2013 Annual Report - Jesus College - University of Cambridge

SYNTHETIC BIOLOGY I Jesus College Annual Report 2013 27
such as spots or stripes or, as demonstrated
in Turing’s original paper, the dappled
pattern of a cow. This mechanistic
explanation is extremely seductive as it is so
simple yet can explain so many of the
patterns we see in nature.
For much of the time since its publication,
Turing’s theory has been seen as something
of a “just so story” in its own right – it is a
mechanism that could produce the patterns
that we see and we like the story that it tells
but it is just a piece of mathematics. Is there
any evidence that biological molecules and
cells can actually function this way? Recently
there has been an increase in the number of
papers that combine experimental evidence
and modelling that suggest that Turing’s
mechanism may be functioning in a number
of developmental contexts. This evidence is
somewhat circumstantial, as biological
systems are extremely complex and
identifying the biochemical network that is
performing the specific functions of the
Turing-patterning within the baroque
elaborations that have been created by
evolution is extremely difficult.
There is another possibility, however. The
emerging field of synthetic biology gives us
the tools and the conceptual framework to
build genetic circuits out of DNA, run them
in microbes, and specifically test Turing’s
ideas divorced from the complexity and
historical contingency of naturally evolved
systems. Synthetic biology seeks to apply the
lessons learned from the field of engineering
to biology, creating libraries of wellcharacterized
genetic parts, assembling
those parts into devices, and creating
predictable systems out of those devices. By
building a working biological system that
creates pattern by Turing’s mechanism, we
can validate the model and examine the
properties of such a system. This will remove
Turing’s mechanism from the realm of the
“just so story” and show that it really can
function in a biological system.
With the tools of synthetic biology, we can
“paint” bacteria with fluorescent proteins, so
that we can observe them and, perhaps more
importantly, get them to paint themselves
based on the outputs of the circuit they are
running. As visible in the accompanying
figure, I have engineered bacteria to
independently send and receive two different
diffusible signals that have been adapted
from bacterial quorum sensing systems,
producing different coloured fluorescent
proteins in response to different signals. This
gives me the two morphogens required in
Turing’s mechanism. What remains is to wire
these signals together in the appropriate
positive and negative feedback loops (easier
said than done, of course) and then I will be
able to tell the story of how the bacteria make
their spots.
Bacteria respond to two different diffusing signals by
producing two different fluorescent proteins