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

2. Overview: Abstract hierarchy for synthetic biology

3. 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

4. Abstract hierarchy for synthetic biology Ways to achieve predictability and reliability: –Utilising large number of independent cells –Synchronising individual cells through intracellular communication

5. Overview: Abstract hierarchy for synthetic biology Biological devices

6. Biochemical reactions: –Transcription/translation –Protein phosphorylation –Allosteric regulation –Ligand/receptor binding –Enzymatic reactions

7. Biological devices: Non-coding RNA device

8. Biological devices: Allosteric protein

9. Biological devices:Engineered E. Coli periplasmic receptors

10. Biological devices: transcription/translation control vs. protein-protein interaction Transcription/translation control Protein-protein interaction Pros  Flexible and easy to build  Useful properties: o Signal amplification o Combinatorial 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

11. Overview: Abstract hierarchy for synthetic biology Biological modules Biological devices

12. Biological modules Compartmentalised set of devices with interconnected functions that performs complex tasks –Transcriptional regulation networks –Signal transduction pathways –Metabolic pathways

13. Biological modules: Interfacing devices

14. Biological modules: Transcriptional cascade modules

15. Biological modules: Coherent feedforward module Transient Persistent

16. Biological modules: Incoherent feedforward module Input X Y Z Output Pulse generator

17. 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.

18. Overview: Abstract hierarchy for synthetic biology Biological modules Biological devices Cellular context

19. Relevant cellular context: –DNA and RNA metabolism –Availability of amino acids –ATP levels –Protein synthesis –Cell cycle and division –Endogenous signalling pathways

20. Cellular context

21. Overview: Abstract hierarchy for synthetic biology Biological modules Biological devices Cellular context Multicellular systems

22. Distribute synthetic networks among multiple cells to form artificial cell-cell communication systems: –Increases number of design possibilities –Overcome limited reliability of individual cells

23. Multicellular systems: population control circuit

24. Overview: Abstract hierarchy for synthetic biology Biological modules Biological devices Cellular context Multicellular systems