Molecular disturbance
By Lydialyle Gibson
Photography by Lloyd DeGrane
For all that science has learned about complex biological processes—the production of enzymes, the secretion of hormones, the function of proteins, the expression of genes—large questions remain mostly unanswered. Among them: how do molecular interactions enable those processes? What exactly happens among atoms and molecules that gives rise to a protein or an enzyme or releases a hormone? Four Chicago scientists are working toward an answer, with the hope of applying it to insulin-secreting pancreas cells in diabetes patients.
With a $1 million grant from the W. M. Keck Foundation, endocrinologist Louis Philipson, PhD’82, MD’86, and chemists Aaron Dinner (standing); Norbert Scherer, SB’82, (seated); and Rustem Ismagilov are developing a technique they call “chemical perturbation spectroscopy,” using chemical disruptions to elucidate molecular dynamics. The idea arose in part from a collaboration between Dinner and Scherer. In a 2009 study published in the Journal of Physical Chemistry B, they discovered odd, hidden dynamics in a large RNA molecule after introducing chemical pulses to the solution surrounding it. Rather than move slowly, as they expected, the molecule behaved “as though something was driving it,” Dinner says.
Optical, magnetic, and spectroscopic perturbations are standard ways to explore molecular interactions, and Dinner and Scherer realized that a chemical version of the technique could open a new avenue to studying cellular dynamics. The method may permit the researchers to “rewire” the regulatory circuitry of insulin-secreting pancreatic beta cells, which are involved in type-2 diabetes. “We expect to be able to target certain cell functions,” Scherer says, “and, let’s say, increase insulin output from the beta cells.” More broadly, the scientists want chemical-perturbation spectroscopy to be a widely used tool for probing the collective mechanisms of many types of molecular networks—and, ultimately, learning to control cell function and behavior.