It often feels like science today moves at the speed of light. Every week, a new model, algorithm, or “paradigm shift” captures attention. Papers are published faster than they can be read, and young researchers are told, almost reflexively, that novelty is everything. In such a climate, choosing to work on something as old and familiar as the alpha helix can feel almost rebellious.

When I tell people that I study alpha-helical membrane proteins, I often get a curious look: the kind that says, “But haven’t we already solved that?”. After all, the alpha helix was first described by Linus Pauling in 1951 and has since become one of the most recognizable motifs in molecular biology. It’s in every textbook, in every introductory biochemistry lecture.

But I kept coming back to them with another question: If the alpha helix is so well understood, why do we still find new behavior every time we look closer?

As I’ve learned through my own research, even the most “complete” structures still have stories left to tell. Through computational modeling and evolutionary analysis, I found that even small changes (substitutions that alter polarity or truncations that disrupt symmetry) can reshape the very dynamics of bio-assembly (Karagöl et al. 2024a, Karagöl et al. 2024b, Sajeev-Sheeja et al. 2025, Karagöl 2025a). These are not trivial effects; they are clues to how nature reuses and redefines ancient structural solutions. In that realization, I found peace in slowing down, in studying something deeply, not quickly.

My focus is on how subtle evolutionary changes, such as hydrophobic substitutions and QTY-based transformations, influence alpha-helical assembly and oligomerization. The deeper I went, the more I realized that even in a field as mature as alpha-helical biology, there are spaces where new insight can thrive. The patterns are ancient, but the context (the evolution, the membrane environment, the isoform variation) constantly shifts (Karagöl et al. 2024c, Karagöl et al 2025b).

Standing on the shoulders of giants

I have been fortunate to work under the mentorship of Professor Shuguang Zhang at the Massachusetts Institute of Technology: a scientist whose discoveries in peptide self-assembly have influenced countless areas of research. Professor Zhang’s own mentor was Alex Rich, one of the great pioneers of structural biology and the discovery of the nucleic acid double helix.

Sometimes I think about that lineage: Pauling to Rich to Zhang, and now, in some small way, to me. It’s humbling. And it reminds me that science isn’t just about novelty. It’s about continuity, about understanding how ideas evolve across generations and how curiosity never really grows old.

Professor Zhang encouraged me not to shy away from “old” topics. Instead, he challenged me to see them differently. He reminded me that rediscovery is a form of discovery, and that working on a classic subject doesn’t make your work less relevant, it can make it more enduring. In our discussions, he often spoke about the elegance of simple ideas, about how the most profound insights often emerge from things we thought we already knew. His mentorship taught me that science is not a race to be first, but a long, shared conversation that stretches across generations.

Lessons from the helix

The alpha helix itself feels symbolic of the scientific journey. It turns steadily, rising with each rotation: repeating, yet always moving forward. As an early-career researcher, that rhythm feels familiar. The daily experiments, the failed models, the moments of quiet clarity, all are part of a spiral that, over time, climbs toward understanding.

Working on alpha helices has taught me patience and humility. It reminded me that “well-studied” does not mean “fully understood”. There is room for curiosity even in the most established of systems.