Connecting the Nation's Researchers, Patients and Communities: Next Steps

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Connecting the Nation's Researchers, Patients and
Communities Next Steps Biological and
Environmental Research Advisory Committee
Department of Energy September 1, 2009
Barbara Alving, M.D., M.A.C.P. Director National
Center for Research Resources www.ncrr.nih.gov
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National Center for Research Resources Translating
research from basic discovery to improved
patient care
animal model resources
community engagement
science education
Pre-clinical
Improved patient care
Community
technology informatics advances
research capacity training
Clinical
clinical research support
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NCRR Div Clinical Research Clinical and
Translational Science Awards (will include 60
academic health centers working as a consortium
and as a cooperative agreement with NIH)

• To ensure new discoveries lead to improved public
  health, clinical science must evolve to better
• Implement biomedical discoveries
• Develop, test, and bring new prevention
  strategies into medical practice more rapidly
• Catalyze change - lower barriers between
  disciplines
• Encourage creative and innovative approaches.

www.CTSAWeb.org
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Five CTSA Strategic Goals

• To enhance
• National Clinical Research Capability and
  Efficiency
• Training and Career Development of Clinical and
  Translational Investigators
• Consortium-Wide Collaborations
• Health of Our Communities and the Nation
• T1 Translational Research

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NCRR Division of Biomedical Technology Translating
discoveries into tools for biomedical research

• Biomedical Technology Research Centers (BTRC)
• Shared Instrumentation
• High-End Instrumentation
• Investigator-Initiated Research Grants (R01, R21)
• Biomedical Informatics Research Network (BIRN)
• Small Business Opportunities (SBIR/STTR)

Advances in technology open new areas of inquiry
Technology
Discovery
Biomedical discoveries create a need for new
technologies
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Shared and High-End Instrumentation Program
(S10) Overview

• Unique and critical NIH mechanisms
• Provide funding in cost-range from 100K to 2.0M
• SIG Program (funding range 100k to 500K)
• HEI Program (funding range 750k to 2.0M)
• Equipment which is too costly to obtain with
  regular NIH research grants
• Highly cost-effective mechanisms
• Instruments placed in core facilities
• Shared by an average of 8-10 grantees

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Biomedical Informatics Research Network (BIRN) A
shared biomedical IT infrastructure

• Collaboration between groups with different
  expertise and resources (technical, scientific,
  social and political)
• Shared infrastructure to support collaboration
  (designed to be extensible to other biomedical
  communities)
• Open access and dissemination of data and tools
  (i.e. Open Source)
• Bringing transparent GRID Computing to Biomedical
  Research

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BTRCs 52 Nationally Accessible Engines for
Translational Research
BTRCs
Individual Investigators NIH Programs CTSA Conso
rtium

• Enabling technologies
• Expertise
• Computing

Technology
Discovery
Each BTRC is accessible to NIH-supported
investigators and programs from across the nation.
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Biomedical Technology Research Centers

• 52 Unique Centers classified in 5 Broad Areas
• Scope from basic discovery to clinical research
• Scale from molecule to organism

• Technology for
• Structural Biology
• Synchrotron x-ray technologies
• Electron microscopy
• Magnetic resonance

• Technology for
• Systems Biology
• Mass spectrometry
• Proteomics
• Glycomics glycotechnology
• Flow cytometry

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Interagency Collaboration for Development of
Biomedical Technology

• NCRR interacts with DOE through our Biomedical
  Technology
• Research Centers (BTRC) program
• BTRC program
• BTRCs located at
• DOE National Laboratories
• Systems Biology BTRCs
• Structural Biology BTRCs
• 3 jointly supported with DOE/BER

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NCRR Leverages Resources at DOE National
Laboratories to support NIH research

• NCRR Division of Biomedical Technology
• Funds Biomedical Technology Research Centers
  (BTRC) to translate advances in physical sciences
  into tools for biomedical research
• DOE National Labs
• Facilitate RD that is expensive and complex
• Presents opportunities for NCRR to leverage
  unique expertise and infrastructure in the
  physical sciences
• Personnel
• Instrumentation development
• Instrumentation access

NCRR Enables 200M of NIH-funded research by
supporting nine BTRCs for 20M at seven National
labs through
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Systems Biology Biomedical Technology Research
Centers at National Laboratories
National Flow Cytometry Resource Los Alamos
National Laboratory National Resource for
Biomedical Accelerator Mass Spectrometry
Lawrence Livermore National Laboratory Proteomic
s Research Resource for Integrative Biology
Pacific Northwest National Laboratory

