Quorum Sensing Circuitry - Engineering Biological Signaling for Superior Cell Function William E. Bentley Robert E. Fischell Distinguished Professor & Chair Fischell Department of Bioengineering, Department of Chemical and Biomolecular Engineering, and Institute for Bioscience and Biotechnology Research University of Maryland, College Park

What does bacterial cell-cell signaling do? Myxococcus Paenibacillus vortex enables “talk” S. aureus

Motivation: E. coli (EHEC) P. aeruginosa (cystic fibrosis) Intracellular signaling AI-1 AI-2 intercellular signaling disease S. aureus

Can learn from nature and “tune” biological systems? Did you fix the sink yet?

Alternative motivations – synthetic biology

LuxS lsrG lsrF lsrB lsrC lsrD lsrA lsrR LsrR ATP ADP lsrK LsrK E. coli CRP cAMP ss + - LsrA luxS Glucose or PTS sugars - - LsrC LsrD LsrA pfs - SAH SRH AI-2 P P LsrB Wang et al., J. Bact., 187: , Wang et al., J. Bact., 187: , Gonzalez-Barrios, J. Bact., 188: , 2006 Li et al., J. Bact., 189: , 2007 Mechanisms of quorum machinery in E. coli …

Current Efforts - WEB Biology has extraordinary ability to sense and interpret cues, and take action – at length scales far smaller than man-made machines. Moreover, these cues can vary from small molecules to nearest neighbors and can include physical states. Bacterial “quorum sensing” (QS) provides a rich “tapestry” for understanding biological signal transduction. QS also provides both a conceptual and physical platform for creating a next generation sensor/actuator systems – both within cells and within devices. Our goal is to understand the system, abstract its features, and develop (1) cells that behave in controlled ways in a directed, but autonomous manner and (2) a device that enables two-way (biological ↔ abiological) communication and actuation.

“Plug & Play” Cassette Two demonstrations: 1. autonomous protein production 2. guiding “social” interactions 2. guiding “social” interactions T7pol

Thanks for your attention!! Questions? Thanks to our sponsors: NSF, DTRA, EPA, ONR, & RW Deutsch Foundation