connecting the nation's researchers, patients and communities: next steps
DESCRIPTION
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. - PowerPoint PPT PresentationTRANSCRIPT
National Center forResearch Resources NATIONAL INSTITUTES OF HEALTH T r a n s l a t I n g r e s e a r c h f r o m b a s i c d i s c o v e r y t o i m p r o v e d p a t I e n t c a r e
Connecting the Nation's Researchers, Patients and Communities: Next Steps
Biological and Environmental Research Advisory Committee Department of EnergySeptember 1, 2009
Barbara Alving, M.D., M.A.C.P.Director
National Center for Research Resourceswww.ncrr.nih.gov
NCRR
ClinicalClinical
Community
National Center for Research ResourcesTranslating research from basic discovery to improved patient care
Improved patient
care
Pre-clinical
animal model resources
technology & informatics advances
clinical research support
research capacity
& training
community engagement
science education
NCRR
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 To ensure new discoveries lead to improved public health, clinical science improved public health, clinical science must evolve to better:must evolve to better:
Implement biomedical discoveriesDevelop, test, and bring new prevention strategies into medical practice more rapidlyCatalyze change - lower barriers between disciplinesEncourage creative and innovative approaches.
www.CTSAWeb.org
NCRR
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
NCRR
NCRR Division of Biomedical TechnologyTranslating 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)
Technology Discovery
Advances in technology open new areas of inquiry
Biomedical discoveries create a need for new technologies
NCRR
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
NCRR
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
Biomedical Informatics Research Network (BIRN)A shared biomedical IT infrastructure
NCRR
BTRCs: 52 Nationally Accessible Engines for Translational Research
IndividualInvestigators
NIH Programs
CTSAConsortium
IndividualInvestigators
NIH Programs
CTSAConsortium
Technology Discovery
• Enabling technologies
• Expertise
• Computing
Each BTRC is accessible to NIH-supported investigatorsand programs from across the nation.
BTRCs
NCRR
52 Unique Centers classified in 5 Broad Areas Scope: from basic discovery to clinical research Scale: from molecule to organism
Technology forStructural Biology
Synchrotron x-ray technologies
Electron microscopy
Magnetic resonance
Technology forSystems Biology
Mass spectrometry
Proteomics
Glycomics & glycotechnology
Flow cytometry
Optics & LaserTechnology
Microscopy
Fluorescence spectroscopy
In Vivo diagnosis
Imaging Technology
• MRI
• Image-guided therapy
• PET
• CAT
• Ultrasound
Informatics Resources
Genetics
Modeling of complex systems
Molecular dynamics
Visualization
Imaging informatics
Biomedical Technology Research Centers
NCRR
Interagency Collaboration for Development of Biomedical Technology
NCRR interacts with DOE through our Biomedical TechnologyResearch Centers (BTRC) program:
BTRC program
BTRCs located at
DOE National Laboratories
• Systems Biology BTRCs
• Structural Biology BTRCs3 jointly supported with DOE/BER
Technology forStructural Biology
Synchrotron x-ray technologies
Electron microscopy
Magnetic resonance
Technology forSystems Biology
Mass spectrometry
Proteomics
Glycomics & glycotechnology
Flow cytometry
NCRR
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 R&D 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
NCRR
Technology forSystems Biology
Mass spectrometry
Proteomics
Glycomics & glycotechnology
Flow cytometry
Systems Biology Biomedical Technology Research Centers at National Laboratories
National Flow Cytometry ResourceLos Alamos National Laboratory
National Resource for Biomedical Accelerator Mass Spectrometry Lawrence Livermore National Laboratory
Proteomics Research Resource for Integrative Biology Pacific Northwest National Laboratory
National Flow Cytometry ResourceLos Alamos National Laboratory
National Resource for Biomedical Accelerator Mass Spectrometry Lawrence Livermore National Laboratory
Proteomics Research Resource for Integrative Biology Pacific Northwest National Laboratory
NCRR
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
National Flow Cytometry Resourceat Los Alamos National Laboratory (LANL)
NCRR
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
NCRR
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.
