Saturday, May 20, 2006

"Shotgun mapping of transcription regulation" - Timothy Gardner

Largely focused on network biology. Antibiotic development (IDed potentiators of cipro), bioenergy, and synthetic biology. In particular focusing on techniques to speed up determining what these networks look like. Techniques for characterizing metabolic networks are better developed than those for transcription.

The RS latch is the fundamental element in computer circuits. Why not implement it biologically? Construct a plasmid with two genes that cross-inhibit eachother... it worked, and others have built with it (Elowitz, Weiss, Simpson, the biophotographic film); it's been great.

But there's a problem - almost all these devices have been constructed with only two or three parts - the same two or three parts (Tet, CI, and LacI). Even if we have the capability to synthesize and assemble genetic systems of unlimited size, we don't have many parts to build with and there's way too much cross-talk with endogenous circuits. Maybe what we should focus on is how to interface with the existing "endogenous circuitry."

Shewanella oneidensis can serve as catalysts without mediators; they could potentially produce current from any carbon source: sugar, sewage, cellulose. But they don't produce alot of power... it takes a suitcase of bacteria to power a single portable electronic device.

One can find similar metabolic pathways, like those that could produce current in S oneidensis, through homology searches. How can we build genome scale transcription and translation models?

Fortunately, a database of expression and transcriptional controls exists for E. coli, which facilitated the creation of a mathematical model of genome-wide gene expression and transcriptional control based on Affymetrix microarray data. This model is driven by the CLR algorithm and based on analysis with mutual information instead of correlation.

The best way to identify the regulatory networks is to stress and test a given microbe in a great diversity of conditions, hence the term "Shotgun mapping."

"When I think about synthetic biology, I think it's more about the biology of synthesis, the synthesis of fuels, drugs, etc., and so I think it's important right now to focus on ways of understanding and controling existing biological circuits and machines." (paraphrased).

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