Combinatorial genomics

I have recently become addicted to the TED talks. I caught the TED talk by Craig Venter on various projects stemming from the initiatives undertaken by the Venter Institute and his affiliated companies. One of the exciting things he talked about was the coming field of combinatorial genomics (CG). CG is basically a marriage between synthetic biology and genomics. Basically it will deal with creating “synthetic” life forms with desired properties that are obtained by screening a library of such microbes obtained from combining genes from a multitude of organisms.

This is of course possible given the following five technologies.

Knowledge of a minimal subset: Work on the “minimal genome project” resulted in the minimal set of genes required to have a living reproducing bug or virus.

The ability to synthesize large amounts of large DNA :In his talk Craig Venter talked of their work in synthesizing the genome of Phi-X174 fully in two weeks.

The final piece of the puzzle comes from being able to assemble stretches of synthesized DNA quickly and combinatorially from these pieces. Here the amazing bug deinococcus radiodurans comes to the rescue. Deinococcus radiodurans is able to re-assemble its genome thousands of small bits which result from very harsh radiation or severe drying. Exploiting its mechanism to achieve this amazing feat its should be entirely possible to fully reconstitute an intact genome from a multitude of pieces.

The final piece of the puzzle of course is the genomics toolset itself. It is possible to assemble specialized subsets for any desired function by comparing genomes that carry out a particular function with closely related ones that do not.

So given all this,  Craig Venter talks of assembling million chromosomes per day and transplanting these into cells or synthetic cells and screen for a desired effect. This he dubs as the emerging field of combinatorial genomics. A few of these desired functions are the stuff of biotechs promise since its inception: making hydrogen from photosynthetic bacteria, digesting cellulose to make ethanol and making small molecules by metabolic pathway engineering.

There is more on the technological aspects of combinatorial genomics at syntheticgenomics.com , one of Craig Venters companies. The TED talk above is also an excellent listen.

Other resources:

The Nature podcast section on deinococcus radiodurans and mp3 file