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oad? http//kurodalab.bi.s.u-tokyo.ac.jp/iwanami/
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2. Circuit Engineering Genetic Circuits
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1.????????? (????????1???)
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DEMO Lowpass
4
2. Circuit Engineering Genetic Circuits
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2.??????? (??????????2???)
y
I
I
x
DEMO bandpass
5
??????????????
Repressilator
TetR
Time
??
Repressilator
Time
Michael B. Elowitz Stanislas Leibler
,2000,Nature
6
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Action potential (????)
???
Time
????
Recd. elec
Stim. elec
Time
cm3
7
Positive and negative feedback loops
Positive and negative feedback loop??????
(1) Hodgkin and Huxley model Spike/FiringAction
potential
Recd. elec
Stim. elec
7
8
Positive and negative feedback loopsImpulse??????
??????
Positive and negative feedback loop??????
(1) Hodgkin and Huxley model Spike/FiringAction
potential
?????????? ????????????? ??????????
8
9
Positive and negative feedback loops
Hodgkin and Huxley model

• m, h, n channel opening probability
• m controls Na channel opening
• h controls Na channel closing
• n controls K channel opening

DEMO cm.m
action potential??? positive feedback?? negative
feedback??
9
10
Positive and negative feedback loops
Positive and negative feedback loop??????
(1) Hodgkin and Huxley model Spike/FiringAction
potential
v
m
h
n
n
I
v
t (ms)
10
11
Positive and negative feedback loops
Hodgkin and Huxley model
??????(Voltage clumped)
K channel
Na channel
12
Positive and negative feedback loops
Hodgkin and Huxley model
??????(Voltage clumped)
K channel
Na channel
13
Positive and negative feedback loops
Hodgkin and Huxley model
??????(Voltage clumped)
K channel
??????????????????? ????(????) ?????Akt?Rap1???
14
Positive and negative feedback loops
?????????????????????? m???????h??????? Ras??????
????3??????????????????????
Hodgkin and Huxley model
Na channel
15
Positive and negative feedback loops
Hodgkin and Huxley model
??????(Voltage clumped)
K channel
Na channel
16
Positive and negative feedback loops
Hodgkin and Huxley model
Na channel
K channel
17
Positive and negative feedback loops
Hodgkin and Huxley model
Na channel
K channel
18
Positive and negative feedback loops
Hodgkin and Huxley model
Na channel
K channel
19
Positive and negative feedback loops
Hodgkin and Huxley model
20
Positive feedback loops
Positive Feedback Loop?Bistability???
DEMO feedback.g
20
21
Positive feedback loops
Positive Feedback Loop?Bistability???
Sub2-P?????????time course???
21
22
Positive and negative feedback loops
Positive and negative feedback loop??????
(1) Hodgkin and Huxley model Spike/FiringAction
potential
v
m
h
n
n
I
v
t (ms)
22
23
?????????????????
Action potential (????)
???
Time
????
Recd. elec
Stim. elec
Time
cm3
24
Leaky integrate-and-fire model
H H model????????????? ??????? ????(fire)
24
25
Distinct properties of oscillators
Negative feedback ??????amplitude????
Positive and negative feedback?????????(??)????
Nature Cell Biology (2003) 5, 346-351.
Pomerening JR, Sontag ED, Ferrell JE Jr.
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Possible Cell Cycle Oscillators
Negative feedback
Negative feedback
Positive and negative feedback
Nature Cell Biology (2003) 5, 346-351.
Pomerening JR, Sontag ED, Ferrell JE Jr.
27
Distinct properties of oscillators
Negative feedback ??????amplitude????
Negative???positive and negative
feedback???oscillator???????? ?????(Ksynth)???????
???????????!
Tsai,, T. Y. et al, Science, 321, 126, 2008
28
Distinct properties of oscillators
??????????????????? ???(frequency)???(Amplitude)??
???
Negative feedback ??????amplitude????
Positive and negative feedback
??????frequency????
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(No Transcript)
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????????????????
Hiroyuki Kubota _at_U. Tokyo
Shinya Kuroda _at_U. Tokyo
Katsuyuki Yugi _at_U. Tokyo
Keiichi Nakayama
Tomoyoshi Soga _at_Keio U.
Masaki Matsumoto
32
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?????1821
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33
?????? vs ??????
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???????????????????
Cell
Biased
Genome
Transcriptome
Proteome
Metabolome
35
Insulin signaling-dependent metabolic control
Saltiel, A.R.et al. Nature, 2001
Enzymes
Metabolites
Glucose metabolism
Phosphorylation, allosteric regulation
36
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Phospho-proteome
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(No Transcript)
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?????????????????????????
Insulin
?
phosphoproteome

1. ???
2. ????
3. ?????????
4. ??????????????????
5. ???????????????

?
metabolome
39
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Insulin
phosphoproteome

1. ???

metabolome
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Insulin
phosphoproteome

1. ???
2. ????

metabolome
41
?????????????????????????
Insulin
phosphoproteome

1. ???
2. ????
3. ?????????

metabolome
42
?????????????????????????
Insulin
phosphoproteome

1. ???
2. ????
3. ?????????
4. ??????????????????

metabolome
43
?????????????????????????
Insulin
phosphoproteome

1. ???
2. ????
3. ?????????
4. ??????????????????
5. ???????????????

metabolome
44
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Phospho-proteome
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