Office of Science

Office of Biological and Environmental Research

Joseph Graber, Ph.D. Program Manager, Genomic Science Program Team Lead DOE Office of Biological and Environmental Research

Overview for NAS Industrialization of Biology Committee

February 27th, 2014

DOE: Biological and Environmental Research

Department of Energy • Office of Science • Biological and Environmental Research 2 BER Overview

Biological and Environmental Research

Understanding complex biological, climatic, and environmental systems across vast spatial and temporal scales

The Scientific Challenges:

Understand how genomic information is translated with confidence to redesign microbes, plants or ecosystems for improved carbon storage, contaminant remediation and sustainable biofuel production

Understand the roles of Earth’s biogeochemical systems (atmosphere, land, oceans, sea ice, subsurface) in determining climate so we can predict climate decades or centuries into the future, information needed to plan for future energy and resource needs.

Department of Energy • Office of Science • Biological and Environmental Research 3 BER Overview

Biological and Environmental Research Approach • Understanding complex biological and environmental systems across

many spatial and temporal scales:

– From the sub-micron to the global

– From individual molecules to ecosystems

– From nanoseconds to millennia

• Integrating science by tightly coupling theory, observations, experiments, models, and simulations

• Supporting interdisciplinary research to address critical national needs

• Engaging national laboratories, universities, and the private sector to generate the best possible science

Department of Energy • Office of Science • Biological and Environmental Research 4 BER Overview

Biological and Environmental Research (BER)

Foundational Science - integrating observations and experimental capabilities with modeling for predictive understanding

Understand the effects of greenhouse gas emissions on Earth’s climate and biosphere

• World-leading capabilities in climate modeling

• Representation of clouds in climate models

• Direct/indirect effects of aerosols on climate

• Interactions of carbon cycle and climate

• Predictive understanding of terrestrial ecosystems, focus on sensitive systems, e.g., Arctic and tropics

Explore frontiers of genome-enabled biology

• Sustainable bioenergy resources

• Function & organization of plant and microbial systems

• Mechanisms and regulation of carbon storage in plant biomass and microbial communities

• Biosystems design

• Systems biology via data integration and analysis within a systems biology knowledgebase

Department of Energy • Office of Science • Biological and Environmental Research 5 BER Overview

Office of Science

Patricia Dehmer (A)

Advanced

Scientific

Computing

Research

Fusion

Energy

High

Energy

Physics

Basic

Energy

Sciences

Climate and

Environmental

Sciences

Gary Geernaert

Director

Biological

Systems

Science

Todd Anderson

Director

Biological and

Environmental

Research

Sharlene Weatherwax, AD

Nuclear

Physics

Background - BER

Department of Energy • Office of Science • Biological and Environmental Research 6 BER Overview

DOE Genomic Science Program

The major objectives of the Genomic Science program are to:

• Determine the molecular components, regulatory elements,

and integrated networks needed to understand genome-

scale functional properties

• Develop “-omics” experimental capabilities and enabling

technologies needed to achieve dynamic, systems-level

understanding of organism and/or community function

• Develop the computational capabilities, and modeling

capacity, and integrated knowledgebase to advance

predictive understanding and manipulation of biological

systems

DOE mission driven fundamental research

aimed at identifying the foundational systems

biology properties of microbes, plants, and

complex communities.

Department of Energy • Office of Science • Biological and Environmental Research 7 BER Overview

Genomic Science Program

Department of Energy • Office of Science • Biological and Environmental Research 8 BER Overview

BioEnergy Science Center (Oak Ridge National Lab)

• Overcoming biomass “recalcitrance” as route to cost-effective cellulosic biofuels

• “Consolidated Bioprocessing” – one-microbe / community to go from plants to fuel

Great Lakes Bioenergy Research Center (U Wisconsin, Michigan State)

• Re-engineering plants to produce more starches and oils

• Using HTP technologies to optimize chem/bio process for biomass deconstruction

• Sustainability of biofuels

Joint BioEnergy Institute (Lawrence Berkeley National Lab)

• New pretreatment process using room temperature ionic liquids

• Beyond cellulosic ethanol: re-engineering E.coli and yeast to produce hydrocarbons – goal of “green” gasoline, diesel, jet fuel

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The DOE Bioenergy Research Centers

New paradigm for research—single focus, multi-disciplinary, team-based Transformational science Rigorous DOE management and progress review against milestones

Department of Energy • Office of Science • Biological and Environmental Research 9 BER Overview

www.genomicscience.energy.gov/

biosystemsdesign/

Biosystems Design for Biofuels Production

DOE Research Areas:

