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Programmable Cells: Engineer Turns Bacteria Into Living
Computers |
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Thursday, April 28 2005 @ 09:46 PM
CDT
Contributed by: Tommy
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 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." |
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