Information Processing Networks in Living Cells

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Information Processing Networks in Living Cells

• John J. Tyson
• Biological Sciences
• Virginia Tech

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Collaborators
Funding Agencies
Kathy Chen Jill Sible Bela Novak Attila Csikasz
DARPA McDonnell Found
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Cell signaling
Hanahan Weinberg (2000)
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Information Processing Systems
Laptop
Cell
Silicon
Carbon
Silicon
Carbon
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Signal Transduction Network
Hanahan Weinberg (2000)
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Gene Expression
S
R
Signal-Response Curve
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Protein Phosphorylation
Kinase
ADP
ATP
R
RP
H2O
Pi
Phosphatase
Goldbeter Koshland, 1981
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Protein Synthesis Positive Feedback
S
Open
R
EP
E
Closed
Bistability
Fuse
Griffith, 1968
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dying
Example Fuse
response (R)
living
signal (S)
Eissing et al. (2004) J Biol Chem 27936892
Apoptosis (Programmed Cell Death)
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Coupled Buzzers
1
S Rtotal
S0.5
S1.5
S1
E
R
RP
0.5
E
EP
0
0
0.5
1
1.5
R
Bistability
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Frog egg
Wee1
MPF
MPF-P
MPF
CycB
(inactive)
M-phase Promoting Factor
Cdc25-P
Cdc25
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MPF activity depends on total cyclin
concentration and on the history of the extract
M
I
Cyclin concentration increasing
M
MPF activity
I
I
I
I
I
I
nM Dcyclin B
Cyclin concentration decreasing
inactivation threshold at 90 min
MPF activity
bistability
Wei Sha Jill Sible (2003)
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Oscillations
MPF
cyclin
cyclin synthesis
cyclin degradation
APC
MPF
MPF-P
(inactive)
Cdc25-P
Cdc25
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Pomerening, Kim Ferrell Cell (2005)
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Wee1
P
Cdc20
Cdc14
TFBA
Wee1
TFBI
CycB
P
APC-P
APC
Cdc14
Cdc25
P
Cdc20
CycB
Cdc14
Cdc25
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Wee1
P
Cdc20
Cdc14
TFBA
Wee1
TFBI
CycB
P
APC-P
APC
Cdc14
Cdc25
P
Cdc20
CycB
Cdc14
Cdh1
Cdc25
CycD
CKI
CycB
CycE
TFII
Cdh1
CycD
CycA
TFIA
CKI
CKI
CycA
Cdc20
CycA
TFEA
CycB
TFEI
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Cell Cycle Regulation
high MPF
high SPF
DNA replication
primed MEN
fired RC
Cdk2
Cdk1
cell division
CycA
CycB
primed RC
fired MEN
low MPF
low SPF
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SPF
Licensing Factor
Replication Complex
Csikasz-Nagy Novak, 2005
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Primer
MPF
Mitotic Exit Network
Csikasz-Nagy Novak, 2005
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Growth
SPF
MPF
Mitosis
MEN
Cdk2
Cdk1
RC
DNA synthesis
CycA
CycB
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(No Transcript)
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Tyson, Chen Novak, Sniffers, buzzers, toggles
and blinkers, Curr. Opin. Cell Biol. 15221
(2003).