• Microbial Systems Design: Iterative

network and functional measurements,

computational modeling, and genome-

scale engineering to design new

microbial systems for the production of

advanced biofuels

• Plants Systems Design: Integrative

systems biology and large-scale

genome engineering approaches to

deconstruct cell walls and convert them

into advanced biofuels

Department of Energy • Office of Science • Biological and Environmental Research 10 BER Overview

www.kbase.us

DOE Systems Biology Knowledgebase (KBase) Building a Community Resource for Predictive Biology

KBase offers a unified environment for users to view, query, and download data for microbes, plants, and microbial communities. Users can apply a series of powerful demonstration workflows, including genome annotation, metabolic modeling, and phenotype analysis.

Integration across microbes, communities, and plants will enable the

construction of models ranging from the genotypes of complex microbial and plant communities to their phenotypes, enabling researchers to optimize solutions for bioenergy or the environment.

Systems biology data, models, and information

currently integrated for genomes of 5534 unique prokaryotes, 161 archaea, and 175 eukaryotes.

Efforts continue to integrate microbial and plant genomic, proteomic, and transcriptomic data sets from DOE research

Department of Energy • Office of Science • Biological and Environmental Research 11 BER Overview

Biological and Environmental Research (BER)

Scientific User Facilities

Environmental Molecular Sciences Laboratory (EMSL) - providing integrated experimental & computational resources for discovery and technological innovation

Joint Genome Institute (JGI) - meeting the DNA sequencing needs of the bioenergy, carbon cycle, and biogeochemical science communities

Atmospheric aerosols

Nanosized battery

Modeling contaminants

Fungal ligninase

Poplar

Atmospheric Radiation Measurement (ARM) Climate Research Facility - providing continuous field measurements and data products to improve cloud and aerosol science in climate models

Department of Energy • Office of Science • Biological and Environmental Research 12 BER Overview

• Genome Scale Engineering Tools

HTP gene editing/recoding technologies

Improved integration of large synthetic DNA

constructs

Tools for incorporation of synthetic amino acids etc.

• DNA Synthesis and Assembly

Technologies for cost effective, high efficiency

synthesis and assembly of large DNA constructs

• Biosystems Analysis & Tuning:

Tools for high resolution, high throughput

measurement, analysis, and interpretation of the

metabolic and regulatory networks

Improved “wiring diagrams” of manipulated

organisms

Iterative approaches for subsequent “tuning” of

modified pathways

Biosystems Design: Needs in Methods & Technologies

Department of Energy • Office of Science • Biological and Environmental Research 13 BER Overview

• Advanced Biological Design Principles

Understanding foundational principles governing living

systems to improve directed bioengineering, defining the

“solution space” available to designers and suggesting

new approaches.

• Expansion of Genetically Tractable Organisms/Chassis

Extension of synthetic biology tools to a more diverse set

of organisms would provide a broader array of functional

capabilities and growth characteristics

Expanded tools and techniques for plant systems

• Development of Minimal Cell and in vitro Systems

Minimal cell systems (i.e., highly streamlined platform

organisms) or cell free in vitro systems; fully defined

pathways and functional components

• Biocontainment Mechanisms

Tools and methods for assessment of risks associated

with synthetic constructs and incorporation of redundant

safeguards at successive levels of design, build, test,

extend, and manufacture.

Biosystems Design: Needs in Platform Development

Department of Energy • Office of Science • Biological and Environmental Research 14 BER Overview

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• Computational Tools & BioCAD Systems

Expanded tools to accommodate a wider

suite of biological parts and platform

organisms

Facilitate in silico design of synthetic parts

and systems

Develop efficient workflows for

construction and experimental validation

of large numbers of genetic design

variants

• Information Standards and Databases

Development of shared minimum

information standards and bioinformatic

databases to facilitate the sharing of data

that is of known quality, fully transferrable,

and properly curated

Biosystems Design: Computational Tools & Bioinformatics

Department of Energy • Office of Science • Biological and Environmental Research 15 BER Overview

For more information:

DOE-BER: www.science.energy.gove/BER/

Genomic Science Program website: www.genomicscience.energy.gov

Joseph Graber: joseph.graber@science.doe.gov

Pablo Rabinowicz: pablo.rabinowicz@science.doe.gov

Todd Anderson, Director, Biological Systems Science Division

todd.anderson@science.doe.gov

Office of Science

Office of Biological and Environmental Research

Thank you!

Joseph Graber

Joseph.Graber@science.doe.gov

http://science.energy.gov/ber