such as "Introduction", "Conclusion"..etc
Dec. 1, 2008 — The Stowers Institute's Rong
Li Lab has published findings that shed light on the ability of cells
to adapt to disruptions to their basic division machineries – findings
that may help explain how cancer cells elude the body's natural defense
mechanisms or chemotherapy treatment.
Working with yeast cells, the team disabled a motor protein, type II
myosin — which normally powers cell division — and observed the
cellular response. As predicted, blocking division initially resulted
in severe growth and cytokinesis defects. But after several selection
passages, some cells were able to solve the problems. Unexpectedly,
these cells ended up with more than the normal number of chromosomes.
The abnormal chromosome numbers led to changes in the patterns of gene
expression, which correlated with the cells' ability to evolve new ways
to complete division and resume growth.
"The ability of cellular systems to evolve is linked to their
component and network complexity, which allows the cell to develop
'workarounds' to salvage normal functions, even in times of crisis,"
said Giulia Rancati, Ph.D., Postdoctoral Research Associate and
co-equal lead author on the paper. "Surprisingly, the adaptation was
accomplished not by changes in DNA sequences but largely by modifying
the number of chromosomes in the cell (known as aneuploidy), which were
passed on to future generations."
The work was published in the November 26 issue of Cell.
"Another process that contributed to the successful adaptation
involved polyploidization, in which yeast cells multiplied their entire
set of chromosomes," said Norman Pavelka, Ph.D., Postdoctoral Research
Associate and co-equal lead author on the paper. "Aneuploidy and
polyploidy are hallmarks of cancer, and these findings suggest that
they may contribute directly to the ability of cancer cells to evolve,
allowing them to multiply, even as the body's natural mechanisms for
cellular regulation or chemotherapeutic drug treatment work to limit
The work establishes an exciting new path for the Rong Li Lab.
"These findings validated our view that evolvability is a trackable
and important subject for study," said Rong Li, Ph.D., Investigator and
senior author on the paper. "We are now working to determine whether
there are many distinct mechanisms of evolvability correlating with
varying types and degrees of cellular disruptions. Additionally, we
would like to explore the possibility of predicting the likely
evolutionary paths and outcomes based on the architecture of molecular
networks present in the cell; and in extending our research into
mammalian cell systems to directly study the role of aneuploidy in the
evolution of cancer."
Additional contributing authors from the Stowers Institute include
Brian Fleharty, Microarray Research Technician II; Aaron Noll,
Molecular Biology Programmer Analyst III; Rhonda Trimble, Histology
Specialist III; Kendra Walton, Molecular Biology Research Technician
III; Anoja Perera, Molecular Biology Lab Manager III; Karen
Staehling-Hampton, Ph.D., Managing Director of Molecular Biology; and
Chris Seidel, Ph.D., Managing Director of Microarray.
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