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.
– 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
controlProtein-protein interaction
Pros Flexible and easy to build Useful properties:
oSignal amplificationoCombinatorial control
Changes in output are very fast Possible to amplify signals Use modest amount of cellular resources Easy to insulate devices from endogenous cellular processes
Cons Changes in output are slow Large amount of cellular resources consumed
Proteins must be well characterised
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
Biological modules
Biological devices
Cellular context
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
Biological modules
Biological devices
Cellular context
Multicellular systems
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
Biological modules
Biological devices
Cellular context
Multicellular systems