synthetic biology: new engineering rules for emerging discipline andrianantoandro e; basu s; karig d...
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![Page 1: Synthetic biology: New engineering rules for emerging discipline Andrianantoandro E; Basu S; Karig D K; Weiss R. Molecular Systems Biology 2006](https://reader034.vdocuments.us/reader034/viewer/2022051401/56649e5d5503460f94b5535a/html5/thumbnails/1.jpg)
Synthetic biology: New engineering rules for emerging discipline
Andrianantoandro E; Basu S; Karig D K; Weiss R.
Molecular Systems Biology 2006
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Overview: Abstract hierarchy for synthetic biology
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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
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Abstract hierarchy for synthetic biology
• Ways to achieve predictability and reliability:
– Utilising large number of independent cells– Synchronising individual cells through
intracellular communication
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Overview: Abstract hierarchy for synthetic biology
Biological devices
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Biological devices
• Biochemical reactions:
– Transcription/translation– Protein phosphorylation– Allosteric regulation – Ligand/receptor binding– Enzymatic reactions
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Biological devices: Non-coding RNA device
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Biological devices: Allosteric protein
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Biological devices:Engineered E. Coli periplasmic receptors
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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
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Overview: Abstract hierarchy for synthetic biology
Biological modules
Biological devices
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Biological modules
• Compartmentalised set of devices with interconnected functions that performs complex tasks
– Transcriptional regulation networks– Signal transduction pathways– Metabolic pathways
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Biological modules: Interfacing devices
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Biological modules: Transcriptional cascade modules
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Biological modules: Coherent feedforward module
Transient Persistent
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Biological modules: Incoherent feedforward module
Input
X
Y
Z
Output
Pulse generator
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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.
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Overview: Abstract hierarchy for synthetic biology
Biological modules
Biological devices
Cellular context
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Cellular context
• Relevant cellular context:
– DNA and RNA metabolism – Availability of amino acids– ATP levels– Protein synthesis– Cell cycle and division– Endogenous signalling pathways
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Cellular context
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Overview: Abstract hierarchy for synthetic biology
Biological modules
Biological devices
Cellular context
Multicellular systems
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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
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Multicellular systems: population control circuit
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Overview: Abstract hierarchy for synthetic biology
Biological modules
Biological devices
Cellular context
Multicellular systems