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Making Sense of the Microbial World

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Gautam Dantas
Title: Assistant Professor, Washington University School of Medicine
Education: PhD, University of Washington, 2005
Recommended by: George Church

Gautam Dantas' lab has two distinct research targets in its sights that use genomic technoloies to elucidate the microbial world. One is biofuel discovery, where Dantas is looking at ways to improve metagenomic library construction and the application of functional selections for the production of alternative fuels from plant biomass. He is using both culture-based and culture-free functional metagenomic approaches to find candidate biofuel producing strains. Dantas is also using next-generation sequencing and computational tools to help identify and tweak the molecular structures and functions of gene products.

The other focus of his research is investigating antibiotic resistance. "We're getting to the point where, surprisingly, infectious disease mortality rates are beginning to increase again — something that we thought was a solved problem — but in the last century, we're seeing that people are dying more and more from infections that are not curable," Dantas says. "One of the big questions is that if disease-causing pathogens are getting more resistant to chemicals, how are they doing that?" To help answer this question, Dantas is utilizing whole genome sequencing, transponson mutagenesis, culturing independent metagenomic selections, and a range of biochemical and structural analysis methods to understand antibiotic metabolism and resistance at the molecular level.

Dantas was originally trained in David Baker's lab at the University of Washington where he worked primarily on computational protein design and a lot of protein structure. But by the time he arrived at George Church's lab at Harvard University, he was interested in applying new technologies to look at microbial communities. And although biofuels and antibiotics resistance projects didn't exist in the Church lab when he first arrived, this was merely a mild bump in the road. Dantas soon learned that the Church lab was not a place for where limitations and convention were acceptable. "One of the beauties of being in the lab is that George says 'if you come up with a crazy idea, all I will say is think a little crazier,' and I was infected by that approach to doing to science," he says.

The long-term goal of his biofuel research is to improve methods for functional metagenomics to take specific functions, such as tolerance to inhibitors, that are encoded in metagenomes and convert them into accessible fragments in engineered organisms. "In five years, I would like to be able to take any phentoype you are interested in and give you a platform where you can have plug-and-play engineering where you can input your metagenomic DNA and get out the functional parts which are compatible with some arbitrary host," he says.
On the antibiotic resistance side, Dantas would like to fundamentally understand how much antibiotic resistance is out there in the world, in terms of genes. "Right now, we've just begun to scratch the surface. One of the big questions we want to answer is not just what's out there, but what is the likelihood of that ending up in pathogens?" he says. "We want to find out if we can make any difference in the way we give antibiotics to kids and adults and how we dump antibiotics into the environment."

Publications of note

In August 2009, Dantas published a paper in Science entitled "Functional characterization of the antibiotic resistance reservoir in the human microflora." In it, he and his team functionally characterized the resistance reservoir in the microbial flora of healthy individuals in order to elucidate the process through which antibiotic resistance genes are acquired by human pathogens.

And the Nobel goes to...

Dantas would like to accept his prize for either making a discovery that addresses poverty or for supporting evolutionary theory and showing how important evolution is, and always will be, for any part of science.

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