Title: RTK
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oad? http//kurodalab.bi.s.u-tokyo.ac.jp/iwanami/
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32. Circuit Engineering Genetic Circuits
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1.????????? (????????1???)
I
DEMO Lowpass
42. 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?????????????????
Action potential (????)
???
Time
????
Recd. elec
Stim. elec
Time
cm3
7Positive and negative feedback loops
Positive and negative feedback loop??????
(1) Hodgkin and Huxley model Spike/FiringAction
potential
Recd. elec
Stim. elec
7
8Positive and negative feedback loopsImpulse??????
??????
Positive and negative feedback loop??????
(1) Hodgkin and Huxley model Spike/FiringAction
potential
?????????? ????????????? ??????????
8
9Positive 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
10Positive 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
11Positive and negative feedback loops
Hodgkin and Huxley model
??????(Voltage clumped)
K channel
Na channel
12Positive and negative feedback loops
Hodgkin and Huxley model
??????(Voltage clumped)
K channel
Na channel
13Positive and negative feedback loops
Hodgkin and Huxley model
??????(Voltage clumped)
K channel
??????????????????? ????(????) ?????Akt?Rap1???
14Positive and negative feedback loops
?????????????????????? m???????h??????? Ras??????
????3??????????????????????
Hodgkin and Huxley model
Na channel
15Positive and negative feedback loops
Hodgkin and Huxley model
??????(Voltage clumped)
K channel
Na channel
16Positive and negative feedback loops
Hodgkin and Huxley model
Na channel
K channel
17Positive and negative feedback loops
Hodgkin and Huxley model
Na channel
K channel
18Positive and negative feedback loops
Hodgkin and Huxley model
Na channel
K channel
19Positive and negative feedback loops
Hodgkin and Huxley model
20Positive feedback loops
Positive Feedback Loop?Bistability???
DEMO feedback.g
20
21Positive feedback loops
Positive Feedback Loop?Bistability???
Sub2-P?????????time course???
21
22Positive 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
24Leaky integrate-and-fire model
H H model????????????? ??????? ????(fire)
24
25Distinct properties of oscillators
Negative feedback ??????amplitude????
Positive and negative feedback?????????(??)????
Nature Cell Biology (2003) 5, 346-351.
Pomerening JR, Sontag ED, Ferrell JE Jr.
26Possible 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.
27Distinct properties of oscillators
Negative feedback ??????amplitude????
Negative???positive and negative
feedback???oscillator???????? ?????(Ksynth)???????
???????????!
Tsai,, T. Y. et al, Science, 321, 126, 2008
28Distinct properties of oscillators
??????????????????? ???(frequency)???(Amplitude)??
???
Negative feedback ??????amplitude????
Positive and negative feedback
??????frequency????
29(No Transcript)
30??????
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31????????????????
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?????? vs ??????
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33?????? vs ??????
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34???????????????????
Cell
Biased
Genome
Transcriptome
Proteome
Metabolome
35Insulin 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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37(No Transcript)
38?????????????????????????
Insulin
?
phosphoproteome
- ???
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- ???????????????
?
metabolome
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Insulin
phosphoproteome
- ???
metabolome
40?????????????????????????
Insulin
phosphoproteome
- ???
- ????
metabolome
41?????????????????????????
Insulin
phosphoproteome
- ???
- ????
- ?????????
metabolome
42?????????????????????????
Insulin
phosphoproteome
- ???
- ????
- ?????????
- ??????????????????
metabolome
43?????????????????????????
Insulin
phosphoproteome
- ???
- ????
- ?????????
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- ???????????????
metabolome
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Phospho-proteome
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