Susan Gottesman

My work has centered on energy-dependent proteolysis and how protein turnover is used in regulatory circuits. Using the powerful genetics available in Escherichia coli, we first found that the Lon ATP-dependent protease independently regulates capsule synthesis, cell division after DNA damage, and bacteriophage lambda development by rapid degradation of specific regulatory proteins. Biochemical studies led us to the identification of a novel class of two component proteases, ClpAP and ClpXP. The regulatory ATPases of these proteases select distinct substrates for degradation and also act in a chaperone-like fashion in some circumstances. In order to understand how proteolysis of a given protein contributes to the regulatory circuit, we have also investigated the regulation of synthesis of specific unstable proteins. This work has recently led to studies on a small regulatory RNA, DsrA, that acts as a translational regulator of a key transcriptional regulator, RpoS, and also regulates a transcriptional silencer, HNS. DsrA seems to be one of a growing number of novel regulatory RNAs.