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Mathematical prediction of on-off switches in cell division proven

(Blacksburg, Va., Dec. 30, 2002) -- A team of Virginia Tech researchers has experimentally verified the predictions of a mathematical model concerning the regulation of irreversible transitions into and out of mitosis (the division of genetic material during the cell cycle). The commitment to mitosis must be an all-or-nothing decision; otherwise deleterious mutations result. This research highlights the power of pairing experimental and computational biology to understanding complex processes. Mathematical modeling of the cell cycle and other biological events may someday lead to previously unidentified targets for therapy of cancer and other diseases.

The article, "Hysteresis drives cell-cycle transitions in Xenopus Laevis egg extracts," will be published in the Proceedings of the National Academy of Sciences online edition the week of Dec. 30,2002 through Jan. 3, 2003 (article #02-5349 at www.pnas.org). It is the first collaborative publication between Virginia Tech biologists Jill Sible and John Tyson. Sible is corresponding author.

Tyson, a university distinguished professor, has been developing mathematical models to describe the cell cycle for many years, but only recently have experimentalists collaborated to test the validity of these models. His comprehensive model describing DNA synthesis and nuclear division in cell-free extracts from frog eggs was published in 1993.

In this project, the researchers set out to test predictions made by the mathematical model regarding specific levels of the protein cyclin required to regulate cell division, or mitosis. The experimental challenges were quantitative. "We had to be very precise," says Sible. "We found that, qualitatively and quantitatively, we were able to validate three key predictions of the model regarding the amount of cyclin required to start, maintain, and stop mitosis."

Cells enter mitosis by activating the enzyme Cdc2 and leave mitosis when Cdc2 activity drops. Cdc2 is
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Contact: Jill Sible
siblej@vt.edu
540-231-1842
Virginia Tech
30-Dec-2002


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