RTK

1
?????????? ??
?? ???? 2?? ??????? 3?? ?????????????? 4??
??????????????? 5?? ?????????? 6?? ????
2
????????
1.??? ???????????? 2.??????? 3.???? ???????
???????????????
3
????????
1.??? ???????????? 2.??????? 3.???? ???????
???????????????
4
??????????????????
2. Circuit Engineering Genetic Circuits
1??? ???????????,??????????
????t 0????xA0
x(t)
???? Memoryless property ??????????????????????
t
5
??????????????????
2. Circuit Engineering Genetic Circuits
??1???leaky integrator(?????) 1????????(??????)?
???
Leak (??)
Integrator (???)
t
I
x(t)
I
????t 0????x 0
????????????????????? ?????????????????????????
t
t
6
????????????????
7
?????????????????????????
8
?????????????????????????
9
?????????????????????????
10
?????????????????????????
k0.01(??)
k1
k100(??)
11
?????????????????????????
k0.01(??)
1
k1
k100(??)
0.01
0.63
12
?????????????????????????
k0.01(??)
1
k1
k100(??)
0.01
0.63
- ?????????????? - ???????????????????????????????
????????????????????????????? ????????????????????
??????????
13
????????
1.??? ???????????? 2.??????? 3.???? ???????
???????????????
14
Ca 2????
cameleon
Cameleon Nano (Kd15nM))
Cameleon3.6 (Kd215nM)
Ca??? Kd(nM) kf(1/M/sec) kb(1/sec)
Cameleon3.60 215 1.33106 0.33
Cameleon-Nano15 15 2.36107 0.33
15
?????????(???????)
Cameleon 3.6 Cameleon Nano15
????
Dose response
??????????
??????????
?????
EC5015nM
EC50215nM
16
Ca2??????
Cameleon Nano(Kd15nM))
Cameleon3.6(Kd215nM)
???????ltlt100nM
?? ? ?? ?
??? ? ??? ?

• ???????????Kd??????????

17
????????
1.??? ???????????? 2.??????? 3.???? ???????
???????????????
18
???????????Ca2??????????
Z(Protein)
AZ(complex)
AB(complex)
B(Probe)
????????????????? Ca2????????????
19
Ca2????????- Ca2??????????-
????????????? ???????????? (200µM) ???????????? ???????????????? (20µM) ?????????? ???????????? (2µM)

20
????????
1.???????????? ???????????? 2.??????? 3.????
??????? ???????????????
21
?????????????????
?????????????????
Matlab demo Low-pass
A
AB
t
time
time
If A ltlt Kd
A
AB
time
tims
A
AB
w
wc 1/t
time
time
22
??????????????
?????????????????
Matlab demo Low-pass
A
AB
t
time
time
If A ltlt Kd
A
AB
time
tims
A
AB
w
wc 1/t
time
time
23
??????????????
???????????
??? ????????
pEGFR
time
24
????????EGFR inhibitor????activator?!
pAkt
time
25
?????????????
????
??????
???
???
???
???
???
???
???????????????????????????????? ?
?????????(???) ????
26
???????Akt pathway????????
????
pEGFR
pAkt
pS6
27
???????vs????????????v???????
????
Time
???????? ?????
???????? ?????
???? gt ??? ? ?????Coupling ???? lt ??? ?
???????Decoupling
Matlab demo
????
Time
Time
Coupling
Decoupling
27