“We look at a pretty cool class of ion channels that regulates the rhythmic firing of neurons in the heart and the brain,” says Sackler Scholar Hannah DeBerg, Ph.D. She’s measuring the distances between segments in an ion channel — a type of protein structure — in order to understand its function.
The regular way scientists determine protein structure — crystallization — often doesn’t work with ion channels. What’s more, crystallization may not accurately capture the structure an ion channel adopts in the cell membrane. So DeBerg and University of Washington mentors William Zagotta, Ph.D. (physiology and biophysics), and Stefan Stoll, Ph.D. (chemistry), are taking a different tack. Their electron tags act as tiny magnets, and by measuring the pull between the magnets, they can assess the shape of the ion channel and how it works.
“If you know what something really looks like,” says DeBerg, “you can then design small molecules that can bind to it and change its function.” Small molecules that, for instance, could modify the beat of a malfunctioning heart.
This cross-pollination of ideas between the sciences is what the Raymond and Beverly Sackler Foundation intended when they created the Raymond and Beverly Sackler Scholars Program in Integrative Biophysics at the University of Washington. Sackler projects bring together mentors from two disciplines to work with a junior scientist.
“Our foundation is focusing on convergence science to explore the integration of physics, mathematics, chemistry and biology,” says Raymond Sackler, M.D., founder. “The 12 programs we fund, all at leading universities, have the freedom to structure programs that best achieve their goals. The twin-mentor idea at the University of Washington has been a wonderful success.”
Like DeBerg, Sackler Scholar Braden Brinkman, Ph.D., has two mentors. With his mentors, Fred Rieke, Ph.D. (physiology and biophysics) and Eric Shea-Brown, Ph.D. (applied mathematics), and graduate student Alison Weber, Brinkman is constructing models of computational circuits based on the retina: how signals come in, what channels the signals activate, how “noise” in the system affects the process. More broadly, they’re trying to figure out how a neural system receives information and encodes it for the brain, research that someday may have implications for conditions like epilepsy.
“It’s been great having Eric’s and Fred’s perspectives,” says Brinkman. He also enjoys the Sackler Scholars’ lunches, where the fellows talk shop and socialize. “You never know where a great idea is going to come from…I think that’s really important to help foster these ideas,” he says.
“Being able to work on something new — that’s pushing the boundaries and combining techniques and biological systems in new ways — has been a lot of fun,” says DeBerg. “And the Sackler fellowship is really designed to support this type of research.”