…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
- Building synthetic gene networks: Gene toggle and RNA swithces
- Applications in microbiology: (anti)toxins and cell death pathways
- 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 unpublished at the time.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
- Mammalian Systems
- Network based drug development
- Multi–scale approaches