Transcript Synthetic biology: New engineering rules for emerging discipline

Synthetic biology: New engineering
rules for emerging discipline
Andrianantoandro E; Basu S; Karig D
K; Weiss R.
Molecular Systems Biology 2006
Overview: Abstract hierarchy for
synthetic biology
Abstract hierarchy for synthetic biology
• A major problem with using the engineering
approach to construct biological systems is the
lack of predictive power that stems from several
sources of uncertainty.
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Gene expression noise
Mutation
Cell death
Changing extracellular environment
Interactions with cellular context
Abstract hierarchy for synthetic biology
• Ways to achieve predictability and
reliability:
– Utilising large number of independent cells
– Synchronising individual cells through
intracellular communication
Overview: Abstract hierarchy for
synthetic biology
Biological devices
Biological devices
• Biochemical reactions:
– Transcription/translation
– Protein phosphorylation
– Allosteric regulation
– Ligand/receptor binding
– Enzymatic reactions
Biological devices: Non-coding
RNA device
Biological devices: Allosteric
protein
Biological devices:Engineered E.
Coli periplasmic receptors
Biological devices:
transcription/translation control vs.
protein-protein interaction
Transcription/translation
control
Pros
Cons
 Flexible and easy to build
 Useful properties:
oSignal amplification
oCombinatorial control
Protein-protein interaction
 Changes in output are very fast
 Possible to amplify signals
 Use modest amount of cellular
resources
 Easy to insulate devices from
endogenous cellular processes
 Changes in output are slow  Proteins must be well characterised
 Large amount of cellular
resources consumed
Overview: Abstract hierarchy for
synthetic biology
Biological modules
Biological devices
Biological modules
• Compartmentalised set of devices with
interconnected functions that performs
complex tasks
– Transcriptional regulation networks
– Signal transduction pathways
– Metabolic pathways
Biological modules: Interfacing devices
Biological modules: Transcriptional
cascade modules
Biological modules: Coherent
feedforward module
Transient
Persistent
Biological modules: Incoherent
feedforward module
Input
X
Y
Z
Output
Pulse generator
Biological Modules: Summary
• Biological devices have to redesigned.
• Cascade modules can achieve
ultrasensitivity.
• Coherent feedforward modules can
construct persistence detectors.
• Incoherent feedforward modules can
construct pulse generators.
Overview: Abstract hierarchy for
synthetic biology
Cellular context
Biological modules
Biological devices
Cellular context
• Relevant cellular context:
– DNA and RNA metabolism
– Availability of amino acids
– ATP levels
– Protein synthesis
– Cell cycle and division
– Endogenous signalling pathways
Cellular context
Overview: Abstract hierarchy for
synthetic biology
Multicellular
systems
Cellular context
Biological modules
Biological devices
Multicellular systems
• Distribute synthetic networks among
multiple cells to form artificial cell-cell
communication systems:
– Increases number of design possibilities
– Overcome limited reliability of individual cells
Multicellular systems: population
control circuit
Overview: Abstract hierarchy for
synthetic biology
Multicellular
systems
Cellular context
Biological modules
Biological devices