Rebecca Page

Research Interests

How we sense and react to our environment is communicated in the cell by vast networks of highly dynamic, interacting proteins. These interactions are regulated in both space and time, and it is this tight regulation that allows signals from outside of the cell to be rapidly and precisely transmitted to the nucleus leading to the appropriate, and healthy, cellular response. My research integrates structural biology, biophysics and biochemistry in order to understand how these signals in both prokaryotes and eukaryotes are communicated in the cell at atomic resolution. During the last years, my group has focused on two problems: (1) how do toxin:antitoxin (TA) systems in bacteria lead to bacterial persistence and antibiotic resistance and (2) how are the activities of ser/thr phosphatases in the eukaryotic cell regulated. Our studies have made a transformative impacts in both fields. In microbiology and persistence, we: (1) discovered an entirely novel TA system (Type V; published in Nature Chemical Biology) and showed that a second TA system, MqsRA, defines a novel Type II subtype. In the second, a tour de force of crystallographic and functional studies led to the discovery of an entirely novel mechanism of substrate selection in ser/thr phosphatases: namely, that many PSP targeting and inhibitor proteins function to select substrates through a mechanism of steric inhibition. Furthermore, it also revealed the molecular basis by which the blockbuster immunosuppressants FK506 and cyclosporin A work—they bind and block one of the key calcineurin substrate binding grooves, demonstrating, for the first time, how these ubiquitous PSPs can be exploited for the development of highly specific drugs.