Engineering Biological Circuits

Colin Warburton

Project Fallot & My Project

My Project Investigates Modelling Techniques at Protein Level

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

The Phage λ Virus

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.

Genetics 101

cI

RNA

CI

Promoter

GeneOperator Site

Degrades

Binds with

Binds with

CICI

CICI

CI

Produces

Stochastic Effects

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

Stochastic Effects

• However if there is:– Only one reaction site (rectangle)– The next reaction depends on what protein type

(circle) collides with it first

Stochastic Effects

• Next reaction can only be with one protein type not both!

Stochastic Effects

• Next reaction can only be with one protein type not both!

Stochastic Effects

• Reaction is irreversible• State depends on which protein collides with

the reaction site first

Stochastic Effects• Low concentrations cause random effects • Reactions can’t be modelled using ODE’s as

need to include probability factors

Phage λ Genome

Phage λ Reaction ModelShows 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

DegCIProdCI

ProdCro

PreProdCI

DegCIII

DegCIIProdCII

ProdCIII

DegN

ProdN N

CII

CIII

CIt

DegCroCrot

Reaction Abstraction

Example CI Production Rate

Logical Abstraction

Logical AbstractionOn

OffLow ConcentrationHigh

Concentration

Similarities to Electronics

Validation

• Compare model results with lab measurements

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)