Biology Reference
In-Depth Information
Further, it is in theory possible to create complex sequential logics by careful
positioning of recombinase recognition sites in the sequence.
Methodology/Principal Findings
In this work, we describe the design and synthesis of an inversion switch using
the fim and hin inversion recombination systems to create a heritable sequen-
tial memory switch. We have integrated the two inversion systems in an over-
lapping manner, creating a switch that can have multiple states. The switch is
capable of transitioning from state to state in a manner analogous to a finite
state machine, while encoding the state information into DNA. This switch
does not require protein expression to maintain its state, and “remembers” its
state even upon cell death. We were able to demonstrate transition into three
out of the five possible states showing the feasibility of such a switch.
Conclusions/Significance
We demonstrate that a heritable memory system that encodes its state into
DNA is possible, and that inversion recombination system could be a start-
ing point for more complex memory circuits. Although the circuit did not
fully behave as expected, we showed that a multi-state, temporal memory is
achievable.
introduction
Synthetic Biology aims to make the implantation of new, complex biological
function in cells more of an engineering science than a biology research project. A
central effort of this emerging field is the design of modular biological parts that
facilitate both the ease of manufacture and the design of predictable function in
cells. The hope is that this will allow applications at larger scale and with more
sophistication than is currently feasible with the more ad hoc genetic engineering
approaches commonly applied today. If successful, a great deal is to be gained
from this approach in supporting classical applications such as industrial expres-
sion of useful proteins, creation of pathways for biological synthesis of organic
molecules for pharmaceuticals and commodity natural products, or to confer a
simple phenotype such as pest or drought resistance on a host.
The field, however, looks forward to challenges in global health, energy and
the environment that could be well-served by carefully engineered microbes with
more complex “programming” to sense and respond to variable and uncertain
environments found beyond the bioreactor. Such applications might include, for
example, controlled, safety-assured deployment of engineered microorganisms to
remediate water and soils, support crop growth in marginal soil, treat disease,
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