Science as a Human Endeavor: How biophysics is pushing the boundaries of science

(Shixiao Yu • The Student Life)

In the basement of the Estella Laboratory at Pomona College, the newly established McCluskey Lab is pushing the boundaries of biophysics — exploring the microscopic forces that shape life itself.

As a biophysicist in the lab, I blend principles from physics — such as energy, motion and forces — with biology to understand how physical laws govern the behavior of biological molecules like proteins and DNA.

Assistant professor of physics and astronomy Kaley McCluskey, who leads our lab, explained our research.

“[It] integrates a wide variety of disciplines in both physics and biology, including molecular biology, polymer physics, optics and recently, even machine learning,” McCluskey said. 

By drawing from these diverse fields, we are pushing the boundaries of scientific discovery. My labmate Jacob Zhang PO ’27 aptly explained the discipline.

“In the basement of the Estella Laboratory at Pomona College, the newly established McCluskey Lab is pushing the boundaries of biophysics — exploring the microscopic forces that shape life itself.”

“If biology, chemistry and physics are all ‘working together’ inside our bodies, why shouldn’t we work together in the lab? I propose a new Pomona College campaign called ‘Build The Tunnel’ to fund the construction of a tunnel between Estella and Seaver,” Zhang said.

One exciting project we are working on is studying a critical process in SARS-CoV-2, the virus responsible for COVID-19, called ribosomal frameshifting. This process allows the virus to produce the proteins it needs for survival by causing its protein-making machinery to pause and shift slightly during the translation of its genetic code.

To study this, we use tools such as magnetic tweezers and a total internal reflection fluorescence (TIRF) microscope, the latter of which we built ourselves. Assembling the microscope required careful attention to ensure the light was properly directed. This step was critical because the accuracy of the setup determined how clearly the tiny molecules we’re studying could be observed.

The process took hours over many weeks but we managed to stay energized. One of my favorite moments in the lab was when we named the lasers in the microscope after Star Wars characters: Yoda (green), Princess Leia (infrared) and Darth Plagueis the Wise (red).

Riley Foard PO ’26, a student in Pomona’s 3-2 Plan in Engineering Program who helped build the microscope with me, shared how he first became interested in biophysics.

“Although my last formal biology class was six years ago, Kaley’s research on biophysics, particularly TIRF microscopy, was just really, really cool,” he said. “I remember telling her, ‘I haven’t taken a bio class since my sophomore year of high school,’ to which she responded, ‘Same!’”

During the building process of the microscope, we faced numerous challenges that could not be solved by any one person alone. Zhang recalled struggling for days to drill precise holes into glass with a laser cutter.

“After exhausting all options, I realized I needed help,” he said. It was then that he turned to a chemist with an underwater drill that produced the perfect holes. This moment was a reminder that sometimes the key to solving a problem is recognizing when to ask for help.

This collaborative spirit was a driving force throughout the entire building of the microscope. Our excitement peaked when we took our first image with it.

“[It] meant so much,” Riley said. “I remember FaceTiming our [former] senior thesis student, Yaru Luo PO ’24, who was on a grad school tour at the time, as we all crammed around the image on our computer. Seeing a concrete result of our tedious optical designs was incredibly fulfilling.”

Once the TIRF microscope was built, we were eager to begin using it to study the frameshift element (FSE) in SARS-CoV-2’s RNA. Imagine trying to manipulate a single strand of spaghetti without breaking it — that’s essentially what we were doing with molecules far smaller than the width of a human hair. Using magnetic tweezers, we pulled and stretched the FSE to observe how it folds and changes shape under different conditions.

But before we could study the FSE, we had to build it. Constructing a biological molecule is no simple task. It involves synthesizing specific RNA sequences, which requires knowledge of molecular biology.

Isabel Burger PO ’25, a molecular biology major working on the FSE for her senior thesis, has spent weeks managing these sequences.

“The FSE project has involved a lot of troubleshooting and those challenges have made me more aware of the perseverance and focus required for long-term research,” she said.

Meanwhile, the other senior thesis student in the lab, Nhi Doan PO ’25, is working on optics and machine learning in the microscope that will improve our ability to capture images of molecules more efficiently. Traditional microscopy struggles to detect multiple molecules emitting similar colors, but Nhi’s work with machine learning will help us capture clearer images without extra equipment.

“While I’m smitten with optics, I also find myself wondering about the biological microcosmos our microscope will help unravel,” Nhi said.

As we continue our work on the FSE, we’re excited to explore how it switches between two distinct shapes. By applying different forces with magnetic tweezers, we can observe how the FSE behaves in each shape. This knowledge could lead to better antiviral treatments and deepen our understanding of how life’s basic molecular processes work.

“I’ve worked with RNA, TIRF microscopy and magnetic tweezers before, but never all three at once,” McCluskey said.

Science is collaborative, not a solitary pursuit. Alone, we would have struggled, but together, we’re doing biophysics.

At the McCluskey Lab, we’re integrating interdisciplinary perspectives to tackle big questions, one force at a time. We’re not just uncovering the molecular mechanics that shape life, we’re helping to redefine how scientific discovery happens in the 21st century.

Gabriel Brenner PO ’26 loves exploring the human aspects of science.

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