Connecting the Nation
This presentation is the property of its rightful owner.
Sponsored Links
1 / 28

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


  • 62 Views
  • Uploaded on
  • Presentation posted in: General

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.

Download Presentation

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

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Connecting the nation s researchers patients and communities next steps

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


Connecting the nation s researchers patients and communities next steps

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


Connecting the nation s researchers patients and communities next steps

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


Connecting the nation s researchers patients and communities next steps

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


Connecting the nation s researchers patients and communities next steps

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


Shared and high end instrumentation program s10 overview

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


Connecting the nation s researchers patients and communities next steps

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


Btrcs 52 nationally accessible engines for translational research

BTRCs: 52 Nationally Accessible Engines for Translational Research

BTRCs

Individual

Investigators

NIH Programs

CTSA

Consortium

  • Enabling technologies

  • Expertise

  • Computing

Technology

Discovery

Each BTRC is accessible to NIH-supported investigators

and programs from across the nation.


Biomedical technology research centers

Biomedical Technology Research Centers

  • Imaging

  • Technology

  • MRI

  • Image-guided therapy

  • PET

  • CAT

  • Ultrasound

Informatics

Resources

  • Genetics

  • Modeling of complex systems

  • Molecular dynamics

  • Visualization

  • Imaging informatics

Optics & Laser

Technology

  • Microscopy

  • Fluorescence spectroscopy

  • In Vivo diagnosis

  • 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


Interagency collaboration for development of biomedical technology

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

Technology for

Structural Biology

  • Synchrotron x-ray technologies

  • Electron microscopy

  • Magnetic resonance

Technology for

Systems Biology

  • Mass spectrometry

  • Proteomics

  • Glycomics & glycotechnology

  • Flow cytometry


Ncrr leverages resources at doe national laboratories to support nih research

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


Systems biology biomedical technology research centers at national laboratories

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

Proteomics Research Resource for Integrative Biology

Pacific Northwest National Laboratory

Technology for

Systems Biology

  • Mass spectrometry

  • Proteomics

  • Glycomics & glycotechnology

  • Flow cytometry


Connecting the nation s researchers patients and communities next steps

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


Connecting the nation s researchers patients and communities next steps

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


Connecting the nation s researchers patients and communities next steps

National Resource for Biomedical Accelerator Mass Spectrometryat 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


Connecting the nation s researchers patients and communities next steps

10

testicular cancer cells (sensitive to drug)

amol 14C/mg of DNA

Breast and bladder cancer cells (resistant to drug)

0

50

0

25

Time (h)

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 <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

Oxaliplatin-induced DNA adducts in cell lines

Example: 14C-labeled platinum derivatives, the most commonly used chemotherapeutic drugs.


Connecting the nation s researchers patients and communities next steps

1400

1400

m/z

m/z

100

100

41

21

26

31

36

22

27

32

37

42

1400

m/z

IMS Drift Time

IMS Drift Time

100

24

29

34

39

44

Intensity

IMS Drift Time

IMS Drift Time

0

3

6

9

12

15

Time (minutes)

Proteomics Research Resource Center

for Integrative Biology

at Pacific Northwest National Laboratory (PNNL)

Next Generation Proteomics Platform: Prototype LC-IMS-MS

  • 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)


Connecting the nation s researchers patients and communities next steps

“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 proteomics

Proteomics Research Resource Center for Integrative Biology, PNNL

Collaboration with Prof. Desmond Smith; UCLA

  • 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


Connecting the nation s researchers patients and communities next steps

Proteomics analysis

Proteomics Research Resource Center for Integrative Biology, PNNL

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

  • 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

Patient classification based on 24 proteins observed in T-cells

Good outcome Bad outcome


Structural biology biomedical technology research centers at national laboratories

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


Connecting the nation s researchers patients and communities next steps

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

Brookhaven

NJ

Stanford Univ

NE

IN

NV

Keith Hodgson

Bob Sweet

DE

OH

IL

MD

UT

WV

CO

VA

CA

DC

KS

MO

KY

U. Chicago, APS

NC

TN

Keith Moffat

OK

AR

SC

AZ

NM

AL

MS

GA

LA

TX

FL

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


Stanford synchrotron radiation laboratory at slac national accelerator laboratory

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


Connecting the nation s researchers patients and communities next steps

2006 Chemistry Nobel Prize - R. Kornberg

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


Connecting the nation s researchers patients and communities next steps

Parasite

Nucleus

Hemoglobin

Maurer’s clefts

Digestive vac.

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


Life sciences beamlines at nsls ii at brookhaven national laboratory

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-


Ncrr and doe work cooperatively to support life sciences research

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


American recovery and reinvestment act arra budget components

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.

(B&F)

SIG &

Other Cap

Equip

(NCRR)

Comparative

Effectiveness

Research

(OD)

Financial & Employment Reporting


Ncrr funding through arra

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


  • Login