LLNL Center for Accelerator
Mass Spectrometry (CAMS)
is the foundation for the BioAMS BTRC•Expertise•Engineering•Infrastructure
1 Megavolt Biomedical AMS Instrument
10 Megavolt Instrument
NCRR
Highly toxic chemotherapy is often ineffective (response rate for non-small cell lung cancer <30%, 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
Translating AMS: Identification of chemoresistance for personalized chemotherapyNational Resource for Biomedical Accelerator Mass Spectrometry, LLNL
Example: 14C-labeled platinum derivatives, the most commonly used chemotherapeutic drugs.
amol
14C/
mg
of D
NA
0
Time (h)0 5025
10
testicular cancer cells (sensitive to drug)
Breast and bladder cancer cells (resistant to drug)
Oxaliplatin-induced DNA adducts in cell lines
NCRR
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)
Next Generation Proteomics Platform: Prototype LC-IMS-MS
22
27
32
37
42
1400
100
m/z
41
21
26
31
36
1400
100
m/z
0 3 6 9 12
15Time (minutes)
Inte
nsit
y
24
29
34
39
44
1400
100
m/z
IMS Drift TimeIMS Drift Time
IMS Drift TimeIMS Drift Time
IMS Drift TimeIMS Drift Time
IMS Drift TimeIMS Drift Time
NCRR
“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).
3-D mapping of proteins in mouse brain enabled by voxelation and quantitative proteomicsProteomics Research Resource Center for Integrative Biology, PNNL
Analysis of one voxelated mouse brain at 1 mm resolution requires proteome analysis of ~700 tissue samples
Quantitation and spatial distributions obtained for >1000 distinct proteins
Collaboration with Prof. Desmond Smith; UCLACollaboration with Prof. Desmond Smith; UCLA
NCRR
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
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
Good outcome Bad outcome
NCRR
Technology forStructural Biology
Synchrotron x-ray technologies
Electron microscopy
Magnetic resonance
Structural Biology Biomedical Technology Research Centers at National Laboratories
BioCARS: A Synchrotron Structural Biology ResourceU of Chicago, APS, Argonne National Laboratory
Biophysics Collaborative Access Team Illinois Institute of Tech, APS, Argonne National Laboratory
Undulator Resource for Structural BiologyCornell U, APS, Argonne National Laboratory
Macromolecular Crystallography at the National Synchrotron Light Source Brookhaven National Laboratory, NSLS
Synchrotron Radiation Structural Biology ResourceStanford, SSRL, SLAC National Accelerator Laboratory
National Center for X-Ray TomographyUCSF, Lawrence Berkeley National Laboratory
BioCARS: A Synchrotron Structural Biology ResourceU of Chicago, APS, Argonne National Laboratory
Biophysics Collaborative Access Team Illinois Institute of Tech, APS, Argonne National Laboratory
Undulator Resource for Structural BiologyCornell U, APS, Argonne National Laboratory
Macromolecular Crystallography at the National Synchrotron Light Source Brookhaven National Laboratory, NSLS
Synchrotron Radiation Structural Biology ResourceStanford, SSRL, SLAC National Accelerator Laboratory
National Center for X-Ray TomographyUCSF, Lawrence Berkeley National Laboratory
NCRR
Synchrotron BTRCs Leverage DOE Facilities Develop New TechnologiesProvide Access for Structural and Cellular Biology
MT
WY
ID
WA
OR
NV
UTCA
AZ
ND
SD
NE
CO
NM
TX
OK
KS
AR
LA
MO
IA
MN
WI
IL
IN
KY
TN
MS AL GA
FL
SC
NC
VAWV
OH
MI
NY
PA
MDDE
NJ
CTRI
MA
ME
VTNH
DC
Brookhaven
U. Chicago, APS
IIT, APS
Stanford Univ
Cornell U., APS
UCSF, LBNL
Over 40% of all research done at synchrotrons is in the life sciences
Keith Hodgson
Steve Ealick
Bob Sweet
Keith Moffat
Carolyn Larabell
Tom Irving
NCRR
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
NCRR
• 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
DNA Transcription and Regulation
2006 Chemistry Nobel Prize - R.
Kornberg
NCRR
National Center for X-ray Tomographyat the Lawrence Berkeley National Laboratory
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
Imaging RoomSoft X-rays
(517 eV)
Microscope
ParasiteNucleusHemoglobinMaurer’s cleftsDigestive vac.
Malaria-infected RBC
Malaria-infected RBC
NCRR
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
Life Sciences Beamlines at NSLS-IIat Brookhaven National Laboratory
NSLS 1984-2012
NSLS-II, 2015-
NCRR
NCRR and DOE work cooperatively to support Life Sciences Research
DOE– National Labs facilitate R&D 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
NCRR
American Recovery and Reinvestment Act (ARRA) Budget Components
Financial & Employment Reporting
Extramural Scientific Research
(All ICs, OD)
ExtramuralConstruction
(NCRR)
Intramural Repair &
Improvement & Constr.
(B&F)
SIG & Other Cap
Equip (NCRR)
$8.2 B $1.0 B $0.5 B $0.3 B
ARRA appropriated $10 Billion (B) directly to NIHOther HHS (AHRQ) to also transfer
$0.4 B
Comparative Effectiveness
Research(OD)
NCRR
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