This event will be held virtually via Zoom – check email for details or contact ksas@seas.upenn.edu

Protein modules that are responsive to small molecule inputs have enabled control of cellular processes for decades’ worth of important mechanistic studies. More recently, they have gained attention as a means of control for improved safety of cellular therapies. To date, most small molecule-responsive systems have been adapted from natural proteins, which provide limited control behaviors and often rely on small molecules with non-ideal properties for use in humans. I will describe how we have used computational protein design to move beyond these naturally occurring systems to create a new set of molecular tools that are responsive to multiple clinically approved drugs. The unique architecture of our system enables more complex control behaviors for multiple cellular outputs. I will describe applications of this designed system in the control of mammalian cytoskeletal signaling, transcription, and CAR T-cell therapy.