1. Engineering Biological Circuits
Colin Warburton

3. Project Fallot & My Project
My Project
Investigates
Modelling
Techniques at
Protein Level

4. Model Focus: The Phage λ Virus
• Instead of jumping straight into modelling
processes in heart development…
• …Model something that is well known and
understood - aim is to develop a modelling
process which can then be applied to CHD
processes
• Phage is a virus that infects E. Coli, has a low
gene count, known processes, and measured
behaviour

5. The Phage λ Virus

6. Phage λ Virus Strategies
Phage λ has two reproduction
strategies Lysis and Lysogeny.
• Lysis: E. Coli cell is instructed to
use its resources to create many
Phage viruses, this kills the E. Coli
cell. More likely when cell is well
fed, and Phage population is low.
• Lysogeny: Merges with host cells
DNA. E. Coli cell can then revert
to Lysis if damage is detected in
the E. Coli cell. More likely when
Phage population is high.

7. Genetics 101
Degrades
CI
CI
CI
RNA CI
CI
CI
Produces
Binds with
Binds with
Promoter
cI
Operator Site Gene

8. Stochastic Effects
• Normal model chemical reactions with
differential equation i.e:

9. Stochastic Effects
• However if there is:
– Only one reaction site (rectangle)
– The next reaction depends on what protein type
(circle) collides with it first

10. Stochastic Effects
• Next reaction can only be with one protein
type not both!

11. Stochastic Effects
• Next reaction can only be with one protein
type not both!

12. Stochastic Effects
• Reaction is irreversible
• State depends on which protein collides with
the reaction site first

13. Stochastic Effects
• Low concentrations cause random effects
• Reactions can’t be modelled using ODE’s as
need to include probability factors

14. Phage λ Genome

15. Phage λ Reaction Model
Shows all reactions
in Lysis / Lysogeny
decision
Is an example of a
Reaction model,
does not show
behaviour, this is
what the model
that is being
implemented will
predict

16. Reaction Abstraction
ProdCIII CIII DegCIII
ProdCro Crot DegCro
ProdN N
ProdCI
CIt DegCI
DegN PreProdCI
ProdCII CII DegCII

17. Example CI Production Rate

18. Logical Abstraction

19. Logical Abstraction
On
Off
Low
High Concentration
Concentration

20. Similarities to Electronics

21. Validation
• Compare model results with lab
measurements

22. Summary
• Modelling biological process using various
techniques drawn directly from Elec Eng
• Future Work:
– Adapt Phage model, into generic tool set to be
used to model Delta-Notch protein signalling and
dynamics (important in CHD)