This award supports a research visit by Dr. Kay Nakamaye of Gonzaga University to the Max Planck Institute for Experimental Medicine in Goettingen, FRG, to gain experience in the synthesis of nucleotides and to collaborate with Dr. Fritz Eckstein, a leader in the field of nucleic acid chemistry who has pioneered the use of phosphorothioates. Their cooperative research will focus on the use of phosphorothioates in improved procedures for recombinant DNA manipulation; specifically, they are interested in the effect of phosphorothioates incorporated into DNA on cleavage by restriction endonucleases. In previous collaboration, they developed a simple yet efficient method of producing site-specific mutations in isolated DNA fragments or genes. However, one of the limitations of the technique is the need for a specific DNA sequence for the restriction endonuclease to be used, preferably near the site of the intended mutation. They now plan to study class IIS restriction endonucleases as a strategy for directing both the mutation and the position of nicking by the endonuclease. This would make their mutagenesis technique nearly universal for any DNA and DNA sequence. Development of mutagenesis techniques has become essential to investigations in areas such as protein structure-function relationships, gene control and regulation, and DNA/RNA structure. Gene isolation, characterization and manipulation are fundamental components of many biotechnologies. Any further techniques for such work will continue to have great value in basic and applied research.