Hunt's group hypothesized that polar ejection forces should be proportional to the chromosome's size, and therefore could be predictably changed by altering the size of the chromosomes. Using newts as a model organism, they cut off pieces of the chromosomes' arms.
"We asked what the relationship is between the size of the fragment we removed and the direction the chromosome moved," Hunt said. "Not only did we observe a relationship, we established that polar ejection forces were in fact a direct cue that guided chromosomal movements in mitosis."
To achieve this, Hunt performed "nanoscale surgery," as he calls it, taking advantage of the unprecedented precision of femtosecond pulses of laser light. A femtosecond is one billionth of one millionth of a second. The chromosomes he altered were only micrometers long, and the slices across the chromosomes were only nanometers thick. A nanometer is one-billionth of a meter, about a million times thinner than a human hair.
Understanding how chromosome guidance occurs allows scientists to determine how failures lead to genetic diseases, aging and cancer. When cells don't properly divide, they usually die. But survival can cause cancer or aging-related disorders. Likewise, genetic diseases such as Down's syndrome result from improper chromosome segregation.
Mitosis, Hunt says, is one of the most important targets of chemotherapy.
"By knowing how chromosomes move, we can better understand how these drugs interfere with those movements and we can design experiments to screen for new drugs," Hunt said. "It will also allow us to have a better handle on what makes these drugs work. There are a lot of drugs that interfere with mitosis, but only a few are good for cancer therapy."
|Contact: Nicole Casal Moore|
University of Michigan