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Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Page 1: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

Simulating A Gene Regulatory Network (GRN)

A Delay Flip-Flop Implementation

Page 2: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

2

Outline Simulation Hill Equation Michaelis-Menten BioD Results

Page 3: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

3

Outline Simulation Hill Equation Michaelis-Menten BioD Results

Page 4: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Simulation

Why do we simulate ?

Page 5: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Simulation Cost effective Fast Proven method

An “analytic” model is appropriate when mathematics can be used to find the exact (deterministic) or probable (stochastic) values of the measures of performance.

We cannot test

Page 6: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Outline Simulation Hill Equation Michaelis-Menten BioD Results

Page 7: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Outline Simulation Hill Equation Michaelis-Menten BioD Results

Page 8: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Hill Equation

Page 9: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Hill Equation

ndegradatio

R from inhibition

tion transcripmax.

][][

1

1.

][mX

KRdt

mXdmXn

R

Q R

Page 10: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Hill Equation

ndegradatio

R from inhibition

leakagetion transcripmax.

][][

1

1.1.

][mX

KR

aadt

mXdmXn

R

Q R

Page 11: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Hill Equation

ndegradatio

R2 from inhibition

2

R1 from inhibition

1

leakagetion transcripmax.

][]2[

1

1.

]1[1

1.1.

][21

mX

KR

KR

aadt

mXdmXn

R

n

R

Q RR

Page 12: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Hill Equation

ndegradatio

A from activationR from inhibition

leakagetion transcripmax.

][][

1

][

.][

1

1.1.

][mX

KA

KA

KR

aadt

mXdmXn

A

n

An

R

Q A

A

R

Page 13: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Outline Simulation Hill Equation Michaelis-Menten BioD Results

Page 14: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Outline Simulation Hill Equation Michaelis-Menten BioD Results

Page 15: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Michaelis-Menten

http://en.wikipedia.org/wiki/Enzyme_kinetics

Page 16: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Outline Simulation Hill Equation Michaelis-Menten BioD Results

Page 17: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Outline Simulation Hill Equation Michaelis-Menten BioD Results

Page 18: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

Page 19: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

][]4[

1

][4

4

1 mCIcr

KGaldt

mCIcrdmCIcrn

Gal

Gal

Page 20: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

][][

1

][

.][

1

1.

][1

][mCI

KOmpR

KOmpR

KOmpRP

KCIIdt

mCIdmCIn

OmpR

n

OmpR

n

OmpRP

n

CII

ompf

OmpR

OmpR

OmpRPCII

Page 21: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

OmpR

OmpR

OmpRPCI n

OmpR

n

OmpR

n

OmpRP

n

CI

ompf

KOmpR

KOmpR

KOmpRP

KCIdt

mCIId

][1

][

.][

1

1.

][1

][

Page 22: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

][][

1

][ 2 mCII

KCIdt

mCIIdmCIIn

CI

CI

Page 23: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

][][

3 mOmpRdt

mOmpRdmOmpR

Page 24: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

]4[][

1

][

.][

1

1.

][1

]4[4 mGal

KOmpR

KOmpR

KOmpRP

KCIdt

mGaldmGaln

OmpR

n

OmpR

n

OmpRP

n

CI

ompf

OmpR

OmpR

OmpRPCI

Page 25: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

OmpR

OmpR

OmpRPCI n

OmpR

n

OmpR

n

OmpRP

n

CI

ompf

KOmpR

KOmpR

KOmpRP

KCIdt

mTetRd

][1

][

.][

1

1.

][1

][

Page 26: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

][][

1

][ 6 mTetR

KLacIdt

mTetRdmTetRn

LacI

LacI

Page 27: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

OmpR

OmpR

OmpRPCII n

OmpR

n

OmpR

n

OmpRP

n

CII

ompf

KOmpR

KOmpR

KOmpRP

KCIIdt

mLacId

][1

][

.][

1

1.

][1

][

Page 28: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

][][

1

][ 7 mLacI

KTetRdt

mLacIdmLacIn

TetR

TetR

Page 29: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

].[].[][

CIImCIIdt

CIIdCIICII

Page 30: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

].[].[][

CImCIdt

CIdCICI

Page 31: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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].[].[]].[12[

.][

12

CImCIK

mCIcrtaR

dt

CIdCICI

taRCI

BioD

Page 32: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Law of Mass Action

Page 33: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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].[].[]].[12[

.][

12

CImCIK

mCIcrtaR

dt

CIdCICI

taRCI

BioD

Page 34: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

].[].[][

OmpRmOmpRdt

OmpRdOmpROmpR

Page 35: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

][

]).[1.(].[

][

OmpRk

OmpRLVOmpRPV

dt

OmpRd

phos

phosdePhos

Page 36: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

].[].[][

]).[1.(][OmpRPOmpRPV

OmpRk

OmpRLV

dt

OmpRPdOmpRPdePhos

phos

phos

Page 37: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

]4.[]4.[]4[

44 GalmGaldt

GaldGalGal

Page 38: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

].[].[][

TetRmTetRdt

TetRdTetRTetR

Page 39: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

].[].[][

LacImLacIdt

LacIdLacILacI

Page 40: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Outline Simulation Hill Equation Michaelis-Menten BioD Results

Page 41: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Outline Simulation Hill Equation Michaelis-Menten BioD Results

Page 42: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Results

Page 43: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

Page 44: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Results

Page 45: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Results

Page 46: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Results

Page 47: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Results

Page 48: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Results

Page 49: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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BioD

Page 50: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Results

Page 51: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Results

Page 52: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Results

Page 53: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Results

Page 54: Simulating A Gene Regulatory Network (GRN) A Delay Flip-Flop Implementation

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Questions…