• Technology for
• Systems Biology
• Mass spectrometry
• Proteomics
• Glycomics glycotechnology
• Flow cytometry

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National Flow Cytometry Resourceat Los Alamos
National Laboratory (LANL)

• Development of new instrumentation and
  applications
• Access to unique LANL infrastructure
• Access to scientists with unique technical and
  mathematical capabilities
• Provides access to state-of-art flow cytometry
  instrumentation
• Provides training for the biomedical research
  community

New technology flow cytometry
based on sound waves
Training build a cytometer course
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A simple, low cost, compact data acquisition
system for compact, portable flow
cytometersNational Flow Cytometry Resource,
LANL

• Developed a data system for use in low cost
  and/or portable instruments, based on a
  commercial electronics board.
• NFCR makes these systems available to
  collaborators
• Relatively low cost (500)
• Technology licensed by Acoustic Cytometry
  Systems, which has since been acquired by
  Invitrogen

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National Resource for Biomedical Accelerator Mass
Spectrometry at Lawrence Livermore National
Laboratory (LLNL)

• Exquisitely sensitive technology for metabolic
  studies
• Allows safe microdosing with toxic or
  experimental molecules in humans
• 14C-AMS has allowed critical questions to be
  answered in human nutrition, metabolism,
  pharmacology, and comparative medicine.

1 Megavolt Biomedical AMS Instrument
10 Megavolt Instrument

• LLNL Center for Accelerator
• Mass Spectrometry (CAMS)
• is the foundation for the BioAMS BTRC
• Expertise
• Engineering
• Infrastructure

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Translating AMS Identification of
chemoresistance for personalized
chemotherapy National Resource for Biomedical
Accelerator Mass Spectrometry, LLNL

• Highly toxic chemotherapy is often ineffective
  (response rate for non-small cell lung cancer
  lt30, bladder cancer 50)
• Identify chemoresistance by measuring
  chemotherapy-induced cell damage
• Using ultrasensitive AMS, chemoresistance and the
  underlying mechanisms can be identified before
  patients receive toxic chemotherapy

Example 14C-labeled platinum derivatives, the
most commonly used chemotherapeutic drugs.
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Proteomics Research Resource Center for
Integrative Biology at Pacific Northwest
National Laboratory (PNNL)

• Ultra-sensitive high throughput proteomics
  technologies and supporting informatics
  capabilities
• Leverages a large base of DOE instrumentation,
  infra-structure, and EMSL DOE User Facility
  investments
• Growing number of clinical/translational
  proteomics applications (e.g. partner with UW
  and OHSU CTSAs)

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3-D mapping of proteins in mouse brain enabled
by voxelation and quantitative proteomics Proteom
ics Research Resource Center for Integrative
Biology, PNNL
Collaboration with Prof. Desmond Smith UCLA

• Spatial mapping of protein abundances in
  the mouse brain by voxelation integrated with
  high-throughput liquid chromatography-mass
  spectrometry. V.A. Petyuk, W.-J. Qian, M.H.
  Chin, H. Wang, E.A. Livesay, M.E. Monroe, J.N.
  Adkins, N. Jaitly, D.J. Anderson, D.G. Camp II,
  D.J. Smith, R.D. Smith. Genome Research 17,
  328-336 (2007).

• Analysis of one voxelated mouse brain at 1 mm
  resolution requires proteome analysis of 700
  tissue samples
• Quantitation and spatial distributions obtained
  for gt1000 distinct proteins

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Collaboration with the Inflammation and Host
Response to Injury Glue Grant (NIGMS)Proteomics
analysis 100 trauma subjects, over 7 time
points (12 hour intervals) Monocyte and T-cell
Proteins
Proteomics analysis Proteomics Research
Resource Center for Integrative Biology, PNNL
Patient classification based on 24 proteins
observed in T-cells
Good outcome Bad outcome

• High throughput quantitative proteomics
• Longitudinal analysis of T-cell and monocyte
  samples from severe trauma patients
• Revealed 24 proteins predictive of bad outcomes
  (multiple organ failure)
• Superior to microarray transcriptomic studies for
  same samples
• Extending to larger patient population
• Pathway analysis to establish biological context
  

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Structural Biology Biomedical Technology Research
Centers at National Laboratories
BioCARS A Synchrotron Structural Biology
Resource U of Chicago, APS, Argonne National
Laboratory Biophysics Collaborative Access Team
Illinois Institute of Tech, APS, Argonne
National Laboratory Undulator Resource for
Structural Biology Cornell U, APS, Argonne
National Laboratory Macromolecular
Crystallography at the National Synchrotron Light
Source Brookhaven National Laboratory,
NSLS Synchrotron Radiation Structural Biology
Resource Stanford, SSRL, SLAC National
Accelerator Laboratory National Center for X-Ray
Tomography UCSF, Lawrence Berkeley National
Laboratory

