Molecular Characterization of Target Scheduling in Bacterial

在这个项目中，研究人员和他们的学生正在努力更好地了解活着的有机体如何对环境做出反应。确定外界刺激如何影响细胞如何执行维持生命的新陈代谢功能是一个主要的兴趣。该项目旨在提供有关生命系统在暴露于可能导致不健康状态的不同外部压力时如何反应以维持正常的“健康”生存模式的基本机械知识。这些研究将支持对两名研究生和三名本科生进行跨学科培训，其中包括从少数族裔服务机构招聘的本科生。该项目还将通过现有的“培养未来的科学家”方案，向低收入、代表性不足的社区提供支持。在该方案中，中学生和他们的家人参观研究实验室，了解科学和工程知识，并在定期的“科学和电影”活动中向科学教师和学生提供支持。环境胁迫反应的一个重要特征是它们是由高度动态的网络介导的。对于全球RNA-蛋白质网络在应激后同时调节多条代谢途径的机制而言，这一点尤其正确。鉴于越来越多的发现表明了不同的靶标选择性，该项目试图确定导致特定基因亚组在特定时间或特定应激之后的不同调控的分子特征。该项目将应用一种新的方法，利用最近开发的体内分子表征工具和定量建模方法，以碳储存调控网络为模型系统：(I)建立在不同压力下差异调控的靶网络，(Ii)表征受该途径差异调控的不同靶点的分子特征，以及(Iii)通过正式的网络分析建立全球调控的功能相关性。这项工作侧重于CSR途径在应激后显著差异调节的基因，并将有助于在分子水平上理解参与全球代谢调节的动态网络。这些研究将产生更广泛的影响，扩大目前合成基因控制方案的设计，并建立一个通用平台，研究全球监管者在其整个本地网络中的功能。该项目由分子和细胞生物科学部的系统和合成生物学项目资助。

In this project, researchers and their students are working to better understand how living organisms respond to their environments. Determining how external stimuli affect how cells perform the metabolic functions that sustain life is of major interest. This project aims to provide basic mechanistic knowledge about how living systems react to maintain normal "healthy" survival patterns while exposed to different external stresses that could lead to unhealthy states. These studies will support the interdisciplinary training of two graduate and three undergraduate students, including undergraduates recruited from a minority serving institution. This project will also support outreach to a low-income, underrepresented community through the existing "Raising Future Scientists" program, where middle school children and their families visit the research laboratory for an introduction to science and engineering, and to science teachers and students at regular "Science and a Movie" events. An important feature of environmental stress responses is that they are mediated by highly dynamic networks. This is particularly true concerning the mechanisms by which global RNA-protein networks regulate multiple metabolic pathways simultaneously post-stress. Given an increasing number of findings that suggest differential target selectivity, this project seeks to identify molecular features that lead to the differential regulation of specific gene subsets at a specific time or after a specific stress. The project will apply a novel approach that employs recently developed in vivo molecular characterization tools and quantitative modeling approaches using the Carbon Storage Regulatory network as a model system to: (i) establish differentially regulated target networks under different stresses, (ii) characterize molecular features of different sets of targets that are differentially regulated by this pathway, and (iii) establish functional relevance of global regulation via formal network analysis. This work focuses on genes that are drastically differentially regulated post-stress by the Csr pathway and will contribute to understanding dynamic networks involved in global metabolic regulation at the molecular level. These studies will have the broader impact of expanding current designs of synthetic gene control schemes and of establishing a general platform for studying the function of global regulators in the context of their entire native networks. This project is funded by the Systems and Synthetic Biology Program in the Division of Molecular and Cellular Biosciences.