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 Institute201 MBI BuildingUniversity of California, Los AngelesLos Angeles, CA 90095-1361Tel: 310-825-3754Fax: email@example.com
Stephen Burley, M.D., Ph.D.Department of Molecular BiophysicsThe Rockefeller University1230 York AvenueNew York, NY 10021-6399Tel: 212-327-8836Fax: firstname.lastname@example.org
Wayne A. Hendrickson, Ph.D.Department of Biochemistryand Molecular BiophysicsColumbia UniversityCollege of Physicians and Surgeons630 West 168th StreetNew York, NY 10032-3795Tel: 212-305-3456Fax: email@example.com
Liisa Holm, Ph.D. (unable to attend)European Molecular BiologyLaboratory-EBIHinxton, CambridgeCB10 1SD United KingdomTel: 44-0-1223-494-444Fax: firstname.lastname@example.org
Sung-Hou Kim, Ph.D.University of California, BerkeleyCalvin LaboratoryBerkeley, CA 94720Tel: 510-486-4333Fax: email@example.com
Brian W. Matthews, Ph.D.Institute of Molecular Biology1229 University of OregonEugene, OR 97403-1229Tel: 541-346-5151Fax: firstname.lastname@example.org
Rowena G. Matthews, Ph.D.Biophysics Research DivisionUniversity of Michigan930 N. University, Room 4028Ann Arbor, MI 48109-1055Tel: 734-764-9459Fax: email@example.com
Gaetano Montelione, Ph.D.Rutgers UniversityCABM679 Hoes LanePiscataway, NJ 08854Tel: 732-235-5321Fax: firstname.lastname@example.org
John Moult, Ph.D.CARB, University of Maryland9600 Gudelsky DriveRockville, MD 20850Tel: 301-738-6241Fax: email@example.com
Manuel Navia, Ph.D.The Althexis CompanyP. O. Box 660Bedford, MA 01730Tel: 781-674-2077Fax: firstname.lastname@example.org
Paul B. Sigler, M.D., Ph.D.Department of Molecular Biophysics and Biochemistry (MB&B)Yale University School of Medicine260 Whitney AvenueP.O. Box 208114New Haven, CT 06520-8114Tel: 203-432-5425Fax: email@example.com
Steve Smerdon, Ph.D.National Institute for Medical ResearchProtein Structure Room 225The RidgewayMill HillLondon NW7 1AA EnglandTel: 44-0181-959-3666 ext 2533 or 2512Fax: firstname.lastname@example.org
F. William Studier, Ph.D.Brookhaven National LaboratoryBiology DepartmentP.O. Box 5000Upton, NY 11973-5000Tel: 516-344-3390Fax: email@example.com
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