All entries for Monday 26 June 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:

• emerging coherence Chemical oscillators: Kiss Science 2002
• Repressilator coupled by quorum sensing, Garcia-Ojalvo PNAS 2004 and McMillen PNAS 2002

Part two: Phase singularities in circadian clocks:

: 26 Jun 2006 20:11 |  Comments (0) |  Close comments |  Report a problem

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

: 26 Jun 2006 18:26 |  Comments (0) |  Close comments |  Report a problem

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

: 26 Jun 2006 12:03 |  Comments (0) |  Close comments |  Report a problem