A way to coax cells to do natural
things under unnatural circumstances has been developed by computer scientist at Washington
University in St. Louis. This study could be useful for stem
cell research, gene therapy and biofuel production.
the Henry Edwin Sever Professor of Engineering in the School of
Engineering & Applied Science, has designed an algorithm, called
NetSurgeon, that recommends genes to surgically remove from a cell's
genome to force it to perform a normal activity in a different
environment or circumstance.
‘A computer scientist has developed a way to coax cells to do natural things under unnatural circumstances, which could be useful for stem cell research, gene therapy and biofuel production.’
For example, ordinary baker's yeast cells
normally produce a lot of alcohol, a biofuel, when fed sugar extracted
from the edible kernels of corn plants. NetSurgeon designed genetic
surgeries that convinced the cells to make more alcohol when fed a type
of sugar found in the inedible leaves and stalks.
The research is published in PNAS Early Edition
have been engineered to make alcohol out of xylose, a type of sugar
found in the woody parts of plants, but they don't do it very well,"
Brent says. "We think the problem is not that they can't do it, but that
they don't want to. So we have to convince them by making them use the
same set of genes they use when they're fed sugar from corn kernels. We
sometimes think about this as causing the yeast to 'hallucinate' that
they are in a sugar they like to turn into alcohol."
what we want to impact is the behavior of the cells and the ways they
respond to things," Brent says. "One of the ways they respond is by
changing the mix of cellular parts they are making. We're trying to
engineer the cells to change the mix of parts to do something associated
with desirable behaviors, like becoming a liver cell or producing a
biofuel. We call this 'transcriptome engineering,' because it changes
the control circuits in order to change the production of many parts at
once, rather than focusing on one part at a time."
research group focuses transcriptional regulatory networks, the control
circuits by which cells sense their situation and respond to it by
changing how much protein is made from each gene. The key components of
these networks are transcription factors, or proteins that turn genes on
and off. NetSurgeon takes in the current production level from each
gene and the goal level and suggest transcription factors to remove, by
deleting the genes that encode them, in order to move production levels
toward the goals.
"If you have a
stem cell and want it to be a liver cell, you want to cause it to turn
its genes up and down to match the levels found in a liver cell," Brent
While Brent's lab has
been studying the way yeast responds to excess sugar, Brent says this
technique can be applied to any organism.
"Many of the same circuits exist in human cells and are even drug targets," he says.