All entries for Monday 26 June 2006

June 26, 2006

Synthetic Biology III

Follow-up to Synthetic Biology talks II from Schreibfaul in Warwick

Talk by Strogatz

Title: "Synchronization, singularities and circadian clocks: lessons from Art Winfree's pre–molecular approach to systems biology"

Part one: Synchronization:

Coupled ocillators in experiment:

Part two: Phase singularities in circadian clocks:

Synthetic Biology talks II

Follow-up to Synthetic Biology from Schreibfaul in Warwick

Title: "Programming bacteria: wiring synthetic sensors and circuits to heterologous outputs"

talk by Christopher Voigt

Three systems in E.Coli:

  1. Light Sensor Nature 2005
  2. Heat Sensor
  3. Logic Gate. in progress. previous Leiber Science2002

Programming Bacteria:

  • Competition 6 month time limit. iGEM Genetic Engineering Competition
  • a national student competition

One: Light Sensor:

  • Bacterial Photography. Change gene expression on light.
  • on known photoreceptors in E.coli. just in other organisms.
  • Phytochromes in Cyanobacteria, Arabidopsis.
  • kinase that is activated on light induction
  • compine e.coli osmotic shock sensor with cph1, ouput lacZ

Two: Bacterial Thermometer:

  • Heat shock and Cold shock repsonse promoters
  • Cold: Hypb, ansb, cspa_x promoter
  • Heat: htpG

Synthetic Logic (AND gate):

  • Examples of other gates in ecoli, yeast and mammal cells

Synthetic Biology

Follow-up to Group meeting: Boston and Jerusalem from Schreibfaul in Warwick

…and it comes back to haunt you. Need to make an overview of the Heidelber conference. Let's look at the Collins talk first :

Title: "Integrating synthetic biology and systems biology"
Collins, J. J., 20 Oct 2005

  1. Building synthetic gene networks: Gene toggle and RNA swithces
  2. Applications in microbiology: (anti)toxins and cell death pathways
  3. Inferring genetic networks: using the network model to infer the mode of action of drugs

To one. Synthetic gene networks:

  • Forward Engineering. Design switch, simple modeling,produce plasmids and see if it works. Gardner in Nature 2000. (Toggle switch in E.coli).
  • moving from e. coli up to yeast and mammalian systems. coupling to natural systems.
  • RNA based synthetic biology: Enginieered ribo–regulators. Issacs Nature Biotechnology 2004

To two. Applications in microbiology:

  • biosensors and programmable cells
  • wirkung von toxins. Afif 2001 CcdB
  • gradielles anschalten von toxins, antibiotics. following along the cell death pathway. iron comes in at later stage. unpublished at the time.

To Three. Infering genetic networks:

  • Reverse engineering gene networks
  • overexpress genes of interest, obtain expression profiles, feed into NIR algorithm, reverse engineer regulatory network
  • Yeung PNAS 2002 and Tegner PNAS 2003
  • Example with E Coli SOS pathway: Gardner Science 2003
  • 9 gene subnetwork. perturb gene expression. output by real time pcr. algorithm gives graphs, sign and strength of interaction.
  • next step: use result to find key players with most influence over the other genes. recA, lexA which confirms previous biological results.

  • Most exciting application: Infer the mode of action of compounds.
  • drugs: know drug hits some target. but: what else does that drug hit? difficult
  • now if you know the network and you know the output, you can infer what the input was.
  • test approach with the sos pathway by upregulating recA, lexA, measure output, run NIR and infer that recA, lexA was upregulated. horay.

  • up to higher organism. very costly to turn genes up or down. So you are only left with the output. hope is that by a lot of perturbations like drugs, mutations etc. might still infer network. Bernardo Nature Biotechnology 2005

*Future applications:"

  • Mammalian Systems
  • Network based drug development
  • Multi–scale approaches

Ulrich Janus

June 2006

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