Molecular Characterization of Target Scheduling in Bacterial

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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.