Advisory Council Minutes, January 13-14, 2005

The National Advisory General Medical Sciences (NAGMS) Council was convened in closed session for its one hundred twenty-seventh meeting at 8:30 a.m. on Thursday, January 13, 2005.

Dr. Jeremy Berg, director of the National Institute of General Medical Sciences (NIGMS), presided as chair of the meeting. The meeting was open to the public on January 13 from 10:40 a.m. to 4:20 p.m. and was followed by the closed session from 4:20 p.m. until adjournment for consideration of grant applications.

Council Members Present:

Francine D. Berman, Ph.D.
Shelagh M. Ferguson-Miller, Ph.D.
Stanley Fields, Ph.D.
Kathleen M. Giacomini, Ph.D.
John C. Goodman, Ph.D.
Eric N. Jacobsen, Ph.D.
Corey Largman, Ph.D.
Jeffrey Mason, Ph.D.
Brian W. Matthews, Ph.D., D.Sc.
Richard I. Morimoto, Ph.D.
Gregory R. Reyes, M.D., Ph.D.
Theodora E. Joan Robinson, Ph.D.
Lisa Staiano-Coico, Ph.D.
Yu-li Wang, Ph.D.
Virginia A. Zakian, Ph.D.

Members Absent:

Laura Weiss Roberts, M.D.

Special Consultants Present:

Christopher M. Dobson, M.A., Ph.D., F.R.S.
Department of Chemistry
University of Cambridge
United Kingdom

George C. Hill, Ph.D. (present by telephone)
Associate Dean for Diversity in Medical Education
Department of Microbiology and Immunology
Vanderbilt University School of Medicine
Nashville, TN

Eaton E. Lattman, Ph.D.
Department of Biophysics
Johns Hopkins University
School of Arts and Sciences
Baltimore, MD

Alan F. Horwitz, Ph.D.
Department of Cell Biology
University of Virginia
Charlottesville, VA

James C. Paulson, Ph.D.
Department of Molecular Biology
Scripps Research Institute
La Jolla, CA

Ronald G. Tompkins, M.D., ScD.
Chief of Burn Service
Massachusetts General Hospital
Boston, MA

Council roster (available from NIGMS).

Members of the Public Present:

Mr. Robert Atcher, Los Alamos National Laboratory
Mr. James Bernstein, American Society for Pharmacology and Experimental Therapeutics
Ms. Heidi Ecker, American Psychological Society
Ms. Wendy Eichorst, Association of Independent Research Institutes
Mr. Eugene Isaac, Constella Group, Inc.
Ms. Pat Kobor, American Psychological Association
Ms. Eileen Resnick, Society for Women's Health Research
Ms. Barbara Wanchisen, Federation of Behavioral, Psychological, and Cognitive Sciences

Federal Employees Present:

Dr. Eve Barak, National Science Foundation
Dr. Christopher Greer, National Science Foundation
Dr. Helen Hansma, National Science Foundation

NIGMS employees and other NIH employees:

Please see the sign-in sheet (available from NIGMS).


I. Call to Order and Opening Remarks

II. Consideration of Minutes

The minutes of the September 9-10, 2004 meeting were approved as submitted.

III. Future Meeting Dates

The following dates for future Council meetings were confirmed:

May 19-20, 2005
September 22-23, 2005
January 26-27, 2006
May 18-19, 2006

IV. Council Operating Procedures

As is required each year, the Council was asked to approve its operating procedures. There are no substantial changes from previous years.

VI. Report from the Director, NIGMS

Dr. Berg introduced new Council members: Dr. Francine Berman, director of the San Diego Supercomputer Center; Dr. Kathleen Giacomini, chair of the department of biopharmaceutical sciences at University of California, San Francisco School of Pharmacy; Dr. John Goodman, founder and president of the National Center for Policy Analysis in Dallas, Texas; Dr. Brian Matthews, professor of physics and Howard Hughes Medical Institute Investigator at the University of Oregon, Eugene; Dr. Lisa Staiano-Coico, dean of the college of human ecology at Cornell University in Ithaca, NY; and new ex officio member from the Department of Defense, Dr. Jeffrey Mason, chair of the department of biophysics at the Armed Forces Institute of Pathology in Rockville, MD.

Dr. Berg announced staff appointments at NIH: Dr. David Schwartz was named director of the National Institute of Environmental Health Sciences to begin in April 2005, and Dr. David Abrams, director of the NIH Office of Behavioral and Social Sciences Research. He noted that HHS Secretary Tommy Thompson announced his resignation in December and that President Bush has named Michael Leavitt, currently administrator of the Environmental Protection Agency, to be the new HHS secretary.