• Technology for
• Structural Biology
• Synchrotron x-ray technologies
• Electron microscopy
• Magnetic resonance

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Synchrotron BTRCs Leverage DOE Facilities
Develop New TechnologiesProvide Access for
Structural and Cellular Biology
WA
ME
MT
IIT, APS
ND
VT
Tom Irving
NY
Cornell U., APS
MN
OR
NH
MA
UCSF, LBNL
Steve Ealick
WI
ID
Carolyn Larabell
SD
MI
CT
WY
RI
PA


IA
NJ
Brookhaven
Stanford Univ
NE
IN
NV
Keith Hodgson
Bob Sweet
DE
OH
IL
UT
MD
WV
CO
VA
CA
DC
KS
MO
KY
U. Chicago, APS
NC
TN
Keith Moffat
OK
AR
AZ
SC
NM
AL
MS
GA
LA
TX
FL

• Over 40 of all research done at synchrotrons is
  in the life sciences

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Stanford Synchrotron Radiation Laboratoryat SLAC
National Accelerator Laboratory

• Cooperatively funded by NCRR and DOE/BER
• Integrates 3 structural biology technology
  development areas to serve the needs of the
  biomedical and environmental science communities
• Macromolecular crystallography
• X-ray absorption spectroscopy
• Small angle x-ray scattering
• Services feature robotics and remote data
  collection

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DNA Transcription and Regulation

• Research area of R. Kornberg most of the
  synchrotron work was performed at SSRL and
  strongly enabled by the robotics
• Transcription is the process by which DNA is
  read and converted into a message that directs
  protein synthesis with extremely high fidelity
• Synchrotron-enabled studies have
• provided molecular-level insight
• into the function of this molecular
• machine
• This structural information now
• serves to guide the development
• of new antibiotics

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National Center for X-ray Tomographyat the
Lawrence Berkeley National Laboratory
Imaging Room
Soft X-rays (517 eV)
Malaria-infected RBC
Microscope

• New technology to obtain 3D views of
• whole, hydrated cells in their native state at
• better than 50 nm resolution
• Bridges the mesoscale resolution gap,
• The middle area between light (200 nm) and
• electron microscopy (3 Ångstroms)
• Can locate position of tagged molecules with
  respect to unstained cell structures

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Life Sciences Beamlines at NSLS-IIat Brookhaven
National Laboratory

• NCRR and BER jointly fund beamlines
  for Life Sciences (biomedical and
  biological) research at the existing
  National Synchrotron Light
  Source at Brookhaven National
  Laboratory
• NSLS-II will replace NSLS, becoming operational
  in 2015
• NIH will construct new beamlines for life
  sciences that will benefit both NIH and DOE/BER
  Researchers
• NCRR looks forward to continued cooperative
  funding of the life sciences programs at NSLS-II
  with DOE/BER

NSLS 1984-2012
NSLS-II, 2015-
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NCRR and DOE work cooperatively to support Life
Sciences Research

• DOE
• National Labs facilitate RD that is expensive
  and complex
• unique expertise and infrastructure in the
  physical sciences
• NCRR Division of Biomedical Technology
• translates advances in physical sciences into
  tools for biomedical research
• DOE / NCRR Interaction
• 9 BTRCs at 7 National Labs
• Collaborations with BER to advance unique
  technologies for
• biological and environmental research
• Enable 200M of NIH-funded research

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American Recovery and Reinvestment Act (ARRA)
Budget Components

Other HHS (AHRQ) to also transfer
ARRA appropriated 10 Billion (B) directly to NIH
8.2 B
1.0 B
0.5 B
0.3 B
0.4 B
Extramural Scientific Research (All ICs, OD)
Extramural Construction (NCRR)
Intramural Repair Improvement Constr. (BF)
SIG Other Cap Equip (NCRR)
Comparative Effectiveness Research (OD)
Financial Employment Reporting
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NCRR Funding through ARRA

• 1.0 Billion for construction, repair and
  renovation
• RFA for Extramural Research Facilities
  Improvement Program (C06)
• RFA for Core Facility Renovation, Repair and
  Improvement (G20)
• 300 Million for shared instrumentation and other
  capital research equipment
• RFA for Shared Instrumentation Grant (SIG)
• RFA for High End Instrumentation (HEI)
• 310 Million for scientific research
• Supplements to existing resource programs in NCRR