Bacterial Regulatory Circuits are Linked and Extended by Small RNAs.

I was lucky to start my research career as the molecular biology revolution was taking hold, providing a constantly increasing set of tools and questions to investigate. Starting from a fascination with bacteria and their ability to adapt to different conditions, I've investigated post-translational mechanisms and their role in the ability of E. coli to respond to stress. My research career has been primarily at the National Institutes of Health, where I run a group within the Laboratory of Molecular Biology, NCI and hold the title of NIH Distinguished Investigator. Our lab has been interested in both energy-dependent proteolysis, discussed very briefly here, and small regulatory RNAs (sRNAs). The major group of such sRNAs act by pairing with target mRNAs with the aid of the RNA chaperone Hfq, mediating both positive and negative regulation of translation and mRNA stability. Both in our own lab and in a continuing and highly productive collaboration with the laboratory of Gisela (Gigi) Storz, we have used global approaches to identify novel sRNAs, identified how many of them are regulated, both at the level of transcription and stability, and worked on understanding the role of these sRNAs in regulatory networks. Our continued work explores regulators of sRNA and Hfq function. Here, Gigi and I have split summaries of our findings, and hope that our two chapters will be read together.