News and Publications
The Skaggs Institute For Chemical Biology
Scientific Report 2001-2002
Richard A. Lerner, M.D.
As I reflect on the year's accomplishments of members of The Skaggs Institute
for Chemical Biology at The Scripps Research Institute, I am struck anew by the
scope, depth, and extraordinary quality of scientific inquiry here. Most impressive
is the eclectic yet synergistic nature of the faculty; although the members vary
greatly in age, background, research interests, and scientific sensibility, their
bond as part of the Skaggs Institute has created a unique opportunity for scientific
collaboration and achievement.
Of course, we were delighted to share in the celebration for Kurt Wüthrich,
member of the Skaggs Institute, Cecil H. and Ida M. Green Visiting Professor
of Structural Biology at TSRI, and professor of biophysics at Eidgenössische
Technische Hochschule Zürich, when he was awarded the 2002 Nobel Prize in
Chemistry for applying the technique of nuclear magnetic resonance (NMR) to solving
the structures of biological macromolecules. Dr. Wüthrich's recognition
followed that of K. Barry Sharpless, member of the Skaggs Institute and W.M.
Keck Professor of Chemistry at TSRI, who was awarded the 2001 Nobel Prize in
Chemistry for the development of catalytic asymmetric synthesis. We are proud
of the accomplishments of these eminent scientists and are humbled by their unwavering
commitment to the scientific enterprise.
Dr. Wüthrich is at the forefront of his field as he continues to push
the boundaries of structural biology in new and important ways. He pioneered
using NMR to determine the structure of biological macromolecules, allowing scientists
to "see" what the molecules look like, study and probe their structures, and
design drugs to inhibit them. Specifically, Dr. Wüthrich was cited for his
work in the development of NMR spectroscopy for determining the 3-dimensional
structure of biological macromolecules in solution.
In 1982, Dr. Wüthrich's group published a series of articles that outlined
a framework for NMR determination of protein structure. In 1984, he published
the first protein structure determined by using NMR: that of the protein bull
seminal protease inhibitor. He is the author of the definitive book on the method: NMR
of Proteins and Nucleic Acids.
Dr. Wüthrich has solved more than 50 novel NMR structures of proteins
and nucleic acids, including those of the immunosuppression system cyclophilin
Acyclosporin A, the homeodomain operator DNA transcriptional regulation
system, and murine, human, and bovine prion proteins. He has also solved the
structures of numerous pheromones from Mediterranean sea creatures and pheromone-binding
proteins from other organisms. In addition, he has been examining ways to solve
the structures of membrane proteins, which are some of the least solved of all
the relevant structures in biology.
Most recently, Dr. Wüthrich pioneered the new technique of transverse
relaxation-optimized spectroscopy NMR (TROSY), which extends several-fold the
size limit of structures that can be solved with NMR. With this technique, scientists
can elucidate many important biological structures, such as large proteins and
protein-protein, protein-DNA, and protein-lipid complexes, that are impossible
to investigate by using conventional NMR.
He has also developed other techniques, such as cross-correlated relaxation-enhanced
polarization transfer. Using this technique in combination with TROSY, scientists
can examine very large structures, including ones with molecular mass as large
as 1 million daltons.
Since his affiliation with TSRI in 2001, Dr. Wüthrich has been collaborating
with the Joint Center for Structural Genomics, a $30-million effort to develop
high-throughput technology that could someday support efforts to catalog the
structures of all proteins in the human body. The center is a multi-institution
consortium funded by the National Institutes of Health and led by TSRI professor
Ian Wilson. Dr. Wüthrich is using NMR as a screening tool to evaluate the
quality of protein preparations produced by the automatic procedures. This research
could have a major impact on the quality of the overall effort.
Many other members of the Skaggs Institute were also recognized by their
peers for scientific excellence. In a list from ISI Essential Science Indicators,
5 investigators were ranked among the top 100 most-cited researchers in the field
of chemistry for the past decade: K.C. Nicolaou, Chi-Huey Wong, K. Barry Sharpless,
Dale Boger, and Julius Rebek, Jr. On an organizational level, TSRI was ranked
second in the world among high-impact institutions in chemistry. Dr. Wong was
elected to membership in the National Academy of Sciences, Dr. Nicolaou received
the Tetrahedron Award, Kim D. Janda was elected a fellow of the American Association
for the Advancement of Science, Albert Eschenmoser received the Oparin Medal,
Dr. Rebek won the Chemical Pioneer Award, and Dr. Wilson was elected to the American
Academy of Arts and Sciences. In addition, Ben Cravatt was named one of the country's
top 100 young innovators by Technology Review, the magazine of the Massachusetts
Institute of Technology; Dale Boger received the Janssen Award; and I was given
the Presidential Medal from the University of California and an honorary degree
from Northwestern University.
Once again, we had another extraordinary year of research accomplishments,
all of which were made possible by the vision and outstanding generosity of the
Skaggs family and The Skaggs Institute for Research. Few institutions in the
world are blessed with friends such as the Skaggs family, who understand the
value of the often painstaking, deliberate, complex, and exciting work of early-stage
biomedical research. Only by reaching a profound understanding of the basic mechanisms
that underlie human health and disease can we discover new ways to alleviate
human suffering. To alleviate human suffering is the goal and mission of The
Skaggs Institute for Chemical Biology, and I am secure in the knowledge that
we are making great strides forward.