Life & Medical Sciences DivisionLife & Medical Sciences DivisionStatus ReportStatus Report

David ThomassenActing Division Director

Life & Medical Sciences DivisionLife & Medical Sciences Division

Who are we?Sharon Betson – Secretary Joanne Corcoran – Program

Assistant

Dean Cole – Artificial retina Dan Drell – GTL, JGI, ELSI

Patrick Glynn – BRCs Joe Graber – AAAS Fellow, GTL

Susan Gregurick – Computation, GTL, JGI Roland Hirsch – Structural Biology, GTL

John Houghton – GTL, BRCs Arthur Katz – GTL, Low Dose Radiation

Peter Kirchner – Human subjects, Imaging Noelle Metting – Low Dose Radiation

Prem Srivastava – Radiochemistry Michael Teresinski – Laboratory Safety

Marvin Stodolsky – GTL, Genomics, SBIR Sharlene Weatherwax – GTL, BRCs, JGI

Libby White – Human Subjects

Office of Science

U.S. Department of Energy

Life & Medical Sciences DivisionLife & Medical Sciences DivisionOffice of Science

U.S. Department of Energy

What do we do?

• Genomics:GTL (including ELSI)

• Joint Genome Institute

• Low Dose

• Structural Biology

• Radiopharmaceuticals, imaging, retina

• Protection of Human Subjects

Dates: June 8-11, 2008Location: Germantown, MDCOV chair: Dr. Peg Riley, BERAC

22 COV members from academic institutions and other federal agencies.

The COV is charged to assess the processes used to:–solicit, review, and recommend proposal funding actions –manage ongoing research programs–respond to the recommendations of the previous COV in 2005.

Specific program elements to be reviewed include:– Genomics:GTL (including the Bioenergy Research Centers)– Carbon Sequestration– ELSI– Low Dose Radiation Research– Radiochemistry and Instrumentation– Artificial Retina– Joint Genome Institute– Structural Biology

(Medical Sciences programs were merged with Life Sciences Research programs in 2006 and will be undergoing their first COV review.)

A report will be provided at the next BERAC meeting.

Office of Science

U.S. Department of Energy

Life & Medical Sciences – COV UpdateLife & Medical Sciences – COV Update

Life & Medical Sciences - SolicitationsLife & Medical Sciences - SolicitationsOffice of Science

U.S. Department of Energy

• Low Dose (with NASA) – fundamental mechanisms

• Low Dose - integrated program projects

• Plant feedstock genomics with USDA

• Radiochemistry & imaging instrumentation

• Genomics:GTL for biohydrogen

DOE Bioenergy Research Centers: DOE Bioenergy Research Centers: Multi-Institutional PartnershipsMulti-Institutional Partnerships

Office of Science

U.S. Department of Energy

BioEnergy Science Center (BESC)BioEnergy Science Center (BESC)

• Strong central strategic focus on overcoming “recalcitrance” (resistance of plant fiber, or lignocellulose, to breakdown into sugars) as major route to cost savings and cost-effective biofuels production

• Longer-term goal of “Consolidated Bioprocessing” (CBP) – one-microbe or microbial community approach going from plants to fuel

• Working directly on energy crops – switchgrass and poplar • Nearly completed development new high-throughput pipeline to screen

thousands of genetic variants of switchgrass and poplar for amenability to deconstruction

• Performed bioprospecting in Yellowstone National Park for cellulases that operate more efficiently at very high temperatures – using metagenomics to find new, more effective cellulases

• Pursuing synthetic biology to make Clostridium thermocellum (CBP microbe) more efficient at fermenting and to re-engineer the cellulosome

• Strongly committed to achieving cost-saving, commercializable breakthroughs in five years

• Will eventually have the opportunity to test discoveries in a demonstration biorefinery being constructed by the state of Tennessee 40 miles from BESC

Office of Science

U.S. Department of Energy

Joint BioEnergy Institute (JBEI)Joint BioEnergy Institute (JBEI)

• Strong basic science-oriented approach, looking for fundamental transformational, game-changing breakthroughs in basic science

• Focusing on model crops of Arabidopsis and rice (and on switchgrass) – with idea that basic science breakthroughs can be achieved more rapidly on model crops and then transferred to energy crops

• Innovative approach to lignin – rather that treat lignin as a wall to be broken through, change the monomer composition of lignin to make it more cleavable and its byproducts less toxic to microbes used in fuel synthesis

• Progress on pretreatment – success already using ionic liquids as an alternative pretreatment method—yields no toxic byproducts and de-crystallizes the cellulose – significantly accelerates enzymatic hydrolysis

