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Major Trends in Biomedical Research

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  • 1.
    • 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 Working Group and Co-Chairs
  • 2. Francis S. Collins, M.D., Ph.D. New Pathways to Discovery: The Molecular Libraries and Imaging Roadmap Initiative
  • 3.
    • New Pathways to Discovery
    •  
    • Molecular Libraries and Imaging
    • Building Blocks, Biological Pathways and Networks
    • Structural Biology
    • Bioinformatics and Computational Biology
    • Nanomedicine
  • 4. Four recent developments make small molecules/chemical genomics initiative possible Combinatorial Chemistry Robotic Technology HGP Compound Availability Availability of targets Availability of screening Availability of compounds Public sector screening and chemistry initiative
  • 5. 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
  • 6. Collaborative Pipeline of a NIH Chemical Genomics Center Screen Probe picking, confirmation, secondary screens Peer review Investigator Customized Assay Probe List Limited MedChem Compound Repository Cheminformatics, PubChem (NCBI) Assay
  • 7.
    • Small Molecule Repository
      • Contract award in 2004
    • Screening Centers
      • Intramural center: operational in 2004
      • Extramural centers: Request for Information issued 11/21/03
        • 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
        • Contract award in 2005
    Molecular Libraries Repository & Screening Centers
  • 8. 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
  • 9. 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
  • 10. Structural Biology, Bioinformatics, Computational Biology and Nanomedicine Jeremy M. Berg, Ph.D.
  • 11. Structural Biology
    • Initiative: Centers for Innovation in Membrane Protein Production
    • Applications due March 11, 2004
    • $5M FY2004 Roadmap funding (~2 Centers, P50 Mechanism)
  • 12. 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
  • 13. 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
  • 14. 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
  • 15. Bioinformatics and Computational Biology
    • Initiative: National Centers for Biomedical Computing
    • Applications received January 23, 2004
    • $12M FY2004 Roadmap funding (~4 Centers, U54 Mechanism)
  • 16. 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
  • 17. 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