Faculty Lecture Series

When	Wednesday, January 13, 2009 5 PM - 6 PM
Where	Valerie Timken Amphitheater Green Hospital
Who		Paul Schimmel, Ph.D. Ernest and Jean Hahn Professor of Molecular Biology and Chemistry Professor, Department of Molecular Biology Member, Ths Skaggs Institute for Chemical Biology
Topic	"Connecting Genetic Code Development to Novel Functions with Medical Applications"
	The aminoacyl tRNA synthetases were at the heart of the establishment of the genetic code. The modern code, established billions of years ago, was so robust that it eliminated all competing codes and, while conceptually simple, had the capacity to generate the vast complexity of all living species. The tRNA synthetases—one for each amino acid—catalyze the 20 aminoacylation reactions that define the algorithm of the genetic code. As we now understand, they also do far more through their acquisition (throughout evolution) of novel, non-aminoacylation functions. Significantly, certain non-aminoacylation functions were needed to initiate life. These early non-aminoacylation functions are now understood to be relevant to neurological disease. The later acquisition (in evolution) of even more novel functions went lockstep with the expansion of the diversity and complexity of emerging organisms. Thus, new human biology with medical applications is now being conceptually connected to the development of the genetic code.
Selected Publications
	Kapoor, M., Otero, F. J., Slike, B. M., Ewalt, K. L., and Yang, X.-L. (2009). Mutational separation of aminoacylation and cytokine activities of human tyrosyl-tRNA synthetase. Chem. and Biol. 16: 531–539.
	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.
	Zhou, Q., Kapoor, M., Guo, M., Belani, R., Xu, X., Kiosses, W. B., Hanan, M., Park, C., Armour, E., Do, M.-H., Nangle, L. A., Schimmel, P., and Yang, X.-L. (2010). Orthogonal use of a human tRNA synthetase active site to achieve multifunctionality, Nature Str. Mol. Biol, in press (published on-line December 13, 2009).
	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.