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?
enables “talk”
Paenibacillus vortex
S. aureus
Myxococcus
Motivation:
Intracellular signaling
AI-2
E. coli
(EHEC)
S. aureus
intercellular signaling
disease
P. aeruginosa
(cystic fibrosis)
AI-1
Intracellular signaling
Intracellular signaling
Can learn from nature and “tune” biological
systems?
Did you fix
the sink yet?
Alternative motivations – synthetic biology
Mechanisms of quorum machinery in E. coli …
LsrR
ATP
LsrA
P
P
lsrK
lsrR
lsrA
-
lsrC
lsrD
ADP
lsrB
LsrB
LsrA
LsrD
lsrF lsrG
+
-
CRP
s
-
cAMP
Glucose or
PTS sugars
pfs
luxS
pfs
LuxS
AI-2
LsrC
SRH
E. coli
SAH
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, 2006
Li et al., J. Bact., 189:6011-6020, 2007
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.
Two demonstrations:
1. autonomous protein production
2. guiding “social” interactions
“Plug & Play” Cassette
T7pol
Thanks for your attention!!
Questions?
Thanks to our sponsors: NSF, DTRA, EPA, ONR,
& RW Deutsch Foundation