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by Maggie Zhang
Graduate student in the Committee on Microbiology

In 1683, a Dutch merchant named Leeuwenhoek built his own microscope and focused it on some residue he found on his teeth. What he saw prompted him to fire off a letter to the Royal Society of London, describing the “animalcules” he realized were living in his mouth.

We now appreciate that these microbial creatures are everywhere on Earth, thriving even in hostile environments the likes of which other animals could never tolerate—underneath Antarctic glaciers, within bubbling asphalt lakes, inside hydrogen sulfide gas caves. Some, like Leeuwenhoek’s “animalcules,” grow just fine in the presence of oxygen; other “anaerobes” can’t tolerate air at all.

Bacteria are important members of every ecological niche. We like to give plants all the glory for producing the oxygen necessary for life, but photosynthetic marine and freshwater inhabitants actually produce half of the oxygen we breathe. Meanwhile, bacteria living in the soil are often model citizens, breaking down nature’s waste to obtain nutrients for themselves and recycling the rest into building blocks for new life. What’s more, the human gastrointestinal tract houses over three pounds of bacteria that break down our food and provide us with essential vitamins.

With the fundamental roles that microbes play in our daily lives, it’s important for us to understand them. But how do you physically and genetically dissect something so small?

Scientists initially solved this problem by growing individual strains of bacteria in rich broths to study their biological properties, including their DNA. Soon enough, they ran into a roadblock: less than 1 percent of the bacteria on Earth could be easily cultivated. Studying the other 99 percent was going to require some new tools.

Thus, the field of metagenomics was born. Metagenomics technologies allow us to directly sequence the entire genetic contents of all microbes living within a habitat.

Unfortunately, sequencing the collective genetic makeup of even a 2,000-member community means several million DNA fragments. Although accurately piecing them back together into coherent genomes provides essential insights to microbiologists, the task is not much different than simultaneously assembling 2,000 jigsaw puzzles with all the pieces mixed into one huge pile.

Yikes.

A. Murat Eren, PhD—known to colleagues as Meren—and his team at the University of Chicago are at the frontier of developing the computational tools necessary for this daunting task. They have created several flexible, open-source software packages that allow users to dig deep into their data while retaining command of their analysis. These tools enable scientists to reconstruct novel microbial genomes from environmental samples, study their evolutionary relationships to other organisms, and investigate their abundance and distribution, as well as their functions. Collectively, the approach can tell us a lot about the biological traits important for a given microbe to survive and promote various environmental conditions, including health and disease.

In 2015 Meren and his team launched anvi’o, an advanced analysis and visualization platform. Using this software, scientists can ask a wide range of questions about the metagenomes they are studying through a highly intuitive, fully customizable interactive interface. The team has produced many highly comprehensive tutorials for users.

Anvi’o has already been cited by more than 50 publications, ranging from studies characterizing the human microbiome to articles debating the origins of humankind. Meren and his team make the software freely available online, for researchers all over the world.

At UChicago and affiliated labs at the Marine Biological Laboratory in Woods Hole, Massachusetts, and at Argonne National Laboratory, Meren’s tools are helping colleagues re-envision the future of microbiome research. Scientists are using the tools to study the use of antibiotics during pregnancy, fight serious infections, understand gut inflammation, and even survey oral “animalcules” much like those Leeuwenhoek saw in his mouth centuries ago.

This research would be impossible without scientists like Meren who also excel in computational technologies. With outstanding tools at the centerpiece of the efforts, these collaborative efforts will help us gain knowledge about the microbiome, which will improve health for millions.

As it has been through eons of human history, scientific discovery and tool development are like the chicken and the egg, totally dependent on each other. But Meren and his team put the scientific chicken first: “Although the inherent link between the tool and thinking will continue to bind them together, we believe it must be mostly the intellectual curiosity that drives the direction of science, and not the comfort of what is available. We intend to maintain our flexibility, and let the incoming questions shape and re-shape our software.”