Paul F. Agris
Professor, Biological Sciences and Chemistry
B.S. (1966), BIOLOGY AND CHEMISTRY, BUCKNELL UNIVERSITY
PH.D. (1971), BIOCHEMISTRY, MASSACHUSETTS INSTITUTE OF TECHNOLOGY
POSTDOCTORAL FELLOW (1971-1973), YALE UNIVERSITY, DEPARTMENT OF MOLECULAR BIOPHYSICS AND BIOCHEMISTRY
For many years, Dr. Agris has been interested in, and has investigated the basic and applied aspects of RNA chemistry and structure. In particular, he is interested in how the posttranscriptional modifications of RNA alter chemistry and structure for the achievement of function, and how to use this knowledge in biomedicine.
Most recently, his group has shown that modifications pre-structure the anticodon of tRNAs prior to their entry into the ribosome's A-site. The pre-structuring enables some tRNAs to read cognate and wobble codons, and restricts them to their two-fold degenerate codons. In contrast, the modification-dependent pre-structuring of other tRNAs enables them to read their cognate codons and to recognize the three remaining codons of their four-fold degenerate codes. Thus, the modifications expand the capability of these tRNAs to read all codons for their corresponding amino acids. He is now studying those tRNA involved in decoding six-fold degenerate codes.
In collaboration with Dr. Venki Ramakrishnan, the Agris lab has described the structure of tRNA anticodons in the reading of two-fold and four-fold degenerate codons. With high resolution (2.5 Å) x-ray crystallography of the ribosomes 30S subunit, the anticodon/codon interaction can be clearly observed, thus revealing the position and effect of posttranslational modification at the wobble position and 3'-adjacent to the anticodon of tRNA.
In other research, the group is studying the structure/function relationship of mitochondrial tRNAs, the control of gene expression by tRNA, the interaction of HIV with tRNA, and the interaction of aminoglycoside antibiotics with rRNA. Dr. Agris has pioneered a peptide selection technique to study the interactions of proteins with RNA, and modified RNAs, as well.