae.
【24h】

Systems-level analyses of osmoregulation in Saccharomyces cerevisiae.

机译：酿酒酵母中渗透调节的系统级分析。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Developing a predictive dynamic model of a biological system often requires that the system be extensively characterized genetically and biochemically. But, relatively few systems are sufficiently well characterized to be amenable to quantitative modeling. Here I present two studies in which my coworkers and I combine time-lapse microscopy of living single cells with tools from the engineering disciplines to model an endogenous stress-response system while exploiting few of the previously known system details. Our strategies are very general and highlight the promise of studying other biological systems in an analogous manner.;We investigate the frequency dependence of the osmotic-shock response in Saccharomyces cerevisiae, which is mediated largely by the MAP kinase Hog1. The activity of Hog1 correlates with its enrichment in the nucleus, and we monitor its localization while simultaneously applying salt pulses spanning a range of frequencies. Using linear systems theory and our frequency-response data alone, we derive a quantitative model of the system capable of predicting the Hog1 response to an arbitrary input. We further use system-identification techniques to recast our model into biologically interpretable equations, which correspond very highly with the known network structure. Our analysis suggests that the reactions dominating the stress response occur on a timescale shorter than that required for gene expression, even though minor stress elicits a transcriptional response. We find that gene expression plays a role in facilitating the response to future shocks.;We next explore how perfect adaptation is achieved in the system. The yeast osmoregulation system is a closed feedback loop, and extensive theoretical work from control engineering shows that only a special type of negative feedback, termed "integral feedback", can permit perfect adaptation. We determine the network location of the integrating reaction(s) responsible for this paramount system feature by utilizing small-molecule inhibitors, a range of salt inputs (e.g., steps and ramps), and theoretical arguments. We conclude that there is only one effective integrator in the system; it requires Hog1 kinase activity, and it regulates glycerol synthesis but not leakage.
机译：建立生物系统的预测动力学模型通常需要对该系统进行遗传和生化方面的广泛表征。但是，相对较少的系统具有足够好的特征以适合于定量建模。在这里，我进行了两项研究，其中，我和我的同事们将活的单细胞的延时显微镜与工程学领域的工具相结合，以对内源性应力响应系统进行建模，同时利用了一些先前已知的系统细节。我们的策略非常笼统，并突出了以类似方式研究其他生物系统的前景。；我们研究了酿酒酵母中渗透压休克反应的频率依赖性，其主要由MAP激酶Hog1介导。 Hog1的活性与其在细胞核中的富集相关，我们在同时施加跨越一定频率范围的盐脉冲的同时监测其定位。仅使用线性系统理论和我们的频率响应数据，我们便得出了能够预测任意输入的Hog1响应的系统定量模型。我们进一步使用系统识别技术，将我们的模型重铸为可生物解释的方程式，该方程式与已知的网络结构高度对应。我们的分析表明，主导应激反应的反应发生的时间比基因表达所需的时间短，尽管较小的应激引起转录反应。我们发现基因表达在促进对未来冲击的反应中起着作用。;我们接下来探索如何在系统中实现完美的适应。酵母渗透调节系统是一个封闭的反馈回路，控制工程的大量理论工作表明，只有一种特殊类型的负反馈（称为“积分反馈”）才能实现完美的适应。我们通过利用小分子抑制剂，一定范围的盐输入（例如，阶跃和斜率）以及理论论据来确定负责该最重要系统特征的积分反应的网络位置。我们得出的结论是，系统中只有一个有效的积分器。它需要Hog1激酶活性，并调节甘油合成，但不调节泄漏。

著录项

  • 作者

    Muzzey, Dale Edward.;

  • 作者单位

    Harvard University.;

  • 授予单位 Harvard University.;
  • 学科 Biophysics General.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 202 p.
  • 总页数 202
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

  • 入库时间 2022-08-17 11:38:25

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号