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Reverse Engineering of RNA Regulatory Networks

Abstract

Understanding gene regulation is of central importance to biology because controlling when, where, and how genes are expressed accounts for a large proportion of the complexity and organization of living systems. While for many years RNA was largely thought of as the middleman for converting genetic information into biochemically active proteins, it has become increasingly clear that RNAs are also major players gene regulation. This thesis examines the functional properties of regulatory RNAs in the context of bacterial RNA networks. More specifically, the three studies presented here examine signaling dynamics and crosstalk within the CsrA and Hfq-dependent small RNA regulatory systems; each of these systems (i) contain non-coding RNAs which regulate the translation of multiple target messenger RNAs, (ii) have central roles in coordinating their cells' adaptation to environmental change, and (iii) are evolutionarily conserved across a wide range of bacterial species. In this work, a combination of synthetic biology and mathematical modeling are brought to bear to uncover the operational behavior and potential of the these two model RNA networks.

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