Download Major Trends in Biomedical Research

NEW PATHWAYS TO DISCOVERY
Working Group and Co-Chairs
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Molecular Library and Imaging
Francis Collins, NHGRI
Tom Insel, NIMH
Rod Pettigrew, NIBIB
Building Blocks and Pathways
Francis Collins,NHGRI
Richard Hodes, NIA
T-K Li, NIAAA
Allen Spiegel, NIDDK
Structural Biology
Jeremy Berg, NIGMS
Paul Sieving, NEI
Bioinformatics and Computational Biology
Jeremy Berg, NIGMS
Don Lindberg, NLM
Nanomedicine
Jeffery Schloss, NHGRI
Paul Sieving, NEI
New Pathways to Discovery:
The Molecular Libraries and
Imaging Roadmap Initiative
Francis S. Collins, M.D., Ph.D.
New Pathways to Discovery
 Molecular Libraries and Imaging
 Building Blocks, Biological Pathways and Networks
 Structural Biology
 Bioinformatics and Computational Biology
 Nanomedicine
Four recent developments make
small molecules/chemical genomics
initiative possible
HGP
Combinatorial
Chemistry
Availability of
targets
Compound
Availability
Availability of
compounds
Public sector screening
and chemistry initiative
Robotic
Technology
Availability of
screening
Molecular Libraries:
Putting Chemistry to Work for
Medicine
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Six national screening centers for small
molecules
Public database for “chemical genomics”
Technology advances in combinatorial
chemistry, robotics, virtual screening
Collaborative Pipeline of a
NIH Chemical Genomics Center
Peer
review
Assay
Customized
Assay
Compound
Repository
Investigator
Screen
Limited
MedChem
Cheminformatics,
PubChem
(NCBI)
Probe List
Probe picking, confirmation,
secondary screens
Molecular Libraries
Repository & Screening Centers
 Small Molecule Repository
 Contract award in 2004
 Screening Centers
 Intramural center: operational in 2004
 Extramural centers: Request for Information issued
11/21/03
o received responses from universities and a few small
biotechnology companies
 RFA release in Mar., receipt date summer, awards in spring
2005
 Coordinating center for repository and screening centers
o Contract award in 2005
Molecular Imaging Roadmap
Components
 Development of high resolution probes for cellular
imaging
 RFA issued in 2004
 http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-04001.html
 Development of an imaging probe database
 In process, with links to PubChem
 Core synthesis facility to produce imaging probes
 Efforts to establish an intramural facility are underway
Potential Outcomes of Molecular
Libraries & Imaging Probes Activities
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Development of research tools (molecular probes
and novel assays) to facilitate studies of biology
and pathophysiology
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Advances in biological research leading to the
identification and validation of novel biological
targets for therapeutics development
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Discovery of biological markers to monitor disease
progression and to predict treatment response
Structural Biology, Bioinformatics,
Computational Biology
and Nanomedicine
Jeremy M. Berg, Ph.D.
Structural Biology
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Initiative: Centers for Innovation in
Membrane Protein Production
Applications due March 11, 2004
$5M FY2004 Roadmap funding (~2 Centers,
P50 Mechanism)
Centers for Innovation in Membrane
Protein Production
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Many physiologically and pharmaceutically
important proteins are membrane proteins
Few membrane proteins structures known
All eukaryotic membrane protein structures
determined to date have been from proteins derived
from naturally rich sources
Detergents and other agents required for
solubilization and crystallization
Development of methods for the production of
structurally and functionally intact membrane
proteins for subsequent structural studies
16
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14
B.W. Matthews Ann. Rev. Phys.
Chem. 27, 493 (1976)
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number of structures
12
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 water-soluble proteins
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10
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8
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6
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 membrane proteins
http://www.mpibp-frankfurt.pg.de/
michel/public/memprotstruct.html
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4
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2
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0
1960
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 
1970

1980
year
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 
1990
2000
progress in membrane protein structure determinations
parallels that of water-soluble proteins with a ~25 year offset
Courtesy of Doug Rees, Caltech
Structural Biology Roadmap Plans
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Wide range of structural biology programs
throughout NIH (intramural and extramural)
Synchrotron sources (NCRR, NCI, NIGMS)
and NMR instrumentation (NCRR, NIGMS)
supported
Protein Structure Initiative-Network of
Centers devoted to structural genomics
Roadmap initiatives will be used to provide
integration of these programs
Bioinformatics and Computational
Biology
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Initiative: National Centers for Biomedical
Computing
Applications received January 23, 2004
$12M FY2004 Roadmap funding (~4
Centers, U54 Mechanism)
National Centers for Biomedical
Computing
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Partnerships of:
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Computer scientists
Biomedical computational scientists
Experimental and clinical biomedical and behavioral
researchers
Focused on software rather than hardware
Each National Center to have Driving Biological
Projects
Open source requirement
Programs in preparation for partnerships between
individual investigators and National Centers
Nanomedicine Roadmap Initiative
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Nanomedicine describes the interface of biology and
nanotechnology to understand and treat disease.
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Nanomedicine is a departure from the majority of
nanotechnology research in that it integrates biomolecular
processes toward developing therapies.
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Will need to develop new tools and a nanomedicine lexicon
for shared use by engineers and biologists.
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Next Steps: Concept Development Awards in ’04;
solicitation for Nanomedicine Development Centers in ‘05
2/2004