DOE-OBER Workshop on New Frontiers in Characterizing Biological Systems

1. Office of Science Office of Biological and Environmental Research DOE-OBER Workshop on New Frontiers in Characterizing Biological Systems Arthur M. Katz Office of Biological & Environmental Research September 1, 2009 arthur.katz@science.doe.gov

2. Workshop Purpose • Identify new tools and analytical approaches for characterizing cellular and multicellular level functions and processes that are essential for developing solutions for DOE missions in biofuels, carbon cycle, low dose radiation and environmental stewardship Department of Energy • Office of Science • Biological and Environmental Research Department of Energy • Office of Science • Biological and Environmental Research 2Characterization

3. Workshop Scope • What are the biological/environmental processes we need to understand? • What are the limitations of current technology in addressing these needs? • What technical capabilities do we need to answer these most urgent scientific questions? 3Characterization Department of Energy • Office of Science • Biological and Environmental Research

4. Workshop Logistics • May 13–14, 2009 • Bethesda, Maryland • Agenda: - Plenary presentations on Science Needs - Three parallel breakout sessions - Report Out by Breakout Co-chairs 4Characterization Department of Energy • Office of Science • Biological and Environmental Research

5. Workshop Participants Mary Helen Barcellos-Hoff New York University School of Medicine Allen Bard The University of Texas at Austin Carl Batt Cornell University Talapady Bhat National Institute of Standards and Technology Federica Brandizzi Michigan State University Liaohai Chen Argonne National Laboratory Graham Cooks Purdue University Stephen Cramer University of California, Davis Brian Davison Oak Ridge National Laboratory Mitchel Doktycz Oak Ridge National Laboratory Mark Ellisman University of California, San Diego Wolfgang Fink California Institute of Technology Bruce Fouke University of Illinois Jim Fredrickson Pacific Northwest National Laboratory Paul Gilna University of California, San Diego Elizabeth Haswell Washington University, St. Louis Lynn Hlatky Tufts University School of Medicine Hoi-Ying Holman Lawrence Berkeley National Laboratory Phil Hugenholtz Lawrence Berkeley National Laboratory / JGI 5Characterization Department of Energy • Office of Science • Biological and Environmental Research

6. Workshop Participants, continued Rob Knight University of Colorado, Boulder Stephen Lane University of California, Davis Jan Liphardt Lawrence Berkeley National Laboratory John Markley University of Wisconsin-Madison Lisa Miller Brookhaven National Laboratory Robert Murphy Carnegie Mellon University Colin Murrell University of Warwick Dean Myles Oak Ridge National Laboratory George Patterson National Institutes of Health Piero Pianetta SLAC National Accelerator Laboratory Tijana Rajh Argonne National Laboratory Gary Sayler University of Tennessee Patricia Sobecky University of Alabama Alfred Spormann Stanford University Gary Stacey University of Missouri Jonathan Sweedler University of Illinois at Urbana-Champaign Kenneth Taylor Florida State University Daniel van der Lelie Brookhaven National Laboratory Tuan Vo-Dinh Duke University Matthew Wallenstein Colorado State University Steve Wiley Pacific Northwest National Laboratory 6Characterization Department of Energy • Office of Science • Biological and Environmental Research

7. Breakout Sessions • Cellular processes – Jonathan Sweedler/ Patty Sobecky - electron transport, energy production • Multicellular processes – Federica Brandizzi/ Mary Helen Barcellos-Hoff - biofilms, termite gut, microbial communities, tissue radiation responses • System interface processes – Mitch Doktycz/ Phil Hugenholtz - plant/microbe, microbe/mineral, molecular machine/materials 7Characterization Department of Energy • Office of Science • Biological and Environmental Research

8. Questions for the Breakouts What are the most significant scientific challenges in your field of research, and what information would you need to make significant advances? Are there promising tools and technologies to address these information gaps? What approaches or technologies would represent breakthroughs? Are there specific questions that require information developed at more than one scale (subcellular, cellular, multicellular, organism) in order to provide adequate understanding? What types of approaches are available or needed to connect information across the various scales? 8Characterization Department of Energy • Office of Science • Biological and Environmental Research

9. Representative Technologies • High-throughput genomic approaches for rapid single-cell characterization • Super-resolution optical spectroscopy at the nanometer scale • New nongenomic fluorescence probes • Electrochemical imaging • Novel isotope technologies including subcellular tracer studies • Nuclear magnetic resonance • Synchrotron-based approaches including X-ray fluorescence and tomography • Electron microscopy • Atomic force microscopy at the molecular scale • Secondary ion mass spectrometry on the nanoscale • Mass spectrometric metabolomics and proteomic approaches for global characterization 9Characterization Department of Energy • Office of Science • Biological and Environmental Research

10. Outcome: Four Major Technology Needs for Understanding Biological Function • Adding dimensions to biological measurements - Measuring simultaneously multiple chemical species/biological components and fluxes with appropriate temporal and spatial resolution - Creating multi modal measurements with spatial and temporal registration - Linking molecular to cellular to multi-cellular to environmental scales 10 Characterization Department of Energy • Office of Science • Biological and Environmental Research

11. Current Capabilities and Future Achievement Currently we can localize in the microbe target molecular species with high resolution. • What we need: • The physical location of the target microbe in its biological and abotic environment • Flux measurements of molecules in and out of the target cell • Quantified levels of specific proteins, RNA transcripts and metabolites in the target microbe at several time points 11 Characterization Department of Energy • Office of Science • Biological and Environmental Research

12. Outcome: Four major technology needs for understanding biological function • Adding dimensions to biological measurements - Measuring simultaneously multiple chemical species/biological components and fluxes with appropriate temporal and spatial resolution - Creating multi modal measurements with spatial and temporal registration - Linking molecular to cellular to multi-cellular to environmental scales • Identifying important events in heterogeneous environments - Measuring and associating rare events or minority components to functional outcomes. - Identifying and detecting single or small populations of molecules or cells amidst complex heterogeneousbackgrounds Department of Energy • Office of Science • Biological and Environmental Research 12Characterization

13. Outcome: Four major technology needs for understanding biological function, continued • Completing the “parts-list”—Seeing it all - Capturing of cellular components, e.g. metabolites and carbohydrates, that are currently invisible or poorly characterized - Manipulating the activity of these poorly characterized components to understand their functional significance • Integrating information for predictive understanding - Creating tools for the integration and interpretation of complex data sets - Developing databases and computational approaches for integrating measurements and models at multiple scales. - Constructing iterative feedback systems between experiment and modeling 13Characterization Department of Energy • Office of Science • Biological and Environmental Research

14. Workshop Report Currently completing the workshop report and executive summary • Substantial written materials produced by the working groups have been organized and integrated • Co-Chairs and other participants have had regular telephone conferences to review drafts of sections of report • Final version of the report is under way. 14Characterization Department of Energy • Office of Science • Biological and Environmental Research

15. Report schedule • Target date for completion of final draft of the report is September 30, 2009 • Report is expected to be posted by October 15, 2009 on http://www.sc.doe.gov/ober/BER_workshops.html 15Characterization Department of Energy • Office of Science • Biological and Environmental Research

16. Workshop leadership • External co-chairs • Jonathan Sweedler, University of Illinois at Urbana-Champaign • Patricia Sobecky, University of Alabama • Federica Brandizzi, Michigan State University • Mary Helen Barcellos-Hoff, New York University • Mitch Doktycz, Oak Ridge National Laboratory • Phil Hugenholtz, Joint Genome Institute • BSSD Division • Drs Arthur Katz and Dean Cole 16Characterization Department of Energy • Office of Science • Biological and Environmental Research