Se s o ules wi h inpu ec o sModules
Quo um sensing is a cell densi y dependen gene egula ion
sys em whe eby popula ions o bac e ia communica e h ough small
di usible signalling molecules in o de o coo dina e he exp ession
o speci ic genes such as i ulence ac o s depending on he hei
numbe s, exhibi ing popula ion-le el beha iou .1
In obio icsIn obio ics
F ancisco J. Rome o-Campe o1, Jona han Blakes1, Miguel Cáma a2, Na alio K asnogo 1
1ASAP Resea ch G oup, School o Compu e Science and IT, Uni e si y o No ingham, Jubilee Campus, No ingham, NG8 1BB, UK. { xc, j b,nxk}@cs.no .ac.uk
2The Pseudomonas Quo um Sensing G oup, Ins i u e o In ec ion, Immuni y and In lamma ion & School o Molecula Medical Sciences, Cen e o Biomolecula Sciences, Uni e si y o No ingham. miguel.cama a@no ingham.ac.uk
A sys ems analysis o he AHL Quo um Sensing sys em in
Pseudomonas ae uginosa
Funded by EPSRC & BBSRC g an s
EP/E017215/1& BB/F01855X/1
a → b
[ ]label
a2b3c
Mul ise s o objec sPopula ion o molecules
Memb anesCompa men s
Rew i ing ules on objec s
Molecula in e ac ions
P sys em speci ica ion
Biological en i y
c
high cell densi ylow cell densi y
di ision &
quo a ion
ais ans o med in o bwi h a e c
Name({molecules,...}{cons an s,...}{labels})
Quo um sensing elies on he syn hesis, accumula ion and
subsequen sensing o hese signals, pa icula ly N-acylhomose ine
lac ones (AHLs) in P. ae uginosa:
Composing a quo um sensing module
In ou me hodology a module is a se o ules ha de ine a in eg a ed
biological unc ion, such as un egula ed gene exp ession consis ing
o p oduc ion and deg ada ion o he LasR p o ein om gene lasR:
Modules can be assembled in o la ge modules. He e a LasI UnReg
module, enzyma ic 3OC12 syn hesis and di usion, complexa ion and
posi i e gene egula ion modules a e composed in o he quo um
sensing module QS({LasR,...,RsaL·lasI},{c1,...,c24},{b}) =
signalling molecule
bac e ia
In mos QS sys ems he signals, S, a e syn hesised by an Ienzyme
encoded by a geneI. A ecep o p o ein Rencoded by a geneR
in e ac s wi h S o o m an ac i e ansc ip ion ac o R·Swhich binds
o geneI ampli ying he p oduc ion o Ip o ein and he e o e syn hesis
o S. This ansc ip ion ac o also egula es many o he genes.
N
H
O
O
N-bu y yl homose ine lac one (C4)
N
H
OO
O
N-3-oxo-dodecanoyl homose ine lac one (3OC12)
O
O
• Vi ulence
• Seconda y Me aboli es
• Mo ili y and Swa ming
• Conjuga ion
• Bio ilm De elopmen
•
G ow h Inhibi ion
i
+
R
S
In P. ae uginosa LasR s imula es LasI, and RsaL which sup esses
LasI. This ensu es he apid bu con olled p oduc ion o AHL-
syn hesis equi ed o coo dina e a popula ion pheno ype.
Re e ences
1. Be na dini F, Gheo ghe M, K asnogo N. Quo um sensing P sys ems. Theo . Compu . Sci. 371(1-2): 20-33 (2007)
2. Rome o Campe o FJ. & Pé ez Jiménez MJ. Modelling gene exp ession con ol using P sys ems: The Lac Ope on, a case s udy
3. Alon U. Ne wo k mo i s: heo y and expe imen al app oaches. Na u e Re iews Gene ics 8 (2007) BioSys ems 91 (2008)
When coupled o a nega i e gene egula ion module h ough lasI
a 3OC12 con olled ype 1 incohe en eed- o wa d loop3eme ges.
Modelling quo um sensing he e o e equi es a colony-le el iew wi h
many indi idual copies o he same quo um sensing gene ne wo k in
di e en s a es. O dina y di e en ial equa ions a e p oblema ic o
modelling gene ne wo ks, as low numbe s o molecules dec ease he
signal o noise a io due o he ini e numbe e ec (η~ 1/√N).
P sys ems ep esen a no el disc e e, s ochas ic and mesoscopic
amewo k o modelling cellula sys ems2 ha acili a es he assembly
o ansc ip ional modules, mass duplica ion o cells and ealis ic
kine ics using he well-s udied Gillespie algo i hm, o he obse a ion o
eme gen beha iou s h ough simula ion.
A P sys em consis s o a nes ed memb ane s uc u e (colonies, cells o
in acellula compa men s), con aining mul ise s o objec s (genes,
complexes, me aboli es) which a e ew i en by ules ( eac ions).
LasR
RsaL
LasI
+
−
+speed up by
LasR·3OC12
homeos asis
by RsaL
ype 1 IFFL
•
G ow h Inhibi ion
IR
R
S+
s’
S