engineering biological circuits, warburton, colin
DESCRIPTION
TRANSCRIPT
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)