Rockefeller physicists create a “cell free” system capable of carrying out biological processes
BY LYNN LOVE
To physicists, a cell isn’t the ideal
place to do science.
Physics is a discipline based on concrete laws
and defined order, and the building blocks of life are messy and
unpredictable. That puts Albert
Libchaber, head of the Laboratory of
Experimental Condensed Matter Physics, in a prickly situation. He
studies, among other things, gene expression — which requires
Or, maybe, it doesn’t.
In what may be the initial step towards
building a “minimal cell,” Libchaber has designed the
first fully functional three gene network in vitro that processes
genetic input and manufactures proteins. Based entirely on
off-the-shelf biochemical components, this network is the first
step toward harnessing the informational process found in
“Biological researchers are adept at
reverse engineering the cell,” says Libchaber. “As
physicists studying biological systems, we are more interested in
forward engineering based on the laws of biology.”
Libchaber and his colleagues’ genetic
network, published recently in the Proceedings
of the National Academy of Sciences, is
analogous to a conventional electrical circuit — that of a
flashlight, for example. A cell-free extract is used as a battery
to carry out transcription and translation. RNA polymerase is the
input that drives expression of gene clones into plasmids, the
hardware of the system.
Output of the circuit is measured with reporter
proteins, the firefly luciferase or a green fluorescent protein.
Both are visible as either bioluminescent or fluorescent molecules
when viewed under a microscope.
Other scientists have developed single-gene
systems, but this is this first time a three-gene “cell
free” system has worked. The key to success,
Libchaber’s team discovered, is in carefully balancing
transcription chemistry against translation chemistry, an insight that paves the way for
Libchaber and his two postdoctoral associates, Vincent Noireux and
Roy Bar-Ziv, to combine synthetic gene expression with other
features of cellular function.
Next steps may include: artificial cell
membranes, followed by nanopores, to allow small molecules to move
through that membrane, and, ultimately, reproduction capabilities
for the tiny structures.
“Biology provides a great model for creating a self-replicating machine,”
says Libchaber. “Von Neumann proposed some mechanisms for it;
Watson and Crick revealed the basis for it. This type of research
is what physicists can do.”
Though cell-free protein synthesis is still
nascent, Libchaber’s genetic network demonstrates how
proteins could someday be manufactured far more efficiently and
precisely than current techniques allow, a prospect that has
far-reaching implications for the biotech industry.