9412482 Agris This US-Poland Research project between Dr. Paul F. Agris of North Carolina State University, and Dr. Andrzej Malkiewicz of the Technical University of Lodz, is on "Design and Chemistry of Modified Nucleosides for Nucleic Acid Synthesis." How modified nucleoside chemistry, structure and dynamics relate to function of RNAs, but also DNA, is not understood. Once understood, even for a small number of base modified nucleosides, this varied collection of chemistries and structures can be applied to the design and engineering of molecules important to biology and medicine. The evolution of the more than 80 modified nucleosides in RNAs and DNA is connected with their site-selected positioning and altering of nucleic acid chemistry and structure; the potential to accomplish this is as varied as are the chemistries and structures of the modifications. The cooperating investigators will develop new technologies and methods for studying the site-selected incorporation of both native and non- native modified and stable-isotope labeled nucleosides in RNA and DNA, applicable, initially, to fundamental nucleic acid biochemistry (molecular evolution, nucleic acid structure). The mutual benefit from the cooperative project derives from the perfect complementary experiences of the two investigators. Dr. Malkiewicz is broadly experienced in the organic chemical syntheses, chemistry and analyses of modified nucleosides and small oligomers containing modified nucleosides; whereas Dr. Agris is broadly experienced in the biosynthesis and analyses of both the structures and functions of modified nucleosides in RNA. This project in biochemistry fulfills the program objective of advancing scientific knowledge by enabling leading experts in Poland and the United States to combine complementary talents and pool resources in areas of strong mutual interest and competence. ***