Biophysical Society Bulletin | October 2023

Biophysicist in Profile

Susy C. Kohout Area of Research Membrane proteins with a focus on the interface between the electrical and chemical signaling of the cell

Institution Cooper Medical School of Rowan University

At-a-Glance

Susy C. Kohout , Associate Professor in the Biomedical Science Department at Cooper Medical School of Rowan University, began to love science starting in high school when she took her first chem istry class. Her passion for chemistry led her to pursue a bachelor’s degree in organic chemistry at the California Institute of Technology, where she also discovered biophysics in her senior year. She continued her education, earning a PhD at the University of Colorado Boulder in biochemistry with a certificate in biophysics. She now specializes in understanding how electrical signaling is translated into chemical signals inside cells.

Susy C. Kohout

Susy C. Kohout grew up in Bethesda, Maryland, but was born in the Dominican Republic. Her family immigrated to the Unit ed States when she was 14 months old. Her father is from Argentina and her mother is from Germany. She and her sisters were all born in different countries. “My father got his PhD in Agricultural Economy,” she says, “but if he had had more choic es, he would have been an engineer. My oldest sister is also a scientist in biotech.” “My interest in combining electrical and chemical signaling started back in undergrad when I took an electrophysiology lab with Dr. Henry Lester . I already knew that I loved the chemistry side, but cell signaling, and membrane potential, were new and exciting,” she explains. “I did a short postdoc with my PhD advisor, Dr. Joe Falke , working on bacterial chemotaxis,” Kohout shares. “My main postdoc was in Dr. Udi Isacoff ’s lab working on a newly discovered voltage regulated protein, the voltage sens ing phosphatase (VSP). Before VSP, only channels were thought to be controlled by voltage sensing domains (VSDs). VSP proved that VSDs are truly modular and can even control an enzyme. Specifically, VSP has direct control over phosphatidyli nositol phosphate (PIP) signaling cascades by changing the PIP concentrations in a voltage-dependent manner.” She adds, “The discovery of VSP was perfect timing for me since VSP uses the type of signaling that interests me. During my postdoc, I identi fied a mechanism for VSD coupling to the enzyme and discov ered that this coupling is potentially regulated by substrate and modulates enzyme activity. These findings paved the way for a structural analysis where I worked with structural biologists, Dr. Lijun Liu and Dr. Dan Minor , who solved several different crystal structures of the cytosolic phosphatase domain of VSP.” Building on those discoveries, Kohout helped generate models of activity derived from those structures and then tested those models using activity assays in live cells. Those activity assays revealed that the VSP mechanism of coupling is analogous to channel gating. She also determined that VSP can function as a monomer with voltage changes inducing a series of conforma tional changes that affect enzymatic activity.

Kohout is currently an Associate Professor in the Biomedical Science Department at Cooper Medical School of Rowan Uni versity (CMSRU). Her lab is split into two main areas: biophysics and physiology. She explains, “On the biophysics side, there’s a lot we don’t understand about how VSP works. Our current focus is on how dimerization impacts function. While I showed that VSP functions as a monomer during my postdoc, once I started my own lab, we discovered that VSP can also dimerize in a concentration-dependent manner. Oligomerization is well known to change how enzymes function, and we believe VSP is no different. Understanding how VSP dimers versus VSP monomers function is critical for being able to follow up other open questions in the field, like how lipids modulate VSP and even how we can use parts of VSP to create new tools like genetically encoded voltage indicators.” The biggest challenge of Kohout’s career thus far has been when her department at her previous institution was dis solved while she was going up for tenure. Her department was moved into another without much notice. She recalls, “We were told less than five minutes before a campus-wide email was sent announcing the decision. We were all stunned. Nothing in my training had prepared me for such an event. My department had supported me from the beginning of my time there, patiently answering all my questions from how to order equipment to how to be a good mentor, to how to be a good teacher and engage students in the classroom. They mentored me, advised me, helped me do experiments, shared resources with me; I can’t emphasize enough how much they helped my career, including getting tenure. Having that network complete ly dissolved from one day to another, for reasons that did not make sense to any of us, was very challenging. Many of those colleagues left after we were dissolved.” Kohout recounts, “While our ‘new’ department welcomed us, the entire situa tion left me feeling unsupported…I tried to make things work anyway. I volunteered for new departmental service, continued my established service, kept research going, acquired funding, kept teaching…overall tried to be a good citizen. But the sense that I didn’t matter at my institution never went away. I finally

October 2023

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