Dr. Berg noted that two NIGMS grantees, Dr. Irwin Rose and Dr. Avram Hersko, had been named as two the three recipients of this year's Nobel Prize in chemistry for their discovery of ubiquitin-mediated protein degradation. He noted that two drugs, Velcade, developed based on the work of Rose and Hersko as well as NIGMS grantee Alfred Goldberg, and Prialt, developed based on the work of NIGMS grantee and former NAGMS Council member "Toto" Olivera, had been approved by the FDA and were now in use.

Dr. Berg commented on three major activities across NIH: the implementation of the Division of Extramural Activities Support (DEAS), the report of the working group of the Advisory Committee to the Director of NIH on Basic Behavior and Social Science Research, and the discussion of the new NIH policy on public access to scientific publications. He concluded by noting that the President had recently signed an Omnibus spending bill that included in the NIGMS budget with a 2.0% increase over the budget for FY 2004.

VII. Update on the NIGMS Budget and the NIH Roadmap

Dr. Berg presented an update on matters related to the FY 2004 NIGMS $1.9 billion budget. The largest portion of the Institute budget funds non-competing research grants, and the smallest portion (less than 0.7 percent) funds NIH Roadmap activities. Dr. Berg discussed recent budget trends and the driving forces that help determine funding success rates. He also described several management tools that Institute staff use to guide funding decisions, including special consideration for new investigators and those with little or no grant support, and the formal procedure for making decisions on awards to grantees with more than $750,000 of annual total direct support. Dr. Berg also presented an overview and update of NIH Roadmap plans and activities, noting that, by design, Roadmap funds will never exceed 1 percent of total agency expenditures.

VIII. Annual Update on the Protein Structure Initiative

Planning for the NIGMS-sponsored Protein Structure Initiative (PSI) project began in 1998, with NIGMS staff involvement that included several technical workshops and extensive consultations with the NAGMSC and other advisors. PSI Director Dr. John Norvell and three members of the PSI Advisory Committee (PSIAC) presented an annual progress report to the Council. Dr. Norvell summarized the plans and goals of the initial, 5-year PSI program, which funded research grants, pilot research centers, technical workshops, and several databases. The Institute has relied heavily on the PSIAC, a working group of the Council, to help manage the pilot centers and to plan the PSI's second, production phase, slated to begin in July 2005. Three members of the PSIAC group made individual presentations. Dr. Brian Matthews of the University of Oregon, chair of the PSIAC, described progress that the pilot centers have made in constructing structural genomics pipelines and in solving unique protein structures. Dr. Eaton Lattman of the Johns Hopkins University reported on new technologies and methods developed by the PSI pilot centers. Dr. Chris Dobson of the University of Cambridge discussed overall PSI progress, international structural genomics projects, and the impact of this new field on scientific research worldwide. More information about the PSI.

IX. Glue Grant Progress Report: Consortium for Functional Glycomics

Dr. James C. Paulson reviewed progress from the Consortium for Functional Glycomics (CFG) glue grant, aimed at defining the paradigms by which glycan-binding proteins (GBPs) and their ligands mediate cellular communication. Dr. Paulson described how functional glycomics represents a directed approach to elucidating functions of glycans and glycoconjugates by focusing on glycan structure, biosynthesis, and the binding specificity of the GBPs that recognize them as ligands. To facilitate progress in these areas, the CFG has created several unique resources available to the scientific community, including (i) a high-throughput glycan array to screen lectin binding against a comprehensive library of synthetic and naturally-occurring glycan structures; (ii) a custom, highly annotated "Glyco-gene" microarray chip; (iii) MALDI-TOF/MS profiling of N- and O-linked glycans to catalogue glycan structures comprising the human and murine glycomes; and (iv) a relational database and interfaces for acquiring CFG Core data and integrating/retrieving data stored in the relational database. Currently, the GBP database (containing approximately 150 murine and human GBPs), the Glycan database (containing nearly 7,500 entries), and the Glycosylation Pathways database are all able to integrate CFG data with information from public databases. Dr. Paulson presented examples of data produced by the CFG, and he demonstrated the public accessibility of CFG data stored in the relational database. More information about the CFG.

