Synthetic biology: New engineering rules for emerging discipline Andrianantoandro E; Basu S; Karig D K; Weiss R. Molecular Systems Biology 2006.

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