• Especially creative on the microbial side – using synthetic biology, looking beyond ethanol to synthesis of butanol, isopentanol, hexadecane, geranyl decanoate (toward gasoline, diesel, jet fuel)

• All researchers will work together in a newly leased lab building near Berkeley – move to new quarters in Emeryville nearly completed

• Fostering strong connections to larger S.F. Bay Area Biotech Community, which is becoming hub of bioenergy technology and venture investment

Office of Science

U.S. Department of Energy

Great Lakes Bioenergy Research Center Great Lakes Bioenergy Research Center (GLBRC)(GLBRC)

• Reflecting agronomic orientation of the two universities, focusing on a wide range of plants, including both “model” plants and potential bioenergy crops – also in some ways the most diverse research agenda

• Alternative approach to plants – in addition to working to overcome “recalcitrance” of lignocellulose, GLBRC will be re-engineering plants to produce more starches and oils, which are more easily processed into fuels – oils for biodiesel

• Alternative approaches to fuels:– Exploring chemical catalytic as well as enzymatic/microbial

conversion – producing hydrocarbons – green gasoline, diesel, aviation fuel – new approach of “aqueous phase processing” yields hydrocarbons from sugars

– Developing microbial biorefineries that can use sunlight and plant biomass to generate hydrogen, electricity, or high-energy chemicals

• Includes major “thrust area” on sustainability of biofuels production, comprehensively studying the environmental and socioeconomic dimensions of moving to a biofuels economy (not requested in FOA, but widely praised by peer reviewers and important for moving toward President’s “20 in 10” goal) – of growing importance in new societal debate on biofuels – actively working to educate public, community

Office of Science

U.S. Department of Energy

ASCR-BER Joint EffortsASCR-BER Joint EffortsAccelerating Progress Toward GTL GoalsAccelerating Progress Toward GTL Goals

PAST: SciDAC and GTL Efforts:Current research within the SciDAC/GTL program includes new

molecular dynamics codes for very large biological systems such as Cellulases, network analysis for hydrogen metabolism, and programs, such as BACTER, aimed at bridging the computational/experimental microbiology gap.

PRESENT: Multiscale Modeling Efforts between GTL and ASCR:Proposals were solicited for joint activities to interface computational

and mathematical efforts with biological mission relevant research directions. Areas under consideration include large scale genotyping and simulations of microbial communities, large scale network analysis and coarse graining of dynamical processes.

FUTURE: GTL Systems Biology Knowledgebase Workshop:A workshop will outline the mechanism necessary to create a community

driven resource for the archival, curation and integration of data and information that is relevant to the organisms of interest and mission areas of DOE. Particular emphasis is given to creating a computational and collaborative infrastructure. (Reported by Susan Gregurick yesterday.)

Office of Science

U.S. Department of Energy

Life & Medical Sciences DivisionLife & Medical Sciences DivisionGTL Update ContinuedGTL Update Continued

Office of Science

U.S. Department of Energy

Addressing Deficiencies in Genomic Annotation

• More genomic sequences require more robust annotation

• Experimental confirmation of annotation lags far behind

• Investing in innovative experimental approaches

Understanding Lignocellulose Degradation

• Improving lignocellulose degradation key to using non food feedstocks

• Investments focus on understanding degradation through imaging

• Range of techniques with higher risk

complement and support BRC needs

LigninHemicelluloseCellulose

Life & Medical Sciences DivisionLife & Medical Sciences DivisionRecent Sequencing SuccessesRecent Sequencing Successes

Office of Science

U.S. Department of Energy

• Chlamydomonas reinhardtii – green alga, carbon processing machine

• Trichoderma reeseii – champion biomass degrading fungus

• Laccaria bicolor – symbiotic fungus of Poplar and others

• Soybean – of bioenergy interests to many

• Termite hind gut metagenome – enzymes for lignocellulose degradation

• New tool for metagenome data management & analysis (http://img/jgi/doe/gov/m)

ResearchReviews

(Risk Estimates)UNSCEAR

BEIR

RecommendationsNCRPICRP

NationalStandards

EPANRCDOE

Radiation Protection Standards: Radiation Protection Standards: Development SequenceDevelopment Sequence

Low Dose Radiation Biology

And standards may change.

