Major Trends in Biomedical Research

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Major Trends in Biomedical Research

  1. 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. 2. Francis S. Collins, M.D., Ph.D. New Pathways to Discovery: The Molecular Libraries and Imaging Roadmap Initiative
  3. 3. New Pathways to Discovery   Molecular Libraries and Imaging  Building Blocks, Biological Pathways and Networks  Structural Biology  Bioinformatics and Computational Biology  Nanomedicine
  4. 4. Four recent developments make small molecules/chemical genomics initiative possible Combinatorial Chemistry Robotic TechnologyHGP Availability of targets Availability of screening Availability of compounds Public sector screening and chemistry initiative Compound Availability
  5. 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. 6. 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
  7. 7.  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 Libraries Repository & Screening Centers
  8. 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. 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. 10. Structural Biology, Bioinformatics, Computational Biology and Nanomedicine Jeremy M. Berg, Ph.D.
  11. 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. 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. 13. 0 2 4 6 8 10 12 14 16 1960 1970 1980 1990 2000 numberofstructures 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
  14. 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. 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. 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. 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

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