Quorum Sensing Circuitry - Engineering Biological Signaling for Superior Cell Function

William E. BentleyRobert 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

Intracellular signaling

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 lsrAlsrR

LsrRATP

ADP

lsrK

LsrK

E. coli

CRPcAMPs

+

-

LsrA

luxS

Glucose or PTS sugars-

-

LsrC

LsrDLsrA

pfs

pfs

-

SAHSRHAI-2

PP LsrB

Wang et al., J. Bact., 187:2066-76, 2005.Wang et al., J. Bact., 187:8350-60, 2005.Gonzalez-Barrios, J. Bact., 188:305-316, 2006Li et al., J. Bact., 189:6011-6020, 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

T7pol

Thanks for your attention!!

Questions?

Thanks to our sponsors: NSF, DTRA, EPA, ONR, & RW Deutsch Foundation