Paul Schimmel
Encyclopedia
Paul Schimmel is an American
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

 biophysical chemist and translational medicine pioneer.

Life

Paul Schimmel was born in Hartford
Hartford, Connecticut
Hartford is the capital of the U.S. state of Connecticut. The seat of Hartford County until Connecticut disbanded county government in 1960, it is the second most populous city on New England's largest river, the Connecticut River. As of the 2010 Census, Hartford's population was 124,775, making...

, Connecticut
Connecticut
Connecticut is a state in the New England region of the northeastern United States. It is bordered by Rhode Island to the east, Massachusetts to the north, and the state of New York to the west and the south .Connecticut is named for the Connecticut River, the major U.S. river that approximately...

. He is currently Ernest and Jean Hahn Professor at The Skaggs Institute for Chemical Biology at The Scripps Research Institute
The Scripps Research Institute
The Scripps Research Institute is an American medical research facility that focuses on research in the basic biomedical sciences. Headquartered in La Jolla, California, with a sister facility in Jupiter, Florida, the institute is home to 3,000 scientists, technicians, graduate students, and...

. He formerly was 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. 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
American Academy of Arts and Sciences
The American Academy of Arts and Sciences is an independent policy research center that conducts multidisciplinary studies of complex and emerging problems. The Academy’s elected members are leaders in the academic disciplines, the arts, business, and public affairs.James Bowdoin, John Adams, and...

, the National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...

, the American Philosophical Society
American Philosophical Society
The American Philosophical Society, founded in 1743, and located in Philadelphia, Pa., is an eminent scholarly organization of international reputation, that promotes useful knowledge in the sciences and humanities through excellence in scholarly research, professional meetings, publications,...

, and the Institute of Medicine
Institute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...

. Additional honors, among others, 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 2 daughters and 8 grandchildren.

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. He later discovered the novel module in synthetases that encodes this deacylase activity. 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. These error correction activities were shown to be intimately associated with the beginnings of living organisms.

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. 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.

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 back 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. 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.

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. This work led to efforts to commercialize applications of human synthetases to treat diseases.

Education

A.B. (1962) Ohio Wesleyan University
Ohio Wesleyan University
Ohio Wesleyan University is a private liberal arts college in Delaware, Ohio, United States. It was founded in 1842 by Methodist leaders and Central Ohio residents as a nonsectarian institution, and is a member of the Ohio Five — a consortium of Ohio liberal arts colleges...



Medical Student, (1962–63) Tufts University School of Medicine
Tufts University School of Medicine
The Tufts University School of Medicine is one of the eight schools that constitute Tufts University. Located on the university's health sciences campus in the Chinatown district of Boston, Massachusetts, the medical school has clinical affiliations with thousands of doctors and researchers in the...



Ph. D. (1966) MIT, Department of Biology, mentor: Gordon Hammes

Academic and Research Appointments

  • Postdoctoral Scientist, Department of Chemistry, Stanford University
    Stanford University
    The Leland Stanford Junior University, commonly referred to as Stanford University or Stanford, is a private research university on an campus located near Palo Alto, California. It is situated in the northwestern Santa Clara Valley on the San Francisco Peninsula, approximately northwest of San...

    , 1966–67; mentor: Paul Flory
    Paul Flory
    Paul John Flory was an American chemist and Nobel laureate who was known for his prodigious volume of work in the field of polymers, or macromolecules...

    .
  • 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
    University of California, Santa Barbara
    The University of California, Santa Barbara, commonly known as UCSB or UC Santa Barbara, is a public research university and one of the 10 general campuses of the University of California system. The main campus is located on a site in Goleta, California, from Santa Barbara and northwest of Los...

    , 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
    The Scripps Research Institute
    The Scripps Research Institute is an American medical research facility that focuses on research in the basic biomedical sciences. Headquartered in La Jolla, California, with a sister facility in Jupiter, Florida, the institute is home to 3,000 scientists, technicians, graduate students, and...

    , 1997-2000.
  • Ernest and Jean Hahn Professor, The Skaggs Institute for Chemical Biology, The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute is an American medical research facility that focuses on research in the basic biomedical sciences. Headquartered in La Jolla, California, with a sister facility in Jupiter, Florida, the institute is home to 3,000 scientists, technicians, graduate students, and...

    , 2001-
  • Visiting Member, Institute for Advanced Study, Hong Kong University of Science and Technology
    Hong Kong University of Science and Technology
    The Hong Kong University of Science and Technology is a public university located in Hong Kong. Established in 1991 under Hong Kong Law Chapter 1141 , it is one of the nine universities in Hong Kong.Professor Tony F. Chan is the president of HKUST...

    , 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
  • Alkermes
  • Cubist Pharmaceuticals, Inc.
  • Momenta Pharmaceuticals , Inc.
  • Alnylam Pharmaceuticals, Inc.
  • Sirtris, a GSK Company
  • aTyr Pharma


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