DOE-OBER Workshop on New Frontiers in Characterizing Biological Systems

DOE-OBER Workshop on New Frontiers in

Characterizing Biological Systems

Arthur M. Katz

Office of Biological & Environmental Research

September 1, 2009

[email protected]

Office of Science

Office of Biological and Environmental Research

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 ResearchDepartment of Energy • Office of Science • Biological and Environmental Research2 Characterization

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?

Department of Energy • Office of Science • Biological and Environmental Research3 Characterization

Workshop Logistics

• May 13–14, 2009

• Bethesda, Maryland

• Agenda:

- Plenary presentations on Science Needs

- Three parallel breakout sessions

- Report Out by Breakout Co-chairs


Workshop Participants

Mary Helen Barcellos-Hoff New York University School of MedicineAllen Bard The University of Texas at AustinCarl Batt Cornell UniversityTalapady Bhat National Institute of Standards and TechnologyFederica Brandizzi Michigan State UniversityLiaohai Chen Argonne National LaboratoryGraham Cooks Purdue UniversityStephen Cramer University of California, DavisBrian Davison Oak Ridge National LaboratoryMitchel Doktycz Oak Ridge National LaboratoryMark Ellisman University of California, San DiegoWolfgang Fink California Institute of TechnologyBruce Fouke University of IllinoisJim Fredrickson Pacific Northwest National LaboratoryPaul Gilna University of California, San DiegoElizabeth Haswell Washington University, St. LouisLynn Hlatky Tufts University School of MedicineHoi-Ying Holman Lawrence Berkeley National LaboratoryPhil Hugenholtz Lawrence Berkeley National Laboratory / JGI


Workshop Participants, continued

Rob Knight University of Colorado, Boulder

Stephen Lane University of California, Davis Jan Liphardt Lawrence Berkeley National LaboratoryJohn Markley University of Wisconsin-MadisonLisa Miller Brookhaven National LaboratoryRobert Murphy Carnegie Mellon UniversityColin Murrell University of WarwickDean Myles Oak Ridge National LaboratoryGeorge Patterson National Institutes of HealthPiero Pianetta SLAC National Accelerator LaboratoryTijana Rajh Argonne National LaboratoryGary Sayler University of TennesseePatricia Sobecky University of AlabamaAlfred Spormann Stanford UniversityGary Stacey University of MissouriJonathan Sweedler University of Illinois at Urbana-ChampaignKenneth Taylor Florida State UniversityDaniel van der Lelie Brookhaven National LaboratoryTuan Vo-Dinh Duke UniversityMatthew Wallenstein Colorado State UniversitySteve Wiley Pacific Northwest National Laboratory


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


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?



• 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

Representative Technologies

Outcome: Four Major Technology Needs for Understanding Biological Function

1. 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 Characterization Department of Energy • Office of Science • Biological and Environmental Research

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

Outcome: Four major technology needs for understanding biological function

1. 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

2. 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 heterogeneous backgrounds


Outcome: Four major technology needs for understanding biological function, continued

3. 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

4. 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


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.


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


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


Documents

DOE-OBER Workshop on New Frontiers in Characterizing Biological Systems