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Title: Life

Life Medical Sciences DivisionStatus Report
  • David Thomassen
  • Acting Division Director

Life Medical Sciences Division
  • Who are we?
  • Sharon Betson Secretary Joanne Corcoran
    Program Assistant
  • Dean Cole Artificial retina Dan Drell GTL,
  • Patrick Glynn BRCs Joe Graber AAAS Fellow,
  • 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

Life Medical Sciences Division
  • What do we do?
  • GenomicsGTL (including ELSI)
  • Joint Genome Institute
  • Low Dose
  • Structural Biology
  • Radiopharmaceuticals, imaging, retina
  • Protection of Human Subjects

Life Medical Sciences COV Update
  • Dates June 8-11, 2008
  • Location Germantown, MD
  • COV chair Dr. Peg Riley, BERAC
  • 22 COV members from academic institutions and
    other federal agencies.
  • The COV is charged to assess the processes used
  • solicit, review, and recommend proposal funding
  • manage ongoing research programs
  • respond to the recommendations of the previous
    COV in 2005.
  • Specific program elements to be reviewed include
  • GenomicsGTL (including the Bioenergy Research
  • Carbon Sequestration
  • ELSI
  • Low Dose Radiation Research
  • Radiochemistry and Instrumentation
  • Artificial Retina
  • Joint Genome Institute

Life Medical Sciences - Solicitations
  • Low Dose (with NASA) fundamental mechanisms
  • Low Dose - integrated program projects
  • Plant feedstock genomics with USDA
  • Radiochemistry imaging instrumentation
  • GenomicsGTL for biohydrogen

DOE Bioenergy Research Centers
Multi-Institutional Partnerships
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
  • 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

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
    methodyields 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
  • 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

Great Lakes Bioenergy Research Center (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
  • 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 Presidents 20 in
    10 goal) of growing importance in new societal
    debate on biofuels actively working to educate
    public, community

ASCR-BER Joint EffortsAccelerating 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
Life Medical Sciences DivisionGTL Update
  • Addressing Deficiencies in Genomic Annotation
  • More genomic sequences require more robust
  • Experimental confirmation of annotation lags far
  • 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

Life Medical Sciences DivisionRecent
Sequencing Successes
  • Chlamydomonas reinhardtii green alga, carbon
    processing machine
  • Trichoderma reeseii champion biomass degrading
  • Laccaria bicolor symbiotic fungus of Poplar and
  • 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)

Radiation Protection Standards Development
National Standards EPA NRC DOE
Recommendations may be modified
If the risk is judged to be lower
Recommendations NCRP ICRP
New studies of low dose human cohorts
Research Reviews (Risk Estimates) UNSCEAR BEIR
And standards may change.
Radiation Epidemiology RERF JCCRER Low dose
epidemiology High bkg areas Nuclear
workers Radiation workers
Low Dose Radiation Biology
better scientific understanding and consensus
Low Dose Radiation Research Program
  • 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

(No Transcript)
Structural BiologyStatus 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

Structural 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
  • 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
    GenomicsGTL 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
  • 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 - Update
  • 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

Artificial Retina Argus I Update
  • 16 microelectrode implant
  • Six blind patients implanted
  • No device failures
  • Implant still operating after over 6 yr of daily
  • Demonstrated feasibility of artificial retina
  • Patients can see large print

Next Generation Argus II Update
  • 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

Argus 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
Protection of Human Research Subjects
  • 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