X. Glue Grant Progress Report: Inflammation and the Host Response to Injury

Dr. Ronald G. Tompkins summarized progress of the Inflammation and the Host Response to Injury glue grant, which includes genome-wide expression profiling in mice and humans. Dr. Tompkins noted that key goals at the end of Year 5 include identifying the genomic expression, proteomic, and phenotypic signatures that are observed temporally after a major injury with a successful outcome, as well as those markers that might predict an adverse outcome in patients with major injury. Dr. Tompkins cited several products already developed or under development. These include: analytical protocols for sample handling and processing across multiple performance sites; clinical treatment protocols; the Trauma-Related Database (TRDB); and several analytical tools, including a time-series analysis algorithm, a microfluidics blood collection platform, and a human proteomics database. Since the program enrolls trauma and burn patients and performs preliminary analyses, there is an ongoing effort to improve communications and interactions among the analysts, clinicians, and biologists in order to make "biological sense" of the vast data collected. Dr. Tompkins stated that using a team science approach, the program is well on its way to refining a TRDB prototype that will provide "intelligent" downloads of the demographics, clinical, genomics, proteomics, and other data for user-friendly data queries. Web-based access to the human and murine experimental data and protocols is available through the Consortium Membership Program. More information about the Inflammation and the Host Response to Injury program (link no longer available).

XI. Glue Grant Progress Report: Cell Migration Consortium

Dr. Rick Horwitz provided a progress report on the Cell Migration Consortium (CMC) glue grant project, which aims to overcome existing barriers in cell migration science by catalyzing the development of new technologies, reagents, data, and information. The CMC has established a collection of interdisciplinary Initiatives, or working groups, that include investigators from biological and non-biological disciplines (chemistry, bioengineering, physics, mathematics, and structural biology). Ongoing activities within the CMC Initiatives include determining the structure of complex macromolecular assemblies, developing novel reagents to detect spatially and temporally resolved signals, producing transgenic and conditional knockout mice, developing mathematical models of migration-related phenomena, identifying new migration-related molecules, developing technologies to determine post-translational modifications and interactions among migration molecules, developing new biomaterials for studying signal transduction, and developing new imaging and photomanipulation technologies. In the past year, CMC researchers have developed methods for the global determination of utilized phosphorylation sites on proteins, determined the high-resolution structures of several adhesion-related complexes, formulated mathematical models for lamellipodial and cytoskeletal dynamics and for complex signaling networks, developed correlation methods for determining concentrations and interactions of proteins in living cells at high temporal and spatial resolution, and identified several novel migration molecules by high-throughput screens. The group has also generated useful resources such as photoactivatable phosphopeptides and a novel class of reagents to detect activated signaling complexes. New efforts that have been initiated include RNAi screens, development of a PhosphoArray signaling chip, and development of instrumentation and software for high-throughput FRET analyses on individual cells growing in multiple-well formats. The CMC website has been redesigned to include Initiative activity tables that link (where appropriate) to data and publications, list collections of existing migration-related resources, and post clear statements about collaborations and interactions with the broader community. The goal for the coming year will be to integrate these resources into the CMC's emerging Cell Migration Knowledge base. More information about CMC activities and progress (link no longer available).

XII. Request to Extend Funding of P20 Exploratory Centers for Human Embryonic Stem Cell Research

In September 2003, three P20 Exploratory Centers were funded for 3 years in response to RFA GM-03-003. The solicitation indicated that NIGMS anticipated issuing a subsequent announcement for larger scale P50 centers, to be funded in FY 2006, for which the P20 grantees would be eligible to apply. The intent was to expand human embryonic stem cell (HESC) research and to give the existing P20 centers an opportunity to continue their activities without a gap in funding. However, given the current uncertainties of the HESC field and the early stage of research at the P20 Exploratory Centers, NIGMS staff believes that it is premature to decide which mechanism would best support continued HESC research and to expect a strong field of applicants. Therefore, NIGMS staff recommend waiting an additional year before deciding on the next initiative. In the meantime, NIGMS staff recommend extending the funding period of current P20 Exploratory Centers for an additional year. Dr. Marion Zatz requested, and received, Council approval to extend the HESC P20 Exploratory Centers funding for 1 year.


XIII. Review of Applications

A summary of applications reviewed by Council is available from NIGMS.


The meeting adjourned at 4:20 p.m. on Thursday, January 13, 2005.


I hereby certify that to my knowledge the foregoing minutes are accurate and complete.

Jeremy M. Berg, Ph.D.
National Advisory General Medical Sciences Council

Ann A. Hagan, Ph.D
Executive Secretary
National Advisory General Medical Sciences Council