Deeper Dive
I have always been fascinated by how science can uncover stories about human life that would otherwise remain hidden. Growing up, this fascination drew me to archaeology and ancient Egypt, and to the dream of one day finding something hidden for thousands of years. I remember reading that through proteins preserved in ancient remains, scientists were able to discover evidence of inflammation and immune responses in our ancestors.
I found it extraordinary and, at the same time, puzzling. How could something so small carry traces of human life across millennia, yet something as subtle as a change in its shape contribute to devastating diseases like Alzheimer’s? How does a protein find its right shape in the first place?
The opportunity to work in a research lab to investigate these questions was a dream come true: a chance to uncover the mysterious journey a protein takes as it folds.
Using optical tweezers, I followed individual proteins as they folded and unfolded in real time and engineered the experimental system to identify which part of the protein was involved in each step. Across many proteins, I discovered a repeatable progression through three intermediate states, showing that folding is not a random event but a predictable, step-by-step pathway.
One of the first challenges I faced was noise. The changes in protein length I was measuring were only a few nanometers, making real folding events difficult to distinguish from experimental noise. After repeating the experiment several times to minimize errors, I realized that improving the data required making the molecular construct itself more stable. I redesigned the molecular attachments until I obtained cleaner, more stable measurements.
A second challenge was determining which part of the protein produced each intermediate state. To solve this, I engineered flexible loops between specific structural regions, allowing me to identify which areas were folding and determine their order.
Protein folding is fundamental to every biological function throughout our bodies, from the way we breathe to the way we think. When proteins misfold and aggregate, they can contribute to diseases including Alzheimer’s, metabolic disorders and blindness. My work identifies critical “checkpoints” in the folding process, revealing where and how folding can go wrong. Uncovering these pathways could ultimately help researchers develop more targeted strategies for preventing or treating diseases caused by protein misfolding.
Beyond human health, the same principles could help engineer synthetic proteins with new functions, such as breaking down pollutants or creating sustainable biomaterials. By decoding the rules that govern how proteins build themselves, I hope my work can contribute to better approaches to human disease and new biological solutions to some of our planet’s greatest challenges.