NIGMS Structural Genomics Project Planning Meeting

NIH, Bethesda, Maryland

Start Date: 11/24/1998 8:00 AM

End Date: 11/24/1998 4:30 PM

The National Institute of General Medical Sciences (NIGMS) held a small workshop at NIH on November 24, 1998 to seek advice on its plans for a structural genomics project. The meeting was attended by 12 scientists (the roster is below) and was chaired by Dr. David Eisenberg of the University of California, Los Angeles. These scientists included many of those actively working on both experimental and/or computational structural genomics pilot projects. A broad range of expertise and viewpoints was sought, especially the expertise and viewpoints of scientists with interests in protein structure and folding, as well as those in functional structural biology. Several representatives of NIH institutes and federal agencies also attended. The participants were asked to assist the NIGMS staff in determining goals for the structural genomics project and in preliminary planning for a support program.

The participants discussed the constituent components of the structural genomics project, as well as the project's scientific goals, significance, and likely contributions to science. The various experimental components of the structural genomics project were summarized, especially those focused on high-throughput methods. Attention was also given to computational tasks, with a discussion of the current efforts on protein family classification and target selection that are under way in several laboratories. Results from one of these groups, at the Hebrew University of Jerusalem, were discussed in some detail. This work has investigated the distribution of protein family clusters by size. NIGMS will sponsor a meeting that focuses on these computational aspects in February 1999.

Several participants stressed the need for NIGMS to continue its emphasis on the support of the functional aspects of structural biology, and the comparison between sequence and functional approaches was discussed in detail. The value of including function in target selection was pointed out and will be addressed in the February 1999 meeting. The discovery of protein families of no known function is likely to be an important result of the structural genomics project. Several other concerns were discussed, in particular the effect of the development of this project on the culture of structural biology research, especially in academic settings. It was also pointed out that, in many cases, structural genomics research would not be appropriate for research training projects for graduate students and postdoctoral fellows. Concerns were also expressed that such a large-scale effort would drain resources from the traditional investigator-initiated research grant program. NIGMS director Dr. Marvin Cassman assured the planning group members that the structural genomics project will not compete with the regular research grant program and that the Institute will seek additional funding for the development of this project. Participants generally agreed on the importance of structural genomics research. The importance of international cooperation was discussed. Major efforts are under way in the United Kingdom, Germany, and Japan. Representatives from these countries will be invited to the next NIGMS meeting in structural genomics.

Considerable attention was given to the optimum scale of organization appropriate for pilot projects in structural genomics, and numerous comparisons were made with the development of the Human Genome Project. In many ways, the development of these two applied projects is likely to be similar. The Human Genome Project has now evolved into large centers, with larger levels of organization and correspondingly lower costs. The scientific community has clearly benefited from the results that are emerging from this endeavor. Prior to this planning meeting, NIGMS was considering a program announcement in structural genomics for program projects (P01) to support the pilot projects. Considerable discussion focused on the appropriate goals for these pilots, the costs per structure, and the best level of organization. Since most of the major structural biology laboratories currently are about the size of P01 grants, NIGMS was urged to support pilot studies at a larger level of organization, through research center grants (P50). The Institute was advised to plan for a pilot program of about six research center grants, with a total budget of about $20 million.

On behalf of the participants, Dr. Eisenberg summarized the benefits and goals of the first pilot phase of the project and urged NIGMS to continue the development of a support program in this field. Dr. Eisenberg concluded that: 1) the knowledge from a structural genomics project will be important for the biological sciences, 2) much of the necessary technology has been developed, and 3) pilot projects should be supported to provide further development of experimental and computational technology and knowledge of the appropriate metrics for subsequent large-scale projects. Among the expected benefits of a structural genomics research program are: 1) the development of high-throughput experimental methods; 2) pilot projects that will produce numerous protein structures from several organisms with completely sequenced genomes; 3) Web-accessible database computational techniques; 4) new structure determination methods; 5) fold recognition and assignment methods; 6) knowledge of protein structure, function, folding, and evolution; and 7) progress toward the structures of membrane and complex proteins and molecular machines. Most members felt that structural genomics research was ready for development and recommended that NIGMS undertake the development of this support program.


David S. Eisenberg, Ph.D. (chair)
Molecular Biology Institute
201 MBI Building
University of California, Los Angeles
Los Angeles, CA 90095-1361
Tel: 310-825-3754
Fax: 310-206-3914

Stephen Burley, M.D., Ph.D.
Department of Molecular Biophysics
The Rockefeller University
1230 York Avenue
New York, NY 10021-6399
Tel: 212-327-8836
Fax: 212-327-8337

Wayne A. Hendrickson, Ph.D.
Department of Biochemistry
and Molecular Biophysics
Columbia University
College of Physicians and Surgeons
630 West 168th Street
New York, NY 10032-3795
Tel: 212-305-3456
Fax: 212-305-7379

Liisa Holm, Ph.D. (unable to attend)
European Molecular Biology
Hinxton, Cambridge
CB10 1SD United Kingdom
Tel: 44-0-1223-494-444
Fax: 44-0-1223-494-468

Sung-Hou Kim, Ph.D.
University of California, Berkeley
Calvin Laboratory
Berkeley, CA 94720
Tel: 510-486-4333
Fax: 510-486-5272

Brian W. Matthews, Ph.D.
Institute of Molecular Biology
1229 University of Oregon
Eugene, OR 97403-1229
Tel: 541-346-5151
Fax: 541-346-5870

Rowena G. Matthews, Ph.D.
Biophysics Research Division
University of Michigan
930 N. University, Room 4028
Ann Arbor, MI 48109-1055
Tel: 734-764-9459
Fax: 734-764-3323

Gaetano Montelione, Ph.D.
Rutgers University
679 Hoes Lane
Piscataway, NJ 08854
Tel: 732-235-5321
Fax: 732-235-4850

John Moult, Ph.D.
CARB, University of Maryland
9600 Gudelsky Drive
Rockville, MD 20850
Tel: 301-738-6241
Fax: 301-738-6255

Manuel Navia, Ph.D.
The Althexis Company
P. O. Box 660
Bedford, MA 01730
Tel: 781-674-2077
Fax: 781-674-2077

Paul B. Sigler, M.D., Ph.D.
Department of Molecular Biophysics and Biochemistry (MB&B)
Yale University School of Medicine
260 Whitney Avenue
P.O. Box 208114
New Haven, CT 06520-8114
Tel: 203-432-5425
Fax: 203-432-5239

Steve Smerdon, Ph.D.
National Institute for Medical Research
Protein Structure Room 225
The Ridgeway
Mill Hill
London NW7 1AA England
Tel: 44-0181-959-3666 ext 2533 or 2512
Fax: 44-0181-906-4477

F. William Studier, Ph.D.
Brookhaven National Laboratory
Biology Department
P.O. Box 5000
Upton, NY 11973-5000
Tel: 516-344-3390
Fax: 516-344-6398