Summary Lecture 3 Image by MIT OCW.

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Summary Lecture 3

Image by MIT OCW.

L4: Cooperativity & introduction

λ phage model

λ phage model (Hasty et al.) as example for applying mass action law.

K

2

λ λ

λ λ

OR2 OR3

λ λ

OR2 OR3

λ λ λ λ

OR2 OR3 biology

K

1

λ

λ

2X ←

K

1

X

2 most important step in modeling !!

D + X

2

K

2

D + X

2

K

3

DX

2

DX

*

2 most important

DX

2

+

DX

2

X

+

⎯ k d

P

X

2

K

4

DX

2

DX

2

⎯ k t

DX

2

+ P + nX

A step in modeling !!

math fast slow

2X ←

K

1

D + X

2

K

2

X

2

DX

2

D + X

2

K

3

DX

*

2

DX

2

+

DX

2

X

+

⎯ k d

P

X

2

K

4

DX

2

DX

2

⎯ k t

DX

2

+ P + nX

A mass action dx dt

σ

σ

1

2

=

=

=

1 + (1 + σ

1

)x

2

K

3

K

2

K

4

K

2

α x

2

+ σ

2 x

4 constants

− γ x + 1 relative binding

α

γ

=

= nk t p r

0 d

T r k d

K

1

K

2

~ synthesis/basal rate

~ degradation/basal rate choose elegant (dimensionless, relative) variables !

graphical stability analysis

How to experimentally verify these ideas ?

Synthetic Biology

Build your own designed network ‘from scratch’ and test your model

Examples for synthetic genetic switches:

Isaacs et al.

Prediction and measurement of an autoregulatory genetic module. PNAS 100 , 7714 (2003)

Gardner et al.

Construction of a genetic toggle switch in Escherichia coli. Nature 403 , 399 (2000)

First a short intro on ‘Genetic Engineering’

Toolbox of the genetic engineer:

1. Restriction enzymes

2. Plasmids

3. PCR (Polymerase Chain Reaction)

4. Fluorescent proteins

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