Proteins, which regulate the body's cells, must bind to the correct base pairs to function appropriately. They must accurately identify just the right site out of the three billion base pairs of DNA in the human genome. Rather than scan the entire genome for the correct binding site, Tullius and others have hypothesized that markers along the helix help proteins narrow in on their targets. Now Tullius has created a technique to make high resolution images of those markers, and create a clearer picture of just how DNA and proteins work together to regulate life functions.

This "radical" new technique, hydroxyl radical footprinting, is based on an in vitro technique Tullius developed more than fifteen years ago. His original technique, using iron chemistry to produce a hydroxyl radical, is widely used to study protein-DNA complexes in a test tube.

The new technique, developed with support from the NIH, uses ionizing radiation to produce a hydroxyl radical within the cell. Implementing it, Tullius and his team were able to produce a high-resolution image of a protein, known as the bacteriophage lambda repressor, bound to a site on the DNA inside of living E coli cells.

"While much emphasis has been placed on enumerating the proteins encoded by the genome, how gene expression is regulated is at least of equal importance," says Tullius. "Regulation of gene expression is accomplished by proteins which bind to specific DNA sequences nearby genes. Finding out which proteins occupy which DNA binding sites, and under what circumstances, is the essence of the problem." Tullius' footprinting technique provides a direct image of which DNA sites are occupied by protein, and which are empty.