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Simpson Joseph
Biochemistry & Biophysics: ribosome structure, function and dynamics; discovery of novel antibiotics |
| Contact Information |
| Office: UH 4102 |
| Phone: (858) 822-2957 |
| Fax: (858) 534-7042 |
| Email: sjoseph@ucsd.edu |
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| Education and Appointments |
| 1994 |
Ph.D., University of Vermont
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| 1989 |
M.S., Madurai Kamaraj University
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| 1987 |
B.S., Loyola College
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| Awards and Academic Honors |
| 2000 |
Hellman Faculty Fellow |
| 1997 |
American Cancer Society Postdoctoral Fellow |
| 1994-1998 |
Postdoctoral Associate, University of California, Santa Cruz, |
| 1987-1989 |
Department of Biotechnology Merit Scholarship |
| 1984-1987 |
Recipient of Loyola Gold Medal |
| Research Interests |
Translation is the fundamental process by which information encoded in nucleic acid is used to synthesize proteins. Ribosomes are the cellular machines responsible for protein synthesis in all cells. Recent atomic resolution structures of the large and small ribosomal subunits provide a unique opportunity to understand the mechanism by which ribosomes perform the complex task of protein synthesis. One of the crucial functions performed by the ribosome is the iterative movement of the tRNA-mRNA complex, a process called translocation. The molecular basis of translocation is poorly understood. Translocation is catalyzed by an elongation factor (EF-G in E. coli). EF-G is a GTPase and the chemical energy of GTP hydrolysis is coupled to translocation of the tRNA-mRNA complex within the ribosome. Furthermore, the ribosome is a dynamic complex and undergoes large-scale conformational changes during translocation. The goal of my laboratory is to identify the molecular interactions within the ribosome that are essential for translocation.
Ribosomes are the target for inactivation by several classes of antibiotics. Antibiotics such as erythromycin, spectinomycin, viomycin, thiostrepton, and the aminoglycosides specifically inhibit translocation. Antibiotic-resistant strains of bacteria are on the rise, causing a crisis in the management and treatment of these infections throughout the world. Understanding the mechanism of translocation will provide insights for developing more effective antibiotics that target the ribosome of these drug-resistant strains of bacteria.
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Interdisciplinary Specialties: |
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Biochemistry
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Macromolecular Structure
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| Selected Publications |
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Mapping the inside of the ribosome with an RNA helical ruler. With B. Weiser and H. F. Noller. Science 278, 1093 (1997).
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Conformational changes in the ribosome induced by translational miscoding agents. With O. Jerinic. J. Mol. Biol. 304, 707 (2000).
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Identification of molecular interactions between P-site tRNA and the ribosome essential for translocation. With J. S. Feinberg. Proc. Natl. Acad. Sci. USA. 98, 11120 (2001).
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Binding of aminoglycoside antibiotics to the small ribosomal subunit: a continuum electrostatics investigation. With C. Ma, N. A. Baker and J. A. McCammon. 2002. J. Am. Chem. Soc. 124, 1438 (2002).
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All-atom homology model of the Escherichia coli 30S ribosomal subunit. With C. Tung and K. Y. Sanbonmatsu. Nature Structural Biology 9, 750 (2002).
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Universally conserved interactions between the ribosome and the anticodon stem-loop of A site tRNA important for translocation. With S. S. Phelps and O. Jerinic. Molecular Cell 10, 799 (2002).
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Rapid kinetic analysis of EF-G-dependent mRNA translocation in the ribosome. With S. M. Studer and J. S. Feinberg. J. Mol. Biol. 327, 369 (2003).
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