New studies of low dose human cohorts

If the risk is judged to be lower …

Recommendations may be modified …

“better scientific understanding and consensus”

Low dose data only

RadiationEpidemiology

RERF JCCRER

Low dose epidemiology

High bkg areas Nuclear workers Radiation workers

Office of Science

U.S. Department of Energy

• Workshop planned to discuss epidemiology needs• Tentatively November 2008

• Research shows extrapolation from A-bomb survivors not optimal

• Update, extend available studies of human cohorts

• Modify study designs: ecological cohort

• Appropriate comparison populations

• Dose Ranges charts now translated into Spanish, Russian, Georgian, Chinese, and Latvian (PNNL

Interdict/RADACAD)

Office of Science

U.S. Department of Energy

Low Dose Radiation Research ProgramLow Dose Radiation Research Program

Structural BiologyStructural BiologyStatus of major projectsStatus of major projects

• NSLS protein crystallography program reviewed in 2003, renewed for five years; latest renewal reviewed jointly with NIH-NCRR in March, 2008

• SSRL structural molecular biology program reviewed in 2004; renewed for five years

• ALS programs all now part of a single Science Focus Area, but with distinct budgets and review plans; x-ray microscopy renewal application due to nih this month

• LANSCE protein crystallography station program renewed in 2005

• APS Structural Biology Center reviewed and renewed in 2006

• SANS station at Oak Ridge has completed a full year of operation; renewal review to take place in coming year

• Competitive renewal of PDB in progress with NSF and NIH

Office of Science

U.S. Department of Energy

Structural Biology – Pending IssuesStructural Biology – Pending Issues

• National Synchrotron Light Source to be replaced. How will life sciences access be developed and what new techniques will be enabled by the facility?

• How important are neutron techniques and how much should BER invest in

user stations for them? [This question from 2005 is still unanswered.]

• To what extent should the structural biology facility access program focus

on needs of the Genomics:GTL program? Several beamlines are being

used in GTL technology development and/or research, will more, or new

types, be needed?

• Are there areas for which a program solicitation would be desirable, perhaps

jointly with other agencies?

Office of Science

U.S. Department of Energy

• Other new national user facilities, such as the Linac Coherent Light Source (LCLS), and major facility upgrades. What is the potential impact on life sciences in general and on BER research programs?

Radiochemistry & Imaging - UpdateRadiochemistry & Imaging - UpdateOffice of Science

U.S. Department of Energy

• FY 2007 Program Funding ($6.05M): Supported radiotracer and advanced imaging instrumentation for medical research and technology development activities mainly at BNL, and some imaging instrumentation work at other DOE laboratories including LANL, LBNL, ORNL and T. J. Laboratory.

• FY 2008 Omnibus Bill: Congress provided additional $17.5M for nuclear medicine research. Solicitation issued. Formal applications encouraged from the initial pre-application phase and submitted in response to Funding Opportunity Announcement in the area of Radiochemistry and Instrumentation Research will be reviewed for scientific merit, and making grant awards in FY 2008.

track RNA movements

er

report gene activation

report metabolite levels

Artificial Retina Argus I UpdateArtificial Retina Argus I Update

■ 16 microelectrode implant■ Six blind patients implanted ■ No device failures■ Implant still operating after over

6 yr of daily use■ Demonstrated feasibility of

artificial retina prosthesis■ Patients can see large print

Office of Science

U.S. Department of Energy

Next Generation Argus II Next Generation Argus II UpdateUpdate

• Argus II– 60 microelectrode device

– RF power and data transmission

– Smaller implant• Reduced surgical time (2.5 hours)

– Advanced image processing• Real time

• Portable

– Reliable• Designed to last a lifetime

• Extensive in vivo and in vitro testing

Office of Science

U.S. Department of Energy

Argus II Clinical TrialsArgus II Clinical Trials

• Worldwide Testing– United States

• FDA approval for 3 yr feasibility IDE

• 10 patients implanted at multi-centers in US

– No damaging effect after 8 months of daily use

– Europe• 3 patients implanted in Geneva and

the UK

– Latin America• 2 patients implanted

www.clinicaltrials.gov/ct/show/NCT00407602www.clinicaltrials.gov/ct/show/NCT00407602

Office of Science

U.S. Department of Energy

Protection of Human Research SubjectsProtection of Human Research SubjectsOffice of Science

U.S. Department of Energy

• New Program Manager – Libby White

• 2007 site visits – LBNL, LLNL, Fermilab

• Coordination with NNSA

• DOE Human Subject Working Group

• DOE resources – resource book, newsletter, resource group

• DOE human subjects database

• Coordination with Health & Human Services Office for Human Research Protections – 2008 site reviews planned for Sandia (+ 2 more)

• Lab accreditations to date (BER will support initial and ongoing costs) – PNNL (2008), BNL (in process)