Ben Kuznets-Speck, a senior in the college’s joint mathematics and physics program, was one of 240 undergraduates across the country selected as 2017 Goldwater Scholars. Photo by Mike Sands.
Ben Kuznets-Speck does some of his best thinking in the water. During his high school years in Skokie, Ill., he was a competitive swimmer, and as a senior at Case Western Reserve, he still hits the pool four to six times a week. Now, though, doing laps is more of a meditative experience, a chance to free up mental space and mull over difficult research.
“It’s the closest I can come to flying. It helps me focus, clear my head and think about new ideas,” he says.
Kuznets-Speck takes all the mental processing time he can get. As a student in the joint mathematics and physics program in the College of Arts and Sciences, he has devoted himself to the complex field of theoretical biophysics—a mathematical discipline that seeks to explain the behaviors of biological systems by distilling them down to a set of basic rules.
Take atoms, for example. Zoom in far enough on any solid object, and you’ll see a messy, burbling cloud of atomic particles. On the surface, it seems like complete chaos, but inside that cloud, there’s hidden simplicity.
“All of those atoms are moving in a straight line. When they’re hit by another atom, they start moving in another straight line, just in a different direction,” says Kuznets-Speck. “It’s a simple rule, but when you have lots of particles doing that, it starts to look very complicated.”
The ability to find a set of mathematical rules like these—to reduce a system to a simple and elegant equation—is key to understanding almost any thorny problem, Kuznets-Speck says. For him, though, it’s also just plain fun.
“I guess I’ve always loved the art of calculation, of starting with something messy and disgusting, and beating it down into something simple and beautiful,” he says. “It’s like detective work, in a sense. You’re often looking for an answer on a problem that no one else has ever done.”
His penchant for tackling difficult problems hasn’t gone unnoticed. Last spring, in recognition of his “exceptional promise” as a student, Kuznets-Speck was named a Goldwater Scholar, a prestigious honor for undergraduates intending to pursue research careers in mathematics, engineering or the natural sciences. He was recommended for the scholarship by two of his faculty mentors in the Department of Physics: Professor Harsh Mathur and Associate Professor Michael Hinczewski. Kuznets-Speck has been a member of Hinczewski’s research group in theoretical biophysics since 2015.
“It’s been wonderful to see him mature as a scientist over the last two years, and take the initiative in shaping research projects,” Hinczewski said when the award was announced last spring by the Office of Undergraduate Studies. “I’m so happy that his work and talents have been highlighted by a Goldwater Scholarship, and I hope this bodes well for his future trajectory in science.”
If his current research is any indication, that trajectory is soaring. Along with Hinczewski, Kuznets-Speck is using mathematical tools to study the collections of molecules that make up our cells and tissues. Figuring out the rules that govern how those molecules work together could shed light on some of the body’s essential chemical functions.
Muscle, for instance, is built up of microscopic cellular fibers that expand and contract to cause almost every motion our bodies make. Yet the real stars of the show are the individual molecules within each fiber. At that small scale, muscle motion is governed by structures called “molecular motors.” These long protein filaments act as tiny levers, contracting gently whenever other proteins bind with them. Each “lever” exerts an exceedingly tiny force. But when multiplied over trillions of molecules, this force adds up to a flexed muscle.
From left: Michael Hinczewski welcomed Ben Kuznets-Speck into his theoretical biophysics research group in 2015, and they have collaborated ever since. Harsh Mathur, Kuznets-Speck’s advisor, suggested that they work together. Photo by Mike Sands.
With the right mathematical equation, Kuznets-Speck says, it is possible to model and predict how these fundamental building blocks work. The problem, however, is that it’s not quite as simple as guessing whether a molecular motor is on or off at a given time. Any movement those structures make is the end result of dozens of individual chemical reactions that control how and when they will contract. For a muscle fiber to flex in concert with its neighbors, those reactions have to happen in the right place, at the right time—so predicting how a single molecule will behave usually requires complex statistics.
“Biology is all probabilistic,” Hinczewski says. “Chemical processes in the body aren’t like flipping a switch, where you have the same result every time. Sometimes two proteins can’t find each other, or don’t react with each other in the right way, so there’s a lot of noise in your data. Theoretical biophysics lets us sort out patterns in that noise, build mathematical models of them and, in doing so, learn something about how biology functions.”
The process that triggers molecular motors, called “cellular signaling,” goes far beyond just moving muscles, Hinczewski adds. Similar chemical reactions control nearly every other cellular function, from absorbing nutrients to fighting toxins. The mathematical tools that Hinczewski and Kuznets-Speck are developing may help describe how those signals work.
“Say you have a toxin that hits receptors on a cell membrane. It will immediately trigger a series of chemical reactions that propagate from the cell membrane to the nucleus,” says Kuznets-Speck. “The nucleus then decides, ‘What genes should I activate? Do I need to combat this thing as a toxin, or receive it as a nutrient?’ Essentially, it’s like a huge biological game of telephone, as one reaction passes the signal on to the next. What’s really interesting is that these reactions are very imprecise; there are a lot of errors in the system. So we want to know: How do you quantify that error? What are the reaction rates for different levels of the cascade? How do you figure out the amount of info that is sent reliably?”
In another area of inquiry, Hinczewski and Kuznets-Speck are engaged in research that may ultimately prove useful in devising new treatments, including individualized therapies, for genetic disorders such as hypertrophic cardiomyopathy (HCM). This disease is caused by mutations that alter the function of motor proteins in heart muscle. As a result, heart tissue thickens, leading to arrhythmia and, eventually, sudden cardiac arrest. Hinczewski and Kuznets-Speck are focusing on how the consequences of the genetic mutations play out at the level of individual molecules.
If this doesn’t strike you as a typical college research experience, you’re not alone. Hinczewski says his work with Kuznets-Speck goes well beyond most undergraduate mentorships.
“It’s not like you’re the boss telling him what to do. It’s a collaboration. We’re both trying to solve the same problems, both offering solutions. He brings new ideas to the table all the time,” Hinczewski says. “I’ve never had that sort of collaborative experience with an undergrad before.”
None of this surprises Harsh Mathur. As Kuznets-Speck’s academic advisor, Mathur was the one who first suggested he meet Hinczewski. Within weeks, Kuznets-Speck found himself captivated by theoretical biophysics.
“I was drowning in the work for about six months before I started to get the hang of it,” he says. “There were a lot of late nights. I would go home and beat my head against a problem for hours. It was painful, but when that wall finally budges and you get a clear answer, it’s addictive.”
That tenacity, Mathur says, is something he sensed early. Once Kuznets-Speck takes on a problem, he explores it from all angles, doing original research, combing through academic journals and making connections well outside the range of those covered in his courses.
“He works like a real scientist,” says Mathur, who has also recruited Kuznets-Speck as a research collaborator; they are applying statistical frameworks to predict the spread of viral epidemics. “Ben doesn’t come in saying, ‘Here’s what I know, now what can I do with it?’—there’s no hand-holding. He does what he needs to do to get the job done.”
For his part, Kuznets-Speck is grateful to his mentors for their personal attention and guidance on these projects. “Anytime I get a chance to sit down and talk one on one with Harsh or Mike, I take something new away from the conversation,” he says. “They’ve given me so much insight, both scientifically and otherwise.”
David Levin is a freelance science writer based in Boston.