Stop-motion pictures
Ulrike Eggert uses small molecules to trace the sequence of cell division, shown in the image below.
Although it is described in every high school biology textbook, the process of cell division — cytokinesis — remains in many respects a mystery. In preparation for division, cells duplicate and divide their DNA, then form a ring at their center. The ring tightens until a new cell pinches off from the old one. Many of the details of the process, however, are unclear, because it is both very complicated and very fast — about 45 minutes from start to finish.
Ulrike Eggert, PhD, who joined Dana-Farber last year at the same time as fellow chemical biologist Nathanael Gray, PhD, is using small molecules to halt cytokinesis at key points, creating freeze-frame pictures of dividing cells and revealing how their proteins change each step of the way.
"It's surprising how little we know about cell division, considering that it's one of the most basic biological processes," says Eggert, whose laboratory is alongside Gray's at Harvard Medical School. "Small molecules can bring the process to a stop very quickly. Within a few seconds you can see them working."
"It's surprising how little we know about cell division, considering that it's one of the most basic biological processes."
As a postdoctoral fellow at Harvard Medical School and now as a Dana-Farber faculty member, Eggert has built a library of such cytokinesis-stoppers. She began by screening 50,000 candidate compounds, found 50 that had the desired effect, and chose the 25 most promising ones to study. The small molecules freeze the division process at different stages by binding to different cell proteins.
The challenge now is to identify each of these target proteins within the cell. Eggert first used a technique called RNA interference, which stifles the production of specific proteins, to screen for proteins that play a role in cell division. She then treated cells with small molecules and compared the results of the two approaches. If small molecules and RNA interference produced a similar effect, it suggested that the same proteins were involved. Eggert is currently studying four small molecules known to inhibit cell division and plans to use them to understand how division takes place and how it goes out of control in many cancers.
"If we can show that one of these molecules blocks a specific protein in the pathway," Eggert explains, "that protein would be a natural target for drug therapy."
- Next: Wedge site story
- Page: 1 | 2 | 3 | 4
