The Tower of Babel. That's what you often find when you put biologists and physicists together. Biologists, possessing a rich vocabulary of molecular nomenclature and conditions, are regarded by physicists with bewilderment. And the physicist's minimalistic terminology, which strives to describe the universe and everything in it in terms of a few forces and particles, seems to biologists incomprehensibly sparse.
But communicative sparks between the two groups can, at times, be observed. Take Prof. Joel Stavans, a physicist, and Dr. Opher Gileadi, a biologist. They are working side by side to decipher a language that is equally enigmatic to both: the DNA molecule's secret code of life.
Unlike biologists who have focused mainly on identifying the genes lodged in the DNA, Stavans of the Physics of Complex Systems Department and Gileadi of the Molecular Genetics Department peer at DNA from a different angle. What happens when you stretch a DNA molecule, when does the DNA fold, and what effect does this have on gene expression?
Biologists have found that a molecule in our body that is a motor, scanner and printer all in one, plays an important role in gene expression. Called RNA polymerase, this multitalented molecule seats itself on one end of a gene. It then travels along the gene, producing a "print-out" of the genetic sequence. This printout is in fact a molecule called RNA. It is carried from the DNA to a "protein factory" which, reading the printout, manufactures the proper protein.
But what is it that determines on which gene the machine will seat itself, i.e., what determines which gene will be expressed at a particular time? DNA contains certain sections that are "instruction manuals": they specify when and where RNA polymerase should start its work. These sections (called regulatory sequences) are placed in between the genes, which themselves constitute only a small portion of the DNA.
At times, an instruction manual can be positioned at a great distance from the gene that it wants to activate. To cause the gene's activation, it must get closer to the gene. Biologists have found that this often occurs by the looping of intervening DNA (much like the "loop" that is formed when bringing our forehead to our otherwise faraway knees). Naturally, the forces and factors that can influence DNA looping are of critical importance for the function of genes.
"To study looping, we are looking for ways to induce the DNA to loop," says Stavans. One known method is to introduce a special protein into the DNA's environment. It is a DNA-binding protein, meaning that it binds to the DNA at certain sites. Stavans and Gileadi inserted into the DNA two sites for which the protein has an affinity. The protein, spotting two sites that it "liked," simultaneously attached itself to both sites and brought them together in a loop.
Though scientists cannot see the looping itself since it is much too small, they have developed a method providing them with evidence of looping. One end of the DNA strand is attached to a surface and the other to a bead large enough to be detected using a microscope. When a loop is formed, a decrease in the distance between the bead and the surface can be observed. Stavans and Gileadi are using this method to understand the physical rules that govern looping and the factors that affect it in living cells.
Says Stavans: "Technology has brought biology closer to physicists. Now it is possible to analyze one strand of DNA, a concept attractive to a physicist, who usually strives to reduce complex systems to their simple components."