This award will support collaborative research between Prof. Nancy Kleckner of Harvard University and Dr. Olivier Huisman of the Institut Pasteur, Paris, in the area of genetic analysis of mutant proteins. The objective of this work is the structural and functional dissection of DNA sequences at the ends of a gene segment, which is capable of moving from place to place in the chromosomes of an organism. Such a gene segment is called a transposon; the particular transposon to be studied in this work is called Tn10. Transposition of transposons leads to mutation, and the mutations which occur are to be studied by both genetic and biochemical methods. In the latter, assays for the binding of important proteins to specific DNA sequences should reveal the effects of specific mutations on known processes, and could show new intermediates in the reaction which might accumulate due to intermediate mutational steps. The French collaborators have considerable experience in genetic analysis. Additional materials, as well as expertise in use of an in vitro biochemical system for analysis of the Tn10 transposition, will be brought to the project by the U.S. investigator. The knowledge of complex interactions between DNA and proteins that is expected to result from this research could lead to enhanced progress in our understanding of the processes of the generation, and therefore of alteration, of life itself.
