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Engineer turns bacteria into living computers28 Apr
2005
In a
step toward making living cells function as if they were tiny
computers, engineers at Princeton have programmed bacteria to
communicate with each other and produce color-coded patterns.
The feat, accomplished in a biology lab within the
Department of Electrical Engineering, represents an important
proof-of-principle in an emerging field known as "synthetic
biology," which aims to harness living cells as workhorses
that detect hazards, build structures or repair tissues and
organs within the body.
"We are really moving beyond
the ability to program individual cells to programming a large
collection -- millions or billions -- of cells to do
interesting things," said Ron Weiss, an assistant professor of
electrical engineering and molecular biology.
Collaborating with researchers at the California
Institute of Technology, Weiss and graduate student Subhayu
Basu programmed E. coli bacteria to emit red or green
fluorescent light in response to a signal emitted from another
set of E. coli. In one experiment, the cells glowed green when
they sensed a higher concentration of the signal chemical and
red when they sensed a lower concentration. In a Petri dish,
they formed a bull's-eye pattern -- a green circle inside a
red one -- surrounding the sender cells.
In addition
to demonstrating that the genetic programming techniques work,
this sensing system could be useful for the detection of
chemicals or organisms in laboratory tests. "The bull's-eye
could tell you: This is where the anthrax is," said Weiss.
The researchers published their results in the April
28 issue of Nature. In addition to Weiss and Basu, authors of
the paper are postdoctoral researcher Yoram Gerchman at
Princeton and professor of chemical engineering Frances Arnold
and graduate student Cynthia Collins at Caltech. It was funded
by a grant from the U.S. Defense Advanced Research Projects
Agency.
In previous work, including a paper published
March 8 in the Proceedings of the National Academy of Sciences
along with Sara Hooshangi and Stephan Thiberge, Weiss showed
the feasibility of inserting engineered pieces of DNA into
cells to make them behave in the same manner as digital
circuits. The cells, for example, could be made to perform
basic mathematical logic and produce crisp, reliable readouts
that are more commonly associated with silicon chips than
biological organisms. The new paper applies similar techniques
to a large population of cells.
"Here we're showing an
integrated package where the cells have an ability to send
messages and other cells have the ability to act on these
messages," said Weiss.
The creation of patterns, such
as the bull's-eye effect, is a key step in one of Weiss'
eventual goals, which is to have the cells secrete materials
that build physical devices such as antennas or transmitters
in places that are hard for humans to reach. Programmed cells
also could be used to control the repair or construction of
tissues within the body, possibly guiding stem cells to the
locations where they are needed for the growth of new nerve or
bone cells in a process Weiss called "programmed tissue
engineering."
Even the early step of creating patterns
in a Petri dish, however, may be useful as a tool for other
scientists, particularly developmental biologists who are
trying to understand how the cells of an embryo arrange
themselves into patterns that become the various body parts of
a mature organism. In fruit fly embryos, for example, the
first cells are thought to differentiate into the head,
abdomen and other parts based on the concentration of chemical
signals that are emitted from the ends of the embryo.
In addition to conducting laboratory experiments,
Weiss and colleagues are creating computer models of their
engineered systems, which allow them to study how small
modifications would affect the ultimate behavior of the
organisms. So far, said Weiss, the experimental results have
matched the computer models fairly closely, but the goal is to
have a mathematically exact description of how each component
works.
"One of the nice things about synthetic biology
is that because we built the network from scratch, we should
be able to model all the important details," he said. At some
point in the future, he said, scientists will be able to
choose a behavior they want from cells, and a computer program
will create a genetic circuit to accomplish the task. "Then we
can do an experiment to see if the community of cells is
behaving as we desire. That is going to have a tremendous
number of applications."
Contact: Eric
Quinones
quinones@princeton.edu
609-258-5748
Princeton
University
http://www.princeton.edu/
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