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The astonishing world of microbes has lots to teach us

And with two major foundation grants, CU-Boulder prof is on the case

Rob Knight is widely recognized as a leader in the burgeoning field of microbial research.



By Jeremy Simon and Clint Talbott

Microbes are hot in certain circles these days. Just ask your cheese-making or beer-brewing neighbors, each of whom rely on and manipulate microbial processes to generate their desired edible or quaffable.

The ramifications of microbes extend much further than artisan food and drink. And though they are the most abundant species on Earth
and play vital roles in all ecosystems, most remain uncharacterized.

A deep study of microbial taxonomy and geography can help us better understand—and sustainably adapt to—a broad array of processes essential to human and animal habitats as well as fundamental ecological principles and processes.

CU-Boulder is a lead player in an unprecedented worldwide effort to characterize and catalog microbes, known as the Earth Microbiome Project. Early this year, the university was awarded two major grants, a $1 million grant from the W.M. Keck Foundation and a $950,000 grant from the Templeton Foundation.

Together, these grants will advance the distinctive and novel research underscoring the Earth Microbiome Project.

Project marshals diverse CU expertise

CU BioFrontiers faculty member Rob Knight, professor of chemistry and biochemistry, was principal investigator on these two grants,
and numerous other CU-Boulder personnel are making fundamental contributions to this project.

For example, Assistant Professor Valerie McKenzie of ecology & evolutionary biology has played a lead role that has led to the securing of the Templeton Foundation grant, and contributes key animal microbiome expertise.

These CU contributors span
varied disciplines. Manuel Lladser in applied math and Aaron Clauset of computer science contribute advanced statistical modeling techniques and network science. Robin Dowell of molecular, cellular, & developmental biology contributes expertise in sequence assembly.

Ryan Gill of chemical & biological engineering contributes expertise in functional annotation. And students, especially those receiving training through
the Interdisciplinary Quantitative Biology (IQBio) program, play a key role advancing the Earth Microbiome Project.

Much of this work builds on the findings and groundwork of CU-Boulder biology Professor Norman Pace, one of eight CU faculty members to have won a MacArthur Fellowship.

Knight is widely recognized as a leader in the burgeoning world of microbial research. The New Zealand native publishes peer-reviewed journal articles at a dizzying pace and combines emerging knowledge in microbiology with significant advances in super-computing. In May, Knight was a primary subject for a New York Times magazine cover story, “Some of My Best Friends Are Germs.”

He has even made a splash
in popular culture. In 2010, the television program CSI: Miami depicted a technique Knight assisted in developing (with CU-Boulder Professor Noah Fierer) to match bacterial keyboard fingerprints with people who left the telltale microbes behind.

Tiny microbes can help answer big questions

The roughly 100 trillion microbes in the human body substantially exceed the number of cells in that same body. Yet while microbes are small, they play a big role in a wide variety of processes, including carbon cycling, nutrient cycling, climate change, water purification, agricultural productivity, and animal and plant health.

“What we don’t know is how
they all work together, how they’re distributed,” Knight says. The Earth Microbiome Project may lead to insights related to each of these questions.

For example: How does land-use policy change how microbes
look in the longer term? How do microbes change the productivity
and biodiversity of plants? How can microbes be better harnessed for water purification purposes? Perhaps, Knight suggests, microbes we now think of
as pathogens could have previously unrecognized positive benefits.

The feasibility of this research
has dramatically improved in recent years, thanks to DNA-sequencing- technology advances that sharply increase productivity and reduce sequencing cost. CU-Boulder’s
new Jennie Smoly Caruthers Biotechnology Building was designed in part to facilitate state-of-the-art technology (such as these sequencing capabilities) not previously available or optimized at CU-Boulder.

A truly global collaboration

The structure of this highly dispersed project is itself distinctive.

First, Knight and his colleagues seek to characterize, spatially and temporally, tens of thousands of microbial communities. Online social networks have helped to organize sample collection and coalesce project communications and activities amongst hundreds of collaborators at 125 different labs, whose combined expertise spans ecology, mathematics, molecular biology, computer science, engineering, and other fields. (Knight is no stranger to novel uses of social networks, having using a grass-roots crowdfunding mechanism to raise $340,000 for an open-source research study into the effects of diet on gut bacteria.)

Next, Knight’s group aims to develop new methods for higher-throughput sample-handling, DNA extraction, and library construction, including illuminating often- neglected taxa such as microbial eukaryotes and viruses, for deeper insight into community dynamics.

The researchers then aim to develop computational strategies that solve major hurdles to effectively analyzing such vast data sets, including predictive modeling, network analysis, and multi-scale data integration.

“We will thus enable a broad range of research in microbial ecology, provide novel platforms for testing ecological theories, and improve public understanding of the importance of microbial life,” Knight says.

Knight says research of the experimental, high-impact nature funded by the Keck and Templeton foundations is not typically supported by more traditional federal funding agencies such as the National Science Foundation. “They’re particularly excited about funding projects that other agencies might not fund because they’re too risky or too innovative or too far beyond the scope of typical science research,” he says.

Even this new study, however, will only scratch the surface of microbial diversity, Knight says. “We will be able to build a framework describing how microbial communities are assembled and change,” he says. “But there is
so much more than could be done
to integrate new systems into that framework.”

To support the Earth Microbiome Project, contact 303-735-0973.