Paul Schimmel

Paul Schimmel
Born	(1940-08-04) August 4, 1940[1] Hartford, Connecticut
Nationality	American
Fields	Chemistry

Paul Reinhard Schimmel (born 1940) is an American biophysical chemist and translational medicine pioneer.

Life

Paul Schimmel was born in Hartford, Connecticut. He is Ernest and Jean Hahn Professor at the Skaggs Institute for Chemical Biology at The Scripps Research Institute. He used to be the John D. and Catherine T. MacArthur Professor of Biochemistry and Biophysics in the Department of Biology at MIT. Schimmel is author or co-author of more than 450 scientific papers and of a widely used three-volume textbook on biophysical chemistry.^[2] For his achievements and discoveries in scientific research in the biological sciences, Schimmel has been elected member of the American Academy of Arts and Sciences, the National Academy of Sciences, the American Philosophical Society, and the Institute of Medicine. Additional honors related to research and educational achievements include the American Chemical Society’s Pfizer Award in Enzyme Chemistry, the Stein and Moore Award (the highest honor of the Protein Society), the Biophysical Society’s Emily M. Gray Award (co-recipient) for significant contributions to education in biophysics, the Chinese Biopharmaceutical Society’s Brilliant Achievement Award, the Perlman Award (Lecture) of the American Chemical Society, and the Nucleic Acids Award (Lecture) of the Biochemical Society and Royal Society of Chemistry, UK. He has been active in many scientific and academic organizations and committees, including service as Chairman of the Division of Biological Chemistry of the American Chemical Society and as an editorial board member of ten different scientific journals.

For his entire career Schimmel’s research focused on a group of universal enzymes known as aminoacyl tRNA synthetases. The synthetases are believed by many to be among the first enzymes to arise on this planet in the early stages of the evolution of life. These enzymes translate the genetic information in all living organisms. In each cell, there is a separate tRNA synthetase for each of the 20 amino acids. In translating, or interpreting, the genetic material, they catalyze reactions whereby each amino acid is matched with a nucleotide triplet embedded in its cognate tRNA. In this way, the tRNA synthetases establish the rules of the genetic code and, because of this role, tRNA synthetases are essential for all forms of life. Because of decades of research of Schimmel and others, this group of enzymes is now understood to have additional novel functions, and to have deep-rooted connections to human diseases.

Schimmel and his wife Cleo have two daughters and eight grandchildren.

Principal scientific contributions

Correcting mistranslation of genetic material

Schimmel’s laboratory discovered a universal mechanism for correcting errors in the translation (mistranslation) of the genetic material. This mechanism is regarded as one of the most fundamental in biology. Specifically, they discovered an activity in aminoacyl tRNA synthetases that removes an amino acid that has been charged to the wrong tRNA.^[3][4] He later discovered the novel module in synthetases that encodes this deacylase activity.^[5][6] In mammalian cell-based experiments, and in experiments in mice with collaborators at The Jackson Laboratories, they showed that defects in this translational error-correction mechanism gives rise to profound pathologies, including neurodegeneration.^[7][8] These error correction activities were shown to be intimately associated with the beginnings of living organisms.^[9][10][11]

Discovery of the "second genetic code"

Schimmel’s laboratory discovered what has been referred to as a “second genetic code” that relates specific atomic determinants in small RNA substrates to specific aminoacylation.^{[12][13][14][15][16][17][18][19]} This RNA code is considered to give critical insights into the development of the modern genetic code and protein synthesis.

Discovery of the modular design of aminoacyl tRNA synthetases

Schimmel and coworkers were among the first to use genetic methods to establish the modular design of proteins in general and of aminoacyl tRNA synthetases in particular.^{[20][21][22][23]}

Development of expressed sequence tags (ESTs) for genomics

While Schimmel’s research program has largely focused on aminoacyl tRNA synthetases, in a separate line of research published in 1983, Schimmel developed the concept of what are now known as ESTs (expressed sequence tags) and the strategy of shotgun sequencing, approaches that several years later were adopted for the human genome project.^[24] ESTs provide a way to identify all genes that are expressed in a specific tissue, such as muscle, among others. Nature magazine listed Schimmel’s work on ESTs as one of the four key developments that launched the human genome project.^[25]

Expansion of the functional genome

The Schimmel laboratory discovered how tRNA synthetases undergo functional “metamorphosis” in human cells to acquire novel activities in signal transduction pathways ranging from the inflammatory response to angiogenesis.^{[26][27][28][29][30]} This work led to efforts to commercialize applications of human synthetases to treat diseases.

Education

A.B. (1962) Ohio Wesleyan University
Medical Student, (1962–63) Tufts University School of Medicine
Ph. D. (1966) MIT, Department of Biology, mentor: Gordon Hammes

Academic and research appointments

• Postdoctoral Scientist, Department of Chemistry, Stanford University, 1966–67; mentor: Paul Flory.
• Assistant Professor of Biology and Chemistry, MIT, 1967-71.
• Associate Professor of Biology and Chemistry, MIT, 1971-76.
• Visiting Scientist, Department of Biological Sciences, University of California, Santa Barbara, 1975-76.
• Professor of Biochemistry and Biophysics, MIT, 1976–1992.
• John D. and Catherine T. MacArthur Professor of Biochemistry and Biophysics, MIT, 1992- 97.
• Professor and Member, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 1997–2000.
• Ernest and Jean Hahn Professor, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 2001-
• Visiting Professor, Institute for Advanced Study, The Hong Kong University of Science and Technology, 2008-

Editorial boards

Paul Schimmel has served on the editorial boards of the following scientific journals:

• Accounts of Chemical Research, 1988-94.
• Archives of Biochemistry and Biophysics 1976-80.
• Biochemistry, 1988–2007.
• Biopolymers, 1979–1988.
• European Journal of Biochemistry, 1991–1996.
• International Journal of Biological Macromolecules, 1983–1989.
• Journal of Biological Chemistry, 1977-82.
• Proceedings of the National Academy of Sciences, 1993–1999.
• Protein Science, 1991–1994.
• Nucleic Acids Research, 1977-80.
• Trends in Biochemical Sciences, 1984–2010.

Translational medicine contributions

With his longstanding interest in the applications of basic biomedical research to human health, Schimmel holds more than 25 patents and is a cofounder or founding director of several companies. These companies have created FDA-approved medicines and are developing new medicines to treat patients for infections, mental disorders, cancers, diabetes, and inflammatory conditions, and have provided over a thousand jobs in the US and China. Seven of these companies became publicly traded and three were acquired by other companies. Examples of these companies are:

• RepliGen Corporation ^[31]
• Alkermes ^[32]
• Cubist Pharmaceuticals, Inc.^[33]
• Momenta Pharmaceuticals, Inc.^[34]
• Alnylam Pharmaceuticals, Inc.^[35]
• Sirtris, a GSK Company ^[36]
• aTyr Pharma ^[37]

In recognition of the broad impact of his translational medicine activities, he received the Chinese Biopharmaceutical Association’s Brilliant Achievement Award in 2006.^[38] The European-based Science Alliance and Technopolicy Network named Schimmel "Most Entrepreneurial Scientist of USA" in 2007 at a ceremony in Washington DC.^[39]

External links

• Official website

References