Biology Reference
In-Depth Information
TABLE 15.3
Global Tolerances to Change in Parameters (and Independent Variables)
½
T
D
;
T
I
ð
l
;
P
j
Þ
with Assumed Values
for Operating Points in Each of the Regions in System Design Space (see
Figure 15.4
)
Region
Log (Operating Point)
Parameters
Independent Variables
k
S
k
P
S
P
1
(
þ
2,
þ
1)
½
10
;N
½N;
10
½
1000
; N
½N;
1000
2
(
þ
2,
1)
½
10
;
10
½
10
;
10
½
10
;N
½N;
10
*
3
(
2,
þ
1)
½
10
;
10
½
10
;
10
½N;
10
½
10
; N
4
(
2,
1)
½N;
10
½
10
; N
½N;
1000
½
1000
;N
*Notation: [fold decrease, fold increase].
its DNA from the host chromosome and initiates lytic
growth. The key regulatory interactions involved in main-
taining the alternative fates of lambda are shown sche-
matically in
Figure 15.6
.
level of DNA damage that initiates induction
[57]
and the
subsequent progress of lytic development
[58]
.
The core regulator of the lysogenic state is the CI
protein, which as a dimer represses the early lytic tran-
scripts from promoters pL and pR by binding to operator
sites OL and OR while activating its own transcription from
promoter pRM at low concentrations and repressing it at
high concentrations. Following DNA damage, which leads
to an SOS response, RecA protein is activated and stimu-
lates CI monomer auto-cleavage. The lowering of CI
concentration, and hence the dimer concentration, results in
deactivation of cI transcription and de-repression of lytic
functions. A diagram emphasizing the core features of CI
regulation is shown in
Figure 15.7
, along with a version
having symbols that simplify the mathematical notation.
Developmental Decisions
The lytic/lysogenic decision of phage lambda has long been
studied as a model of cell-fate decisions in higher organ-
isms, and has also been explored by mathematical
modeling
[52,53]
. The regulator CII (not shown) initially is
a critical agent in this decision, but once the developmental
path to lysogeny is established it no longer plays a role
[54]
.
The lysogeny/induction decision has received less attention
as a model system, but it has also been well studied. The
classic view held that CRO and CI form a double-negative
bistable switch that plays an essential role in initiation of
the induction process
[55]
. However, there is now evidence
suggesting that CRO is not required for initiation of
induction
[56
Kinetic Model
Early mathematical models of this system have been
reviewed by Santillan and Mackey
[59]
. Well-established
58]
, although it can influence the threshold
e
FIGURE 15.6
Key regulatory circuits maintaining the
alternative fates of bacteriophage lambda. Two regu-
lators maintain the lytic mode of replication; the N-gene
product is a positive regulator required for activating
transcription of the lytic-specific genes and CRO is
a negative regulator required for repressing transcription of
the lysogenic-specific genes. One regulator maintains the
lysogenic mode of replication; the CI gene product is
a negative regulator of the lytic transcripts and a positive
regulator of its own transcription.
