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Programmed cells: Interfacing natural and engineered gene networks

This article explores the concept of programmed cells and how natural and engineered gene networks can be interfaced to perform specific functions. It provides examples of biological background, building blocks, and applications such as DNA damage detection and population density control.

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Programmed cells: Interfacing natural and engineered gene networks

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  1. Programmed cells: Interfacing natural andengineered gene networks Kobayashi, Kærn, Araki, Chung, Gardner, Cantor & Collins,( PNAS 2004). You, Cox, Weiss & Arnold ( 2004 NATURE) Noam Vardi

  2. outline • Biological background • The building blocks of a programmed cell • Examples • summary

  3. The central dogma

  4. Repressor A Activator A RNA pol B A RNA pol A B Transcription factors control gene expression • Activators: • Repressors RNA pol ON Gene B OFF Gene B

  5. Cells need to compute in order to survive

  6. Sugar metabolism genes in E.coli • The lac genes are transcribed if and only if: • Absence of glucose • The relevant sugar is present Expression of alternative sugar genes AND gate

  7. A modular programmed cell Kobayashi, Kærn, Araki, Chung, Gardner, Cantor & Collins,( PNAS 2004). engineered regulatory network Sensory module output input • requirments • the regulatory network can read the input • The cell can read the output

  8. Example 1 : interfacing the S.O.S pathway with a genetic switch UV radiation DNA damage RecA SOS repressor SOS genes The SOS pathway in E.coli

  9. A genetic toggle switch Each promoter is inhibited by the repressor transcribed from the opposite promoter B promoter A B PromoterA All or none reaction – when one promoter is ON , the second one is OFF Bi-stable system Phage lambda’s

  10. Phage λ uses a toggle switch to transfer between 2 cycles

  11. Phage lambda toggle switch uses the E.coli SOS system UV radiation DNA damage SOS repressor RecA Lytic phase Lysogenic phase Phage genes ON Phage genes OFF

  12. Interfacing the genetic switch with SOS pathway and an output module GFP output module - GFP UV DNA damage SS DNA Sensory module- SOS system RECA regulatory module- genetic switch ON

  13. The system is applied using plasmids Plasmid - an extra-chromosomal DNA molecule which is capable of replicating E.Coli cell DNA output module GFP Regulatory module

  14. Example 1 - results Treating cells with UV The genetic switch keep the system active long time after the S.O.S signal is gone and the DNA is repaired. Possible application Detecting DNA damage

  15. Quorum sensing - the way bacteria communicate Quorum Sensing - a phenomenon whereby the accumulation of signaling molecules enable a single cell to sense the number of bacteria. Vibrio fischeri.

  16. Example 2 : population control luxI/luxR system – the engineered regulatory module You, Cox, Weiss & Arnold ( 2004 NATURE)

  17. Construction of the population control program Output module input Regulatory module Cells divide More I More R* More E Less E Less R* Less I Less cells

  18. Results : The system reaches a steady state Wt cells Programmed cells the cell density in the active programmed cell is 10 fold lower.

  19. Results : The killer protein concentration Programmed cells wt cells Concentration of the killer protein in the active programmed cell is 1000 fold higher

  20. summary • The unity of the genetic code allows us to transfer circuits between organisms • The properties of the output is determined by the characteristic of the network examples • DNA damage detecting circuit (example 1) • Population density control circuit (example 2)

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