When Dr. Weidong Yang, biological sciences, showed a movie at a recent conference of a single molecule passing through the nuclear pore complex of a cell, the audience of biologists, chemists and photochemical scientists gasped and exclaimed in surprise and recognition of the importance of what they had just witnessed. “This is something they had never seen before,” Yang said, smiling.
What he and his research team at BGSU have accomplished is indeed groundbreaking. Before they captured a moving, three-dimensional image of this critical transit through the cell’s gateway into the nucleus, it was unknown both how the nuclear transport system worked and what path materials and information took as they passed through the five-nanometer-wide opening.
Using single molecules of proteins they have rendered fluorescent with lasers and organic dyes, the team tracks the protein’s progress with a powerful microscope and high-speed, super-resolution camera.
“These innovative techniques need strong support,” said Yang, who has a joint appointment in photochemical sciences. His research is funded by a National Institutes of Health grant of $400,000 over three years. The funding has paid for major upgrades to his cell-biology and microscopy-imaging laboratories and the purchase of specialized equipment. The Ohio Board of Regents has also contributed to the study.
Graduate and undergraduate students in the lab are benefiting from the opportunity to work in this promising field. “Some of them have had offers to go to other schools when they graduate, but they don’t want to leave. They want to learn these new techniques. It makes them more competitive in finding jobs compared with those in pure physics or biology,” Yang said.
Yang’s work is gaining international attention. It will appear in five scientific journals this year, and the prestigious journal Proceedings of the National Academy of Sciences featured Yang and his post doctoral student Jiong Ma’s article on their work as its lead story in the April edition. Yang has been an invited speaker at several high-level conferences on single-molecule research, a leading new discipline that blends biology, chemistry and physics. “We can provide evidence to show we can do something other people can’t do. It’s new, it’s exciting, and we can do it,” he said enthusiastically.
The outside attention is coming because the discoveries are vitally important to research into the causes and treatment of disease. If the nuclear pore is not functioning properly, it can permit potentially dangerous materials into the nucleus. Dysfunctions of the nuclear transport system are linked to numerous human diseases including leukemias, cancers and liver cirrhosis.
“It’s a trafficking problem,” Yang said. “We want to control what the pore is letting in. These are problems that traditional biomedical measures cannot conquer. Now that we can capture the molecule in a pore, we can compare a normal cell to a cancer cell to see what changed, what’s different. Advances expected from this work will directly impact our understanding and development of therapies.”