Molecular Characterization of Interacting Bacterial Regulatory Networks

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Bacteria have networks of regulatory systems to facilitate survival in a variety of potentially harmful environments such as those containing low levels of essential nutrients or high levels of anti-bacterial agents. Ultimately, these regulatory systems allow bacteria to cope with damaging environments by mediating expression of stress-associated genes, which in turn make the bacteria more resistant. The long-term goal of this project is to better understand how stress-associated regulatory systems alter gene expression and promote bacterial resistance. This project focuses on two RNA binding proteins that are involved in post-transcriptional regulation and are part of different global stress response systems; the mechanisms of co-regulation by the RNA binding proteins and stress response pathways will be determined. This project will support the training of three undergraduates and the interdisciplinary training of two graduate students. This project will also facilitate broader outreach to a low-income underrepresented community through the existing "Raising Future Scientists" program and to a senior living center where public science talks will be given.Control of the decisions that are "computed" in cells in response to the environment is one of the main objectives of modern cellular and biomolecular engineering. Although an important feature of environmental stress responses is that they are mediated by dynamic "DNA decoding networks," understanding of the molecular mechanisms that regulate their coordination is in its infancy. For instance, two fundamental questions of global biological stress-response networks are: (i) how exclusive are target interactions amongst different regulators in the cell and, (ii) how do targets compete for regulators, particularly under different stresses? Moreover, is it is intriguing to think about: how could different interactions between a target and competing regulators change the fate (i.e. stability, degradation patterns etc.) of the target, particularly during stress? To get insight into these questions, the researchers propose to use the E. coli carbon storage (Csr) and the Hfq networks as model systems given their regulatory interactions, broad target scope, biological relevance and their mechanistic diversity. Specifically, the researchers propose to: (1) Characterize molecular regulatory features of dually recognized targets, and to (2) Establish the impact of dual regulatory function of the regulation of the dual targets via formal network analysis using a combination of traditional RNA-protein biochemistry methods as well as recent methods and tools developed by their research group involving high-throughput omics characterizations.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.