How Do Cells Compute? John J. Tyson Department of Biological Sciences Virginia Bioinformatics...
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Transcript of How Do Cells Compute? John J. Tyson Department of Biological Sciences Virginia Bioinformatics...
How Do Cells Compute?
John J. TysonDepartment of Biological Sciences
Virginia Bioinformatics Institute
Do Cells Compute?
Computer
bit string bit string
N N2
x x
01
00
10
11
1
0
1
0
either A or Bbut not both
computations
decisions
Is the cell anInformation Processing System?
IPSinput output
Cellnutrients
repellants
damage
hormones
heat shock
growth & division
movement
geneexpression
death
BacteriaGlucose
Lactose
1
0
glucosemetabolizing
enzymes
1
lactosemetabolizing
enzymes
0
BacteriaGlucose
Lactose
lactosemetabolizing
enzymes
1
1 0
glucosemetabolizing
enzymes
1
BacteriaGlucose
Lactose
lactosemetabolizing
enzymes
0
1 1
glucosemetabolizing
enzymes
1
BacteriaGlucose
Lactose
lactosemetabolizing
enzymes
0
0 0
glucosemetabolizing
enzymes
1
Fission Yeast
14 m
7 m
Wild type Mutant (wee1)
“size control” different “set point”
Fibroblast
Ionizing radiationdamages DNA
cell cycle arrest
repair
Fibroblast
ProgrammedCell Death
Is a cell like a computer?
Laptop Cell
Solid state Watery
Programmable Hard-wired
Precise Sloppy
Digital Analog
Sequential Parallel
Manufactured Self-reproducing
Designed Evolved
Silicon CarbonSilicon Carbon
DGaD LoDD
…in the last 5 years
“Molecular Systems Biology”
CellCarbon
Watery
Hard-wired
Sloppy
Analog
Parallel
Self-reproducing
Evolved
Carbon
20 years ago…
Winfree & Kauffman
Oster & Perelson
Goldbeter & Segel
Glass & Mackey
Rinzel & Keizer
Goodwin, Meinhardt, Odell, Tyson, …
CellCarbon
Watery
Hard-wired
Sloppy
Analog
Parallel
Self-reproducing
Evolved
Carbon
How do cells make decisions?
WT
cdc
wee
Paul Nurse, Nature (1975)
Fission Yeast
P Wee1
Wee1P
Cdc25
CycB
CycB
Cdc25
MPFMitosis Promoting Factor
++P
WT
cdc
wee
cdc25ts
wee1ts
wee1OP
cdc25OP
Fission Yeast
P Wee1
Wee1P
Cdc25
CycB
CycB
Cdc25
mass/ DNA
0 1 2
Cdc2/Cdc13
10-3
10-2
10-1
100
S/G2
M
size
MP
F
size
SN14m
wee1OPwee1
P++
DNA synthesis
Mitosis & Cell Division
0.01 0.1 1 10 100 1000 10000
1
10
100
1000
0.4
3.0
WT
Cdc25 activity (%)
Wee
1 ac
tivity
(%
) cdc
cut
wee
quantized
Size at Division1.0 = WT size
wee1ts
wee1OP
cdc25OP
cdc25ts
P
Cdc25
Wee1
Wee1P
Cdc25
CycB
PCdc20
Cdc20
APC-PAPC
CycB
0
0.5
1
0 1 2
MP
F
total cyclin
ks
MPF
Joe Pomerening
Cell (2005)
MPF
total cyclin
How do cells compute?
Switches and Clocks
ks
MPF
mass/ DNA
0 1 2
Cdc2/Cdc13
10-3
10-2
10-1
100
S/G2
M
size
MP
F
The class of chemical switching networks will be promising
candidates for a possible new technology of chemical reaction
systems.
nutrients
repellants
damage
hormones
heat shock
growth & division
movement
geneexpression
death
The living cell is Rössler’s“flüssiges Automata”:
a miniature, self-reproducing, water-soluble biochemical
computer.
$$: DARPA, NIH, McDonnell Foundation