CAMDEN — General anesthetics put patients “to sleep,” rendering them unconscious and immobile during a surgical procedure. But understanding how they actually work in the brain can be as hazy as patients are when they wake up.
“When anesthetics are at work, you have much less electrical activity going on in your brain,” says Grace Brannigan, an assistant professor of physics at Rutgers University–Camden. “What’s surprising is they cause the effect in a reversible way. Being able to wake up as if nothing happened is what’s remarkable about them.”
Brannigan is part of a collaborative research effort to unlock some of the mysteries behind general anesthetics. The National Institutes of Health is funding the project that includes researchers from the University of Pennsylvania, the University of Pittsburgh, Temple University, Thomas Jefferson University Hospital, and Rutgers–Camden.
“Anesthetics bind to particular proteins in the central nervous system, and we’re looking at where on the proteins the binding occurs,” Brannigan says.
Understanding where and how the drugs bind with the proteins is crucial to improving and developing new anesthetics. Brannigan, who conducts research in Rutgers–Camden’s Center for Computational and Integrative Biology, explains that different proteins in the central nervous system are responsible for transmitting electrical signals, but exactly which proteins the anesthetics target isn’t clear.
“For a lot of drugs, there are one or two proteins they target to cause an effect, but in this case, anesthetics seem to bind and act on many different proteins,” Brannigan explains. “They’re nonspecific and that’s what makes it difficult to understand. We’re trying to narrow down where the drugs are binding on these proteins.”
Using computer simulations and three-dimensional modeling of the proteins, Brannigan is predicting how the anesthetics and proteins interact with each other. Sruthi Murlidaran, a doctoral student in computational and integrative biology at Rutgers–Camden, is working with Brannigan to identify and validate binding sites for the anesthetics using the computer software.
“We’re basically making a movie that simulates this interaction based on what we already know about the physics of the interaction,” Brannigan says. “So, we can see what the laws of physics say about where the binding should best occur.”
Developing new anesthetics that optimizes where the drug binds with the protein in the central nervous system could improve how they work and potentially limit side effects.
The research is being funded by a grant from the National Institutes of Health that is renewable for five years at $98,014 per year.
“In collaborative research like this, you get exposed to many different approaches and viewpoints,” Brannigan says. “In this case, there are people across many disciplines working on this project and it’s very satisfying to know that your work can have an actual effect on the development and improvement of anesthetics.”
A Philadelphia resident, Brannigan earned her bachelor’s degree from Reed College and her doctoral degree from the University of California at Santa Barbara. Rutgers–Camden’s Center for Computational and Integrative Biology combines the expertise of scholars from traditional biomedical disciplines with the analytic methods employed by mathematicians and computer scientists to understand how individual biological systems work.