Download - Major Trends in Biomedical Research
Molecular Library and Imaging Francis Collins, NHGRI Tom Insel, NIMH Rod Pettigrew, NIBIB
Building Blocks and PathwaysFrancis Collins,NHGRI Richard Hodes, NIAT-K Li, NIAAA Allen Spiegel, NIDDK
Structural Biology Jeremy Berg, NIGMS Paul Sieving, NEI
Bioinformatics and Computational BiologyJeremy Berg, NIGMS Don Lindberg, NLM
Nanomedicine Jeffery Schloss, NHGRI Paul Sieving, NEI
NEW PATHWAYS TO DISCOVERYWorking Group and Co-Chairs
Francis S. Collins, M.D., Ph.D.
New Pathways to Discovery:The Molecular Libraries and Imaging Roadmap Initiative
New Pathways to Discovery
Molecular Libraries and Imaging
Building Blocks, Biological Pathways and Networks
Structural Biology
Bioinformatics and Computational Biology
Nanomedicine
Four recent developments makesmall molecules/chemical genomics
initiative possible
Combinatorial Chemistry
Robotic TechnologyHGP
Availability of targets
Availability of screening
Availability of compounds
Public sector screening and chemistry initiative
CompoundAvailability
Molecular Libraries:Putting Chemistry to Work for
Medicine 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
Investigator
Customized Assay
Screen
Probe picking, confirmation, secondary
screens
Probe List
Limited MedChem
Compound Repository
Cheminformatics, PubChem
(NCBI)
Assay
Peer review
Small Molecule Repository Contract award in 2004
Screening Centers Intramural center: operational in 2004 Extramural centers: Request for Information issued
11/21/03o 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 Libraries Repository & Screening Centers
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-04-
001.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
Development of research tools (molecular probes and novel assays) to facilitate studies of biology and pathophysiology
Advances in biological research leading to the identification and validation of novel biological targets for therapeutics development
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
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
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
0
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1960 1970 1980 1990 2000
nu
mb
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of s
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ctu
res
year
water-soluble proteins
membrane proteins
progress in membrane protein structure determinations parallels that of water-soluble proteins with a ~25 year offset
B.W. Matthews Ann. Rev. Phys. Chem. 27, 493 (1976)
http://www.mpibp-frankfurt.pg.de/michel/public/memprotstruct.html
Courtesy of Doug Rees, Caltech
Structural Biology Roadmap Plans
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
Initiative: National Centers for Biomedical Computing
Applications received January 23, 2004 $12M FY2004 Roadmap funding (~4
Centers, U54 Mechanism)
National Centers for Biomedical Computing
Partnerships of: 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
Nanomedicine describes the interface of biology and nanotechnology to understand and treat disease.
Nanomedicine is a departure from the majority of nanotechnology research in that it integrates biomolecular processes toward developing therapies.
Will need to develop new tools and a nanomedicine lexicon for shared use by engineers and biologists.
Next Steps: Concept Development Awards in ’04; solicitation for Nanomedicine Development Centers in ‘05
2/2004