The ultimate goal of this research is to visualize, in intact cells, the structure of any gene. When gene expression is regulated at the level of transcription, changes in the structure of the gene are responsible for inducing changes in gene expression. These functional differences in gene structure are initiated and maintained by the interaction of regulatory proteins and chromosomal proteins with the gene, and possibly, by the formation of altered structures within the DNA helix. Dr. Becker is developing a set of photochemical methods, which, when taken together, is allowing one to detect as well as specify those elements of a gene's structure that are responsible for regulating its activity. This approach is based on earlier work which demonstrated that ultraviolet light can detect, at single nucleotide resolution, protein DNA contacts in whole cells. By directly probing gene structure in vivo rather than in vitro, potentially inaccurate or incomplete conclusions regarding the role of gene structure in regulating gene expression will be avoided. The ability to rapidly sequence any gene has revolutionized biology. Here the next level of organization, the structure of the gene, is being attacked. By determining the protein - DNA interactions and altered DNA structures within a gene general organizational principles for rendering the genetic message biologically active, stable, and inheritable will be uncovered.
