On a classroom projection screen, a cell biologist stood in a pond, wearing waders, and introduced his research on the inner workings of tiny freshwater amoebae. In footage he had captured under a microscope, materials streamed through their cells in coordinated, nonrandom patterns. This kind of real-time microscopic imaging was far less common in the 1970s than it is today, and for Margaret Titus, then an undergraduate at Smith College, the question came immediately: How do cells orchestrate such movement?
Now, as a professor in the Department of Genetics, Cell Biology, and Development, Titus continues to investigate that fundamental question. At the center of her work are myosins, tiny motor proteins that generate force within cells by moving along the actin filaments that make up the cytoskeleton. While myosin is best known for its role in muscle contraction, Titus focuses on a broader family of these proteins that help cells move, change shape, and transport materials.
“I think of myosin as a combustion engine,” she explains. “You can have it in your lawnmower. You can have it in a motorcycle. You can have it in your snowmobile, or, dare to dream, in a Maserati. The principles are the same, but what’s different is how you tune that motor.”
Titus is especially interested in a group of myosins that are calibrated to help cells sense and respond to their environment. At the cellular level, these roles depend on thin, finger-like projections called filopodia that extend beyond the cell surface, as well as more specialized structures such as microvilli in the intestine and stereocilia in the ear. “What we discovered many years ago is that one of these myosins is essential for making filopodia. If you don’t have this myosin, you don’t get filopodia,” she explains. “What that means is that you basically have a motor that’s making its own track.”
To study these processes, Titus uses the social amoeba Dictyostelium discoideum, a model organism that shares key cellular behaviors with human cells. These amoebae sense chemical signals and move toward them through chemotaxis, a process also central to immune responses and cancer spread. Because Dictyostelium can be genetically manipulated and exhibits clear cell movement, it provides a powerful system for understanding how cells move in response to external cues.
In addition to leading her research group, Titus has held several leadership positions in graduate education, including her current role as Associate Dean for Graduate Education and Postdocs. Her approach to mentorship is shaped by her own experiences as a trainee, including a postdoctoral advisor who encouraged her to think beyond biochemical questions and use molecular genetics to explore how myosins function within living cells.
“I think science shouldn’t be siloed,” she says. “If we want to understand what a myosin does, it’s not just what it does in the cell. You have to know biochemistry. You might need to know structural biology or cell physiology.” To foster this kind of interdisciplinary thinking, she helped build connections between the Biochemistry, Molecular Biology, and Biophysics (BMBB) and Molecular, Cellular, and Developmental Biology and Genetics (MCDB&G) graduate programs. These efforts led to the creation of a two-week orientation for incoming graduate students at Itasca Biological Station and Laboratories, where students build early relationships and networks that extend beyond their own labs.
Her research is now delving into questions in evolutionary cell biology, as she collaborates with colleagues to use a wider range of nontraditional model systems to understand how and when myosin function has evolved. Advances in imaging and experimental tools have also expanded what scientists can observe, far beyond what was possible in the classroom film that first sparked her interest. “Now you have a new array of tools, different organisms, different approaches,” she says. With those possibilities, she adds, students now have “almost no limits in what they want to do.” — Jonathan Damery