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Stephen Quake Keynote: Single-molecule sequencing shows microbial diversity is greater than expected #ASMGM

Submitted by on May 26, 2010 – 2:05 pm

I’m blogging this week from the 2010 American Society for Microbiology General Meeting with my colleague Mary Canady. I’ll be covering the scientific sessions and sharing interesting developments in genetics, microbiology, and technology. You can also follow the #ASMGM hashtag on twitter for updates.

Sunday night kicked off the conference with a presentation from Stanford bioengineering professor Dr. Stephen Quake, founder of Helicos Biosciences. Dr. Quake attained a mild amount of fame for being the first person to sequence his own genome, as opposed to the multi-center effort that went into the Human Genome Project.

Dr. Quake’s company Helicos has dramatically reduced the time and cost for sequencing projects, broadly expanding the application reach of sequencing. Faster, cheaper sequencing puts genomes within the grasp of smaller research groups, so it’s no surprise that microbiologists have begun to use it to sequence their favorite subjects.

Because the Helicos instrument is so sensitive, it can actually get a sequence from as little as a single cell, so biologists have begun to sample the “sequence space” of interesting microbiological habitats. One such habitat is the termite gut. Termites have the unique ability to digest wood due to microorganisms resident in their gut, but what Dr. Quake’s collaborators found is that it’s not just one species, but as many as 13 species are present, based on sequences recovered from gut samples. Knowledge of the different species living in this habitat can be used to develop new termite-resistant building materials, but just the fact that 13 different species are found in the gut of this tiny little creature was enough to impress the crowd here. Even more interestingly, it seems that the functions of the microbes are non-overlapping, so it’s no accident all these species are there, rather they serve as a form of evolutionary insurance for the termite. Even though one species would have been enough, having multiple species allows the termite to survive habitat changes that might have been less compatible with the resident bacteria.

As with the sequencing of his own genome, the technical details behind this effort are likewise fascinating (if you ask me, the engineering details nearly put those next to me to sleep). The key advance to make the sequencing work is the applicability of the technique to very small samples, such as you might be forced to work with if you wanted to study a bacteria found in nature that no one has yet learned how to cultivate in the lab. To work with samples in the nanoliter range, they developed an ingenious tiny valve controlled by overlapping expandable microchannels. Inflating one set of tubes would expand the wall into the adjacent tube, shutting of the flow of the adjacent channel. Printing complex patterns via lithography allowed them to sample, mix, and separate volumes small enough to contain a single bacterium. Next, they had to solve the problem of off rates, which are a fundamental limitation to how miniaturized an assay can be. They solved this by using a clear polymer to trap the solution over the assay surface, vastly reducing the volume into which the dye could diffuse.

Speaking before Dr. Quake was Yoshi Kawaoka, describing the synthesis of 1918 flu in the lab, technical advancement that aids the study of modern pandemic flu by comparison with this older, more deadly strain. Further work by Dr. Kawaoka led to the development of a novel neuraminidase inhibitor with activity against pandemic H1N1.

[Disclosures: Dr. Gunn is a San Diego-based scientific consultant and academic community liaison for Mendeley. Former clients include a private single molecule sequencing startup.]

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