Living well into advanced age is a true blessing — but one that is ever threatened by the looming risks of developing Alzheimer’s disease or other age-related dementia. Despite billions of dollars spent on finding a cure, Alzheimer’s continues unabated, claiming more and more lives in our aging population. But researchers like Graduate Center Professor Shana Elbaum-Garfinkle (Biochemistry), who is part of the Structural Biology Initiative at the Graduate Center’s Advanced Science Research Center (ASRC), are finding promising new paths to treatment.
The hope lies in breakthrough findings about proteins and cell structure made by Elbaum-Garfinkle and her colleagues.
Much lip service is given in science and other disciplines to the importance of interdisciplinary research. But Elbaum-Garfinkle — who majored in physics as an undergraduate at Hunter College, then studied biophysics and biochemistry as a Ph.D. student at Yale, and finally studied chemical and biochemical engineering as a postdoctoral fellow at Princeton — embodies it.
As a doctoral student, Elbaum-Garfinkle delved into disordered proteins, i.e., proteins with an unusually disordered molecular structure. They are known to form the plaques — also known as fibers or tangles — that are found in the brains of people with Alzheimer’s and other neurodegenerative diseases. She and her colleagues were trying to understand the proteins on a molecular level and so prevent their aggregation into fibers.
Three years ago, as a postdoc, Elbaum-Garfinkle made an important discovery: the same disordered proteins that turned into the fibers associated with Alzheimer’s also formed fluid-like, dynamic, reversible structures (for a visual, think of the globules in a lava lamp) that help our cells to function.
The finding, she said, “holds a tremendous amount of potential to open up new therapeutic directions and strategies.” The paper she published in PNAS (Proceedings of the National Academy of Sciences) has been cited more than 130 times. Equally exciting, at least three other papers published around the same time reported similar results, which further validated her work. (In a recent article in Nature, she reflected on the many papers published at the same time as hers. “We called it the flurry,” she said.)
Elbaum-Garfinkle explained, “If we can understand the rules that govern when the proteins form something liquid-like versus a fiber, we could perhaps avoid the fiber phase and keep things more fluid and dynamic instead of something that’s really undesirable.”
Inspired by the biomedical potential of her finding, she applied for a Pathway to Independence grant from the National Institutes of Health. She proposed that she would incorporate an organism — C. elegans, a 1 millimeter-long, transparent roundworm — into her work so that she could study the protein pathways in a living creature, not just the test tube. She would be the first person to look for the healthy, liquid-like phase of the proteins in the nervous system of a C. elegans.
She secured the competitive grant — about $1 million — to pursue this research, first as a mentored postdoc and, ultimately, as the head of her own lab.
Now, at the ASRC, Elbaum-Garfinkle is building out the lab she envisioned.
And, she said, she chose the right place to work. “It’s the place where my research program can really thrive because it’s very, very rare to have people with such diverse expertise — nanoscience, neuroscience, structural biology, environmental science, and photonics — in one building, meeting weekly. That never happens. Here, every week, every day, we’re cross-pollinating. For me, that was tremendous because I’ve always been at the interface of fields.”
Update: In an interview with Nature, Elbaum-Garfinkle spoke about the breakthroughs in cell biology involving phase separation (similar to oil droplets in water). “It’s a new paradigm that’s really transforming our understanding of cell biology as a whole,” she said. Read the article here.