Dr. Schimmel is now working at both the Florida
and California campuses.
His Florida telephone number is (561) 228-2483
His California telephone number is (858) 784-8970
Department of Chemistry
The Skaggs Institute for Chemical Biology
Faculty, Graduate Program
Institute for Advanced Study, Hong Kong University of Science and Technology
Scripps Florida Campus
Decoding Genetic Information In Translation
The genetic code was established over two billion years ago and became universally adopted by all living organisms. The rules of the code--which relate specific nucleotide triplets to specific amino acids--are established by aminoacylation reactions catalyzed by aminoacyl tRNA synthetases. In these reactions, an amino acid is associated with a specific nucleotide triplet of the genetic code, by virtue of being linked to a specific tRNA that harbors the anticodon triplet cognate to the amino acid. Because of their central role in establishing the rules of the code, the tRNAs are thought to have arisen quite early, perhaps in the context of an RNA world. The synthetases may have been amongst the earliest proteins to appear, perhaps replacing ribozymes that catalyzed the aminoacylation of primordial tRNAs. The Schimmel laboratory is interested in understanding all aspects of these systems.
Our present work focuses on the discovery of the large new biology that flows out of the tRNA synthetases. These enzymes are now known to be secreted, to have nuclear functions, and to pervade most or all parts of human biology with activities that are distinct from their catalytic function of charging tRNA. The laboratory uses methods and logic of molecular and cell biology, chemistry, and structural analysis to more deeply investigate these novel functions that have a fundamental role in maintaining organismal homeostasis, and in developing and regulating nervous, vascular, and immunological systems. The research is leading to the development of a broad new class of therapeutics to treat and cure human diseases.
Ph.D., Biophysical Chemistry, Massachusetts Institute of Technology, 1966
McArthur Professor, MIT; Honors: Alfred P. Sloan Fellow; American Chemical Society Pfizer Award in Enzyme Chemistry; Elected Fellow, American Association for Advancement of Science; Elected Fellow, American Academy of Arts and Sciences; Elected Member, National Academy of Sciences, Doctor of Science (Honorary), Ohio Wesleyan University; Elected Member, American Philosophical Society; Elected member, Institute of Medicine of the National Academy of Sciences; Biophysical Society Emily M. Gray Award (co-recipient), Stein and Moore Award (The Protein Society), Chinese Biopharmaceutical Association Brilliant Achievement Award, Frank Westheimer Medal (Harvard University), Nucleic Acids Award (British Biochemical Society and Royal Society of Chemistry), David Perlman Award (American Chemical Society), Editorial Boards: Accounts of Chemical Research; Archives of Biochemistry and Biophysics; Biochemistry; Biopolymers; European Journal of Biochemistry; International Journal of Biological Macromolecules; Journal of Biological Chemistry; Proceedings of the National Academy of Sciences; Protein Science; Nucleic Acids Research; Trends in Biochemical Sciences.
For a complete list of publications: http://www.scripps.edu/schimmel/publications_schimmel.html
Guo, M. and Schimmel, P. (2013). Essential Ex-translational functions of tRNA synthetases. Nature Chem. Biol. 9: 145-153.
Zhou, H., Sun, L., Yang, X.-L., and Schimmel, P. (2013). ATP-directed capture of bioactive herbal-based medicine on human tRNA synthetase. Nature 124: 121-125.
Xu, Z., Wei, Z., Zhou, Jie J., Ye, F., Lo, C. W. S., Wang, F., Wu, J., Lau, C. C. F., Nangle, L. A., Chiang, K. P., Yang, X.-L., Zhang, M., and Schimmel, P. (2012). Internally deleted human tRNA synthetase suggests evolutionary pressure for repurposing. Structure 20: 1470-77.
Sajish, M., Zhou, Q., Kishi, S., Valdez Jr, D. M., Kapoor, M., Guo, M., Kim, S., Lee, S., Yang, X-L. and Schimmel, P. (2012). Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-gamma and p53 signaling. Nature Chem. Biol. 8: 547-554.
Guo, M. and Schimmel, P. (2011). Structural Analysis Clarifies the Complex Control of Mistranslation by tRNA Synthetases. Current Op. Struct. Biol. 22:1-8.
Guo, M., Yang, X.-L., and Schimmel, P. (2010). New functions of aminoacyl tRNA synthetases beyond translation. Nature Rev. Mol. Cell. Biol. 11: 668-674.
Guo, M., Chong, Y. E., Yang, X.-L., and Schimmel, P. (2009). The C-Ala domain brings together editing and aminoacylation functions on a single tRNA. Science 325: 744-747.
Guo, M., Chong, Y. E., Shapiro, R., Beebe, K., Yang, X.-L., and Schimmel, P. (2009). Paradox of Mistranslation of Serine for Alanine Caused by AlaRS Recognition Dilemma. Nature 462: 808-812.
Beebe, K., Mock, M., Merriman, E., and Schimmel, P. (2008). Distinct domains of tRNA synthetase recognize the same base pair. Nature 451: 90-94