The New Science of Metagenomics:Revealing the Secrets of the Microbial Planet

Committee on Metagenomics: Challenges and Functional Applications

Jo Handelsman, Co-Chair, University of WisconsinJames M. Tiedje, Co-Chair, Michigan State UniversityLisa Alvarez-Cohen, University of California, BerkeleyMichael Ashburner, University of CambridgeIsaac K. O. Cann, University of Illinois, Urbana-ChampaignEdward F. DeLong, Massachusetts Institute of TechnologyW. Ford Doolittle, Dalhousie UniversityClaire M. Fraser-Liggett, The Institute for Genomic ResearchAdam Godzik, The Burnham InstituteJeffrey I. Gordon, Washington University School of MedicineMargaret Riley, University of Massachusetts, AmherstMolly B. Schmid, Keck Graduate Institute

NRC STAFFFran Sharples, Director, Board on Life SciencesAnn Reid, Study Director Anne Jurkowski, Senior Program Assistant

Funded by: NSF, NIH and DOE

What is Metagenomics

A new science that seeks to understand biology at the aggregrate level, transcending the individual organism to focus on the genes in the community and how they interact to serve a collective function.

It is both a set of research techniques AND a research field.

It is the science of (microbial) communities. Metagenomics will be the systems biology of the biosphere.

A Vast FrontierDiversity, Opportunity, Challenge,

Timeliness• The microbial world is incredibly diverse and

largely unknown.

• What we do know shows that microbes determine the health of the planet and its inhabitants.

• Metagenomics provides the tools to explore the new frontier and to solve problems important to humankind.

• The time is now; we have the technology, knowledge base and the questions to begin.

The Indispensable Microbial WorldMicrobial Services

– Homeostasis of the biosphere– Agriculture – crop and animal productivity and health– Industrial processes, waste treatment, bioremediation– Bio-based energy - from production to product– Biotechnology – pharmaceuticals, enzymes,

biomolecules, bioconversions– Human health – colon cancer, esophageal cancer, heart

disease, HDL/LDL, Turette Syndrome, obesity, periodontal disease

– And our surrounding environment: The air we breathe, the water we drink, our food, and the synergies among their microbes and ours, and the environment we provide them.

A new light on biology – The Big Questions

Microbes live in concert with every higher organism on Earth, often to their benefit but sometimes not.

Unifying theories in biology are not possible without understanding more than a snippet of the microbial world.

A new light on biology: Big Questions

Exploring the microbial world may transform our understanding of biology– How diverse is life?– What is a species?– How do microbial communities affect their

hosts? – How do microbial communities work?– How do they react to change?– What governs community robustness?– How do microbes evolve?

Metagenomics Challenges• Sampling & metadata• Functional analysis, HTP technologies• Data access, management & analysis

- metadata standards and their integration- the impending data deluge- a different kind of sequence: annotation, patterns,assembly- specialized databases, community curation, metadata queries- new analysis tools, robust software

• Post-sequence science• Institutional issues

- interagency coordination, e.g. centralized infrastructure- international coordination, communication, efficiencies- intellectual property, CBD, data release

• Training, new combinations of knowledge

Our Recommendation: A Global Metagenomics

Initiative• Large-scale projects

– spur new technologies, tools, attract broad expertise.– explore community science in greatest depth.– provide basis for unifying theory.– capture the public imagination.

• Medium-scale projects– engage inter-disciplinary teams.– explore a greater breadth of important microbial

communities and questions.• Small-scale projects (PI projects)

– explore an even greater diversity of habitats, questions or add depth to an above study.

– attract new creative ideas and diverse talent to the metagenomic effort.

– engage the broad research community

Metagenomics - Seize the future

• GMI - Multi-scale funding, many habitats• Develop theoretical framework from the top

down and bottom up• Meet the data challenge, the first bottleneck• Train new talent, in new ways, the next

generation metaG student• Engage the public• Develop the effective institutional and scientific

community coordination

A Vast FrontierDiversity, Opportunity, Challenge,

Timeliness• The microbial world is incredibly diverse and

largely unknown (0.1%? 0.001? cultured)

• What we do know shows that microbes determine the health of the planet and its inhabitants (1/2 the biomass of Earth)

• Metagenomics provides the tools to explore the new frontier and address practical problems

• The time is now.

Ghana short season maize vs mucuna

Brazilian rainforest yesterday and today

The New Science of Metagenomics:

Revealing the Secrets of the